Comprehensive analysis of iron utilization by Mycobacterium tuberculosis

Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobacti...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PLoS pathogens Jg. 16; H. 2; S. e1008337
Hauptverfasser: Zhang, Lei, Hendrickson, R. Curtis, Meikle, Virginia, Lefkowitz, Elliot J., Ioerger, Thomas R., Niederweis, Michael
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 18.02.2020
Public Library of Science (PLoS)
Schlagworte:
Amide Synthases - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Transport
Biology and Life Sciences
Chromosomes
Efflux
Genetic research
Glycosylated hemoglobin
Heme
Heme - metabolism
Hemoglobin
Hemoglobins
Hemoglobins - metabolism
Humans
Infections
Iron
Iron - metabolism
Medicine and Health Sciences
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mutants
Mutation
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - metabolism
Novels
Oxazoles - metabolism
Pathogenic microorganisms
Physiological aspects
Proteins
Research and Analysis Methods
Secretion
Siderophores
Siderophores - metabolism
Software
Transcription
Transcription (Genetics)
Transposon mutagenesis
Transposons
Tuberculosis
Utilization
Virulence
Alabama
United States > US
Texas
ISSN:1553-7374, 1553-7366, 1553-7374
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Abstract Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.
AbstractList Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.
Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology. Tuberculosis is caused by Mycobacterium tuberculosis and is the leading cause of death from a single infectious disease, resulting in approximately 1.5 million deaths per year worldwide. M. tuberculosis resides in granulomas which are formed in the lung in an attempt to wall off the infection. Recently, it was shown that iron-sequestering proteins accumulate in these granulomas to high concentrations, establishing an environment devoid of free iron. In this study, we examined the contribution of each gene towards the utilization of different iron sources by M. tuberculosis. We identified 165 genes involved in iron utilization by Mtb, 66 of which were classified as essential or as required for optimal growth of M. tuberculosis in the presence of different iron sources. Our study provides an unprecedented insight into the genetic determinants of iron utilization by M. tuberculosis.
Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.
Audience Academic
Author Lefkowitz, Elliot J.
Meikle, Virginia
Niederweis, Michael
Hendrickson, R. Curtis
Ioerger, Thomas R.
Zhang, Lei
AuthorAffiliation 2 Department of Computer Science and Engineering, Texas A&M University, College Station, Texas, United States of America
1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
National Institutes of Health, UNITED STATES
AuthorAffiliation_xml – name: 1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
– name: National Institutes of Health, UNITED STATES
– name: 2 Department of Computer Science and Engineering, Texas A&M University, College Station, Texas, United States of America
Author_xml – sequence: 1
  givenname: Lei
  surname: Zhang
  fullname: Zhang, Lei
– sequence: 2
  givenname: R. Curtis
  orcidid: 0000-0001-6986-4630
  surname: Hendrickson
  fullname: Hendrickson, R. Curtis
– sequence: 3
  givenname: Virginia
  orcidid: 0000-0003-3469-7232
  surname: Meikle
  fullname: Meikle, Virginia
– sequence: 4
  givenname: Elliot J.
  orcidid: 0000-0002-4748-4925
  surname: Lefkowitz
  fullname: Lefkowitz, Elliot J.
– sequence: 5
  givenname: Thomas R.
  surname: Ioerger
  fullname: Ioerger, Thomas R.
– sequence: 6
  givenname: Michael
  orcidid: 0000-0003-4068-8092
  surname: Niederweis
  fullname: Niederweis, Michael
BackLink https://www.ncbi.nlm.nih.gov/pubmed/32069330$$D View this record in MEDLINE/PubMed
BookMark eNqVkl2L1DAUhousuB_6D0QL3ujFjEnTJqkXwjKoO7Aq-HEd8jmboW26Sbo4_nrTnY5sl0WQXvSQPO97Tg7vaXbUuU5n2XMIlhAR-HbrBt_xZtn3PC4hABQh8ig7gVWFFgSR8uhOfZydhrAFoIQI4ifZMSoArhECJ9nFyrW911e6C_ZG5zw57oINuTO59a7Lh2gb-5tHm2qxyz_vpBNcRu3t0OZxENrLoXFJ8TR7bHgT9LPpf5b9_Pjhx-picfn103p1frmQGMO40GUNTVVIXBkoVZGqupTUUCooFAILaWoFSyAFrZRGQBKFVVUDRAula1FidJa93Pv2qS2blhBYgQghoAIIJGK9J5TjW9Z723K_Y45bdnvg_IZxH61sNOOYiwLykmOASmkINQqTAtG0KVxTIZPX-6nbIFqtpO6i583MdH7T2Su2cTcszUJRiZLB68nAu-tBh8haG6RuGt5pN4xzV7SidQHGuV_dQx9-3URteHqA7YxLfeVoys4xrAjEBRjbLh-g0qd0a2UKkrHpfCZ4MxMkJupfccOHENj6-7f_YL_M2Rd3F_h3c4cEJuDdHpDeheC1YdLG27yliW3DIGBj3A-7YGPc2RT3JC7viQ_-_5T9AY1rBIA
CitedBy_id crossref_primary_10_1093_femsre_fuab050
crossref_primary_10_3389_fmicb_2020_582582
crossref_primary_10_1038_s41467_021_26941_1
crossref_primary_10_1128_jb_00212_22
crossref_primary_10_1016_j_chembiol_2023_12_002
crossref_primary_10_3389_fimmu_2021_696491
crossref_primary_10_1099_mgen_0_001022
crossref_primary_10_3390_biom12030376
crossref_primary_10_1515_hsz_2022_0192
crossref_primary_10_1111_mmi_15314
crossref_primary_10_1128_AAC_00956_21
crossref_primary_10_1093_mtomcs_mfae011
crossref_primary_10_3389_fmicb_2022_956602
crossref_primary_10_1073_pnas_2112608119
crossref_primary_10_1128_spectrum_03604_22
crossref_primary_10_1007_s00018_021_04110_3
crossref_primary_10_1128_msphere_00389_22
crossref_primary_10_3390_microorganisms11061495
crossref_primary_10_1016_j_ijmm_2021_151495
crossref_primary_10_1016_j_gene_2020_145091
crossref_primary_10_1128_spectrum_01069_23
crossref_primary_10_3389_fcimb_2025_1556688
crossref_primary_10_1016_j_ijbiomac_2021_06_126
crossref_primary_10_1016_j_it_2025_02_009
crossref_primary_10_3390_M1806
crossref_primary_10_3389_fmicb_2024_1345389
crossref_primary_10_3390_medicina60111891
crossref_primary_10_1371_journal_ppat_1011650
crossref_primary_10_1016_j_micinf_2023_105239
crossref_primary_10_1111_mmi_15055
crossref_primary_10_1111_mmi_15370
crossref_primary_10_1111_crj_13677
crossref_primary_10_1128_aac_01629_22
crossref_primary_10_1128_msphere_00358_23
crossref_primary_10_1007_s11357_023_01048_1
crossref_primary_10_1128_spectrum_00118_22
crossref_primary_10_3390_pharmaceutics15020502
crossref_primary_10_1016_j_biochi_2024_06_006
crossref_primary_10_1038_s41579_021_00560_5
crossref_primary_10_1038_s41467_024_55136_7
crossref_primary_10_1093_ofid_ofab192
crossref_primary_10_1111_cmi_13253
crossref_primary_10_1128_mSystems_00673_21
crossref_primary_10_1128_spectrum_00487_24
crossref_primary_10_1126_sciadv_adx1129
crossref_primary_10_3389_fcimb_2022_1004148
crossref_primary_10_3390_microorganisms9020414
crossref_primary_10_3390_pathogens11090953
crossref_primary_10_1371_journal_pbio_3002874
crossref_primary_10_3389_fimmu_2021_665785
crossref_primary_10_1038_s41467_022_29873_6
crossref_primary_10_1016_j_tube_2023_102346
crossref_primary_10_1128_spectrum_02623_22
crossref_primary_10_1128_spectrum_01790_24
crossref_primary_10_1080_02648725_2022_2076031
crossref_primary_10_1093_jac_dkaf106
crossref_primary_10_3389_fcimb_2024_1480076
crossref_primary_10_1128_spectrum_02415_24
crossref_primary_10_1038_s41467_021_26925_1
crossref_primary_10_3389_fmicb_2025_1539139
crossref_primary_10_1038_s41467_025_56888_6
Cites_doi 10.1128/mBio.01092-17
10.1021/acsinfecdis.6b00095
10.1016/j.chom.2013.04.010
10.1186/1741-7007-8-49
10.1016/j.vaccine.2006.05.097
10.1128/IAI.00131-17
10.1038/s41467-019-12109-5
10.1186/1471-2105-14-303
10.1038/35042073
10.1016/j.bbamcr.2013.11.003
10.1371/journal.ppat.1002946
10.1128/IAI.70.7.3371-3381.2002
10.1371/journal.pcbi.1004401
10.1128/AAC.00037-14
10.1016/j.resmic.2003.11.009
10.1007/978-1-4939-2398-4_6
10.1073/pnas.0900589106
10.1099/13500872-142-8-2207
10.1084/jem.183.4.1527
10.1128/JB.01190-06
10.1002/pmic.200600853
10.1371/journal.pone.0078351
10.1128/mBio.01720-16
10.1371/journal.ppat.1002251
10.1073/pnas.0709530105
10.1111/mmi.13675
10.1039/C5MT90021B
10.1128/IAI.71.7.4159-4162.2003
10.1073/pnas.92.11.5189
10.1128/BR.34.2.99-125.1970
10.1046/j.1365-2958.2003.03425.x
10.1101/gr.092759.109
10.1016/j.tube.2010.09.008
10.1371/journal.pone.0102135
10.1128/JB.01921-07
10.1073/pnas.1311402111
10.1016/j.cbpa.2013.12.014
10.1073/pnas.1303674110
10.1016/j.celrep.2013.10.031
10.1016/j.tube.2008.08.003
10.1128/IAI.00229-12
10.1016/S1074-5521(98)90291-5
10.1038/nchembio717
10.1042/bj1910095
10.1074/jbc.M113.473371
10.1016/j.chom.2007.03.001
10.1016/j.smim.2014.09.009
10.1016/S0005-2736(02)00663-6
10.1042/bj0970166
10.1042/bj0940160
10.1038/ncomms5730
10.1128/mBio.02133-16
10.1111/mmi.12441
10.3389/fcimb.2017.00245
10.1128/JB.188.2.424-430.2006
10.3389/fcimb.2013.00080
10.1128/IAI.00613-10
10.3389/fcimb.2019.00081
10.1074/jbc.M209768200
10.1016/j.tube.2003.08.012
10.1084/jem.184.4.1349
10.1073/pnas.1523321113
10.1128/IAI.00540-18
10.1073/pnas.1400136111
10.1074/jbc.M112.448399
10.1021/bi2018305
10.1186/1472-6807-3-6
10.1128/JB.00223-09
10.1128/IAI.73.6.3492-3501.2005
10.1111/j.1600-065X.2010.00984.x
10.1023/A:1016710810701
10.1016/j.tim.2006.05.006
10.1084/jem.20041429
10.1371/journal.ppat.1003120
10.1039/C7MT00116A
10.1128/JB.01090-13
10.1128/JB.01312-10
10.1073/pnas.1009516108
10.1128/JB.187.16.5658-5664.2005
ContentType Journal Article
Copyright COPYRIGHT 2020 Public Library of Science
2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2020 Zhang et al 2020 Zhang et al
Copyright_xml – notice: COPYRIGHT 2020 Public Library of Science
– notice: 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2020 Zhang et al 2020 Zhang et al
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
ISN
ISR
3V.
7QL
7U9
7X7
7XB
88E
8FE
8FH
8FI
8FJ
8FK
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
DWQXO
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7P
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
7X8
5PM
DOA
DOI 10.1371/journal.ppat.1008337
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Canada
Gale In Context: Science
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Virology and AIDS Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Journals
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest One Sustainability (subscription)
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Central
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Biological Sciences
ProQuest Health & Medical Collection
PML(ProQuest Medical Library)
Biological Science Database
ProQuest Central Premium
ProQuest One Academic
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic (retired)
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
ProQuest Health & Medical Research Collection
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Health & Medical Research Collection
Biological Science Collection
AIDS and Cancer Research Abstracts
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList Publicly Available Content Database


MEDLINE


MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: PIMPY
  name: ProQuest Publicly Available Content
  url: http://search.proquest.com/publiccontent
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
DocumentTitleAlternate Iron utilization by Mycobacterium tuberculosis
EISSN 1553-7374
ExternalDocumentID 2377705030
oai_doaj_org_article_a6ab21a4a6034cf78fd67238004698bc
PMC7058343
A615716203
32069330
10_1371_journal_ppat_1008337
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GeographicLocations Alabama
United States--US
Texas
GeographicLocations_xml – name: Alabama
– name: Texas
– name: United States--US
GrantInformation_xml – fundername: NCI NIH HHS
  grantid: P30 CA008748
– fundername: NIAID NIH HHS
  grantid: R01 AI137338
– fundername: NCI NIH HHS
  grantid: P30 CA013148
– fundername: NCATS NIH HHS
  grantid: UL1 TR003096
– fundername: ;
  grantid: AI137338
GroupedDBID ---
123
29O
2WC
53G
5VS
7X7
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABUWG
ACCTH
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
AEAQA
AENEX
AEUYN
AFFHD
AFKRA
AFPKN
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AOIJS
B0M
BAIFH
BAWUL
BBNVY
BBTPI
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAP
EAS
EBD
EMK
EMOBN
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAO
IHR
INH
INR
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
MM.
O5R
O5S
OK1
OVT
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PJZUB
PPXIY
PQGLB
PQQKQ
PROAC
PSQYO
PV9
QF4
QN7
RNS
RPM
RZL
SV3
TR2
TUS
UKHRP
WOW
~8M
ADRAZ
CGR
CUY
CVF
ECM
EIF
H13
IPNFZ
NPM
RIG
WOQ
3V.
7QL
7U9
7XB
8FK
AZQEC
C1K
DWQXO
GNUQQ
H94
K9.
PKEHL
PQEST
PQUKI
PRINS
7X8
PUEGO
5PM
AAPBV
ABPTK
M~E
ID FETCH-LOGICAL-c661t-e491f52c65f1cd252c94c8f88b81bb6bcf9d140cb85de30c7d6d590382de9b463
IEDL.DBID M7P
ISICitedReferencesCount 67
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000518637800007&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 1553-7374
1553-7366
IngestDate Sun Aug 06 00:38:03 EDT 2023
Mon Nov 10 04:34:30 EST 2025
Tue Nov 04 01:57:11 EST 2025
Fri Sep 05 06:39:55 EDT 2025
Sat Nov 29 14:53:37 EST 2025
Tue Nov 11 10:32:43 EST 2025
Tue Nov 04 17:47:17 EST 2025
Thu Nov 13 14:46:56 EST 2025
Thu Nov 13 14:25:40 EST 2025
Mon Jul 21 06:05:24 EDT 2025
Sat Nov 29 05:43:10 EST 2025
Tue Nov 18 22:28:34 EST 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 2
Language English
License This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c661t-e491f52c65f1cd252c94c8f88b81bb6bcf9d140cb85de30c7d6d590382de9b463
Notes new_version
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
The authors have declared that no competing interests exist.
ORCID 0000-0001-6986-4630
0000-0002-4748-4925
0000-0003-4068-8092
0000-0003-3469-7232
OpenAccessLink https://www.proquest.com/docview/2377705030?pq-origsite=%requestingapplication%
PMID 32069330
PQID 2377705030
PQPubID 1436335
ParticipantIDs plos_journals_2377705030
doaj_primary_oai_doaj_org_article_a6ab21a4a6034cf78fd67238004698bc
pubmedcentral_primary_oai_pubmedcentral_nih_gov_7058343
proquest_miscellaneous_2358589200
proquest_journals_2377705030
gale_infotracmisc_A615716203
gale_infotracacademiconefile_A615716203
gale_incontextgauss_ISR_A615716203
gale_incontextgauss_ISN_A615716203
pubmed_primary_32069330
crossref_citationtrail_10_1371_journal_ppat_1008337
crossref_primary_10_1371_journal_ppat_1008337
PublicationCentury 2000
PublicationDate 20200218
PublicationDateYYYYMMDD 2020-02-18
PublicationDate_xml – month: 2
  year: 2020
  text: 20200218
  day: 18
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PLoS pathogens
PublicationTitleAlternate PLoS Pathog
PublicationYear 2020
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References EP Skaar (ppat.1008337.ref005) 2015; 7
R Pandey (ppat.1008337.ref031) 2012; 80
I Matsunaga (ppat.1008337.ref052) 2004; 200
KC Chinta (ppat.1008337.ref077) 2018; 25
C Ratledge (ppat.1008337.ref006) 2004; 84
PA Zunszain (ppat.1008337.ref063) 2003; 3
M Caza (ppat.1008337.ref075) 2013; 3
R Prados-Rosales (ppat.1008337.ref015) 2014; 196
NC Andrews (ppat.1008337.ref003) 2000; 1
KD Krewulak (ppat.1008337.ref029) 2011; 89
A Viljoen (ppat.1008337.ref048) 2017; 104
GM Rodriguez (ppat.1008337.ref007) 2006; 14
GA Snow (ppat.1008337.ref022) 1970; 34
LA Mike (ppat.1008337.ref071) 2013; 110
O Danilchanka (ppat.1008337.ref081) 2014; 111
LL Anzaldi (ppat.1008337.ref070) 2010; 78
VM Boradia (ppat.1008337.ref034) 2014; 5
M Krzywinski (ppat.1008337.ref043) 2009; 19
CM Jones (ppat.1008337.ref023) 2011; 193
JE Cassat (ppat.1008337.ref004) 2013; 13
CM Jones (ppat.1008337.ref013) 2014; 111
GM Rodriguez (ppat.1008337.ref072) 2002; 70
J Gobin (ppat.1008337.ref009) 1996; 183
T Cortes (ppat.1008337.ref054) 2013; 5
J Gobin (ppat.1008337.ref008) 1995; 92
A Serafini (ppat.1008337.ref018) 2013; 8
A Maciag (ppat.1008337.ref050) 2007; 189
YJ Zhang (ppat.1008337.ref041) 2012; 8
H Contreras (ppat.1008337.ref058) 2014; 19
GA Snow (ppat.1008337.ref020) 1965; 97
RR Crichton (ppat.1008337.ref001) 2001; 14
CC Wright (ppat.1008337.ref059) 2017; 85
A Mitra (ppat.1008337.ref026) 2017; 8
JM Lew (ppat.1008337.ref044) 2011; 91
C Ratledge (ppat.1008337.ref079) 1996; 142
MA DeJesus (ppat.1008337.ref080) 2013; 14
H Malen (ppat.1008337.ref053) 2007; 7
CP Owens (ppat.1008337.ref065) 2012; 51
C Hoffmann (ppat.1008337.ref028) 2008; 105
DL Stauff (ppat.1008337.ref066) 2008; 190
GM Rodriguez (ppat.1008337.ref010) 2006; 188
K Andries (ppat.1008337.ref056) 2014; 9
RC Hartkoorn (ppat.1008337.ref055) 2014; 58
S Nambu (ppat.1008337.ref064) 2013; 288
MA DeJesus (ppat.1008337.ref045) 2015; 11
P Domenech (ppat.1008337.ref047) 2005; 73
H Malhotra (ppat.1008337.ref035) 2017; 7
K Kurthkoti (ppat.1008337.ref033) 2017; 8
OR Homann (ppat.1008337.ref046) 2010; 8
IM Orme (ppat.1008337.ref076) 2014; 26
MB Ryndak (ppat.1008337.ref011) 2010; 192
CM Sassetti (ppat.1008337.ref051) 2003; 48
RM Wells (ppat.1008337.ref012) 2013; 9
S Puig (ppat.1008337.ref002) 2017; 9
R Pandey (ppat.1008337.ref032) 2014; 91
DL Clemens (ppat.1008337.ref037) 1996; 184
VJ Torres (ppat.1008337.ref068) 2007; 1
GA Snow (ppat.1008337.ref021) 1965; 94
SA Pacheco (ppat.1008337.ref060) 2013; 288
LE Quadri (ppat.1008337.ref061) 1998; 5
M Luo (ppat.1008337.ref014) 2005; 1
A Mitra (ppat.1008337.ref036) 2019; 10
EE Wyckoff (ppat.1008337.ref067) 2005; 187
JE Long (ppat.1008337.ref040) 2015; 1279
EN Houben (ppat.1008337.ref016) 2014; 1843
O Olakanmi (ppat.1008337.ref038) 2002; 277
MS Siegrist (ppat.1008337.ref017) 2009; 106
LJ Runyen-Janecky (ppat.1008337.ref025) 2013; 3
VK Sambandamurthy (ppat.1008337.ref078) 2006; 24
JE Griffin (ppat.1008337.ref039) 2011; 7
MA DeJesus (ppat.1008337.ref042) 2017; 8
PA Adams (ppat.1008337.ref062) 1980; 191
JM Tufariello (ppat.1008337.ref019) 2016; 113
A Milano (ppat.1008337.ref069) 2004; 155
JM Belardinelli (ppat.1008337.ref082) 2016; 2
DG Russell (ppat.1008337.ref073) 2011; 240
A Milano (ppat.1008337.ref057) 2009; 89
KL Richard (ppat.1008337.ref074) 2019; 9
MV Tullius (ppat.1008337.ref024) 2011; 108
MV Tullius (ppat.1008337.ref027) 2019; 87
RD Perry (ppat.1008337.ref030) 2003; 71
M Montoya (ppat.1008337.ref049) 2003; 1609
References_xml – volume: 8
  start-page: e01092
  year: 2017
  ident: ppat.1008337.ref033
  article-title: The capacity of Mycobacterium tuberculosis to survive iron starvation might enable it to persist in iron-deprived microenvironments of human granulomas
  publication-title: MBio
  doi: 10.1128/mBio.01092-17
– volume: 2
  start-page: 702
  year: 2016
  ident: ppat.1008337.ref082
  article-title: Structure-Function Profile of MmpL3, the Essential Mycolic Acid Transporter from Mycobacterium tuberculosis
  publication-title: ACS Infect Dis
  doi: 10.1021/acsinfecdis.6b00095
– volume: 13
  start-page: 509
  year: 2013
  ident: ppat.1008337.ref004
  article-title: Iron in infection and immunity
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2013.04.010
– volume: 8
  start-page: 49
  year: 2010
  ident: ppat.1008337.ref046
  article-title: MochiView: versatile software for genome browsing and DNA motif analysis
  publication-title: BMC Biol
  doi: 10.1186/1741-7007-8-49
– volume: 25
  start-page: 1938
  year: 2018
  ident: ppat.1008337.ref077
  article-title: Microanatomic Distribution of Myeloid Heme Oxygenase-1 Protects against Free Radical-Mediated Immunopathology
  publication-title: Human Tuberculosis. Cell Rep
– volume: 24
  start-page: 6309
  year: 2006
  ident: ppat.1008337.ref078
  article-title: Mycobacterium tuberculosis DRD1 DpanCD: a safe and limited replicating mutant strain that protects immunocompetent and immunocompromised mice against experimental tuberculosis
  publication-title: Vaccine
  doi: 10.1016/j.vaccine.2006.05.097
– volume: 85
  start-page: e00131
  year: 2017
  ident: ppat.1008337.ref059
  article-title: The Mycobacterium tuberculosis MmpL11 Cell Wall Lipid Transporter Is Important for Biofilm Formation, Intracellular Growth, and Nonreplicating Persistence
  publication-title: Infect Immun
  doi: 10.1128/IAI.00131-17
– volume: 10
  start-page: 4260
  year: 2019
  ident: ppat.1008337.ref036
  article-title: Heme and hemoglobin utilization by Mycobacterium tuberculosis
  publication-title: Nat Commun
  doi: 10.1038/s41467-019-12109-5
– volume: 14
  start-page: 303
  year: 2013
  ident: ppat.1008337.ref080
  article-title: A Hidden Markov Model for identifying essential and growth-defect regions in bacterial genomes from transposon insertion sequencing data
  publication-title: BMC Bioinformatics
  doi: 10.1186/1471-2105-14-303
– volume: 1
  start-page: 208
  year: 2000
  ident: ppat.1008337.ref003
  article-title: Iron homeostasis: insights from genetics and animal models
  publication-title: Nat Rev Genet
  doi: 10.1038/35042073
– volume: 1843
  start-page: 1707
  year: 2014
  ident: ppat.1008337.ref016
  article-title: Take five—Type VII secretion systems of mycobacteria
  publication-title: Biochim Biophys Acta
  doi: 10.1016/j.bbamcr.2013.11.003
– volume: 8
  start-page: e1002946
  year: 2012
  ident: ppat.1008337.ref041
  article-title: Global assessment of genomic regions required for growth in Mycobacterium tuberculosis
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1002946
– volume: 70
  start-page: 3371
  year: 2002
  ident: ppat.1008337.ref072
  article-title: IdeR, an essential gene in Mycobacterium tuberculosis: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response
  publication-title: Infect Immun
  doi: 10.1128/IAI.70.7.3371-3381.2002
– volume: 11
  start-page: e1004401
  year: 2015
  ident: ppat.1008337.ref045
  article-title: TRANSIT—A Software Tool for Himar1 TnSeq Analysis
  publication-title: PLoS Comput Biol
  doi: 10.1371/journal.pcbi.1004401
– volume: 58
  start-page: 2979
  year: 2014
  ident: ppat.1008337.ref055
  article-title: Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis
  publication-title: Antimicrob Agents Chemother
  doi: 10.1128/AAC.00037-14
– volume: 155
  start-page: 192
  year: 2004
  ident: ppat.1008337.ref069
  article-title: The Mycobacterium tuberculosis Rv2358-furB operon is induced by zinc
  publication-title: Res Microbiol
  doi: 10.1016/j.resmic.2003.11.009
– volume: 1279
  start-page: 79
  year: 2015
  ident: ppat.1008337.ref040
  article-title: Identifying Essential Genes in Mycobacterium tuberculosis by Global Phenotypic Profiling
  publication-title: Methods Mol Biol
  doi: 10.1007/978-1-4939-2398-4_6
– volume: 106
  start-page: 18792
  year: 2009
  ident: ppat.1008337.ref017
  article-title: Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0900589106
– volume: 142
  start-page: 2207
  year: 1996
  ident: ppat.1008337.ref079
  article-title: The occurrence of carboxymycobactin, the siderophore of pathogenic mycobacteria, as a second extracellular siderophore in Mycobacterium smegmatis
  publication-title: Microbiology
  doi: 10.1099/13500872-142-8-2207
– volume: 183
  start-page: 1527
  year: 1996
  ident: ppat.1008337.ref009
  article-title: Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall
  publication-title: J Exp Med
  doi: 10.1084/jem.183.4.1527
– volume: 189
  start-page: 730
  year: 2007
  ident: ppat.1008337.ref050
  article-title: Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon
  publication-title: J Bacteriol
  doi: 10.1128/JB.01190-06
– volume: 7
  start-page: 1702
  year: 2007
  ident: ppat.1008337.ref053
  article-title: Comprehensive analysis of exported proteins from Mycobacterium tuberculosis H37Rv
  publication-title: Proteomics
  doi: 10.1002/pmic.200600853
– volume: 8
  start-page: e78351
  year: 2013
  ident: ppat.1008337.ref018
  article-title: The ESX-3 secretion system is necessary for iron and zinc homeostasis in Mycobacterium tuberculosis
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0078351
– volume: 8
  start-page: e01720
  year: 2017
  ident: ppat.1008337.ref026
  article-title: PPE surface proteins are required for heme utilization by Mycobacterium tuberculosis
  publication-title: MBio
  doi: 10.1128/mBio.01720-16
– volume: 7
  start-page: e1002251
  year: 2011
  ident: ppat.1008337.ref039
  article-title: High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1002251
– volume: 105
  start-page: 3963
  year: 2008
  ident: ppat.1008337.ref028
  article-title: Disclosure of the mycobacterial outer membrane: cryo-electron tomography and vitreous sections reveal the lipid bilayer structure
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0709530105
– volume: 104
  start-page: 889
  year: 2017
  ident: ppat.1008337.ref048
  article-title: The diverse family of MmpL transporters in mycobacteria: from regulation to antimicrobial developments
  publication-title: Mol Microbiol
  doi: 10.1111/mmi.13675
– volume: 7
  start-page: 926
  year: 2015
  ident: ppat.1008337.ref005
  article-title: Metals in infectious diseases and nutritional immunity
  publication-title: Metallomics
  doi: 10.1039/C5MT90021B
– volume: 71
  start-page: 4159
  year: 2003
  ident: ppat.1008337.ref030
  article-title: Yersinia pestis TonB: role in iron, heme, and hemoprotein utilization
  publication-title: Infect Immun
  doi: 10.1128/IAI.71.7.4159-4162.2003
– volume: 92
  start-page: 5189
  year: 1995
  ident: ppat.1008337.ref008
  article-title: Iron acquisition by Mycobacterium tuberculosis: isolation and characterization of a family of iron-binding exochelins
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.92.11.5189
– volume: 34
  start-page: 99
  year: 1970
  ident: ppat.1008337.ref022
  article-title: Mycobactins: iron-chelating growth factors from mycobacteria
  publication-title: Bacteriol Rev
  doi: 10.1128/BR.34.2.99-125.1970
– volume: 48
  start-page: 77
  year: 2003
  ident: ppat.1008337.ref051
  article-title: Genes required for mycobacterial growth defined by high density mutagenesis
  publication-title: Mol Microbiol
  doi: 10.1046/j.1365-2958.2003.03425.x
– volume: 19
  start-page: 1639
  year: 2009
  ident: ppat.1008337.ref043
  article-title: Circos: an information aesthetic for comparative genomics
  publication-title: Genome Res
  doi: 10.1101/gr.092759.109
– volume: 91
  start-page: 1
  year: 2011
  ident: ppat.1008337.ref044
  article-title: TubercuList—10 years after
  publication-title: Tuberculosis (Edinb)
  doi: 10.1016/j.tube.2010.09.008
– volume: 9
  start-page: e102135
  year: 2014
  ident: ppat.1008337.ref056
  article-title: Acquired resistance of Mycobacterium tuberculosis to bedaquiline
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0102135
– volume: 190
  start-page: 3588
  year: 2008
  ident: ppat.1008337.ref066
  article-title: Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response
  publication-title: J Bacteriol
  doi: 10.1128/JB.01921-07
– volume: 111
  start-page: 1945
  year: 2014
  ident: ppat.1008337.ref013
  article-title: Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1311402111
– volume: 19
  start-page: 34
  year: 2014
  ident: ppat.1008337.ref058
  article-title: Heme uptake in bacterial pathogens
  publication-title: Curr Opin Chem Biol
  doi: 10.1016/j.cbpa.2013.12.014
– volume: 110
  start-page: 8206
  year: 2013
  ident: ppat.1008337.ref071
  article-title: Activation of heme biosynthesis by a small molecule that is toxic to fermenting Staphylococcus aureus
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1303674110
– volume: 5
  start-page: 1121
  year: 2013
  ident: ppat.1008337.ref054
  article-title: Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2013.10.031
– volume: 89
  start-page: 84
  year: 2009
  ident: ppat.1008337.ref057
  article-title: Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5 efflux system
  publication-title: Tuberculosis (Edinb)
  doi: 10.1016/j.tube.2008.08.003
– volume: 80
  start-page: 3650
  year: 2012
  ident: ppat.1008337.ref031
  article-title: A ferritin mutant of Mycobacterium tuberculosis is highly susceptible to killing by antibiotics and is unable to establish a chronic infection in mice
  publication-title: Infect Immun
  doi: 10.1128/IAI.00229-12
– volume: 5
  start-page: 631
  year: 1998
  ident: ppat.1008337.ref061
  article-title: Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin
  publication-title: Chem Biol
  doi: 10.1016/S1074-5521(98)90291-5
– volume: 1
  start-page: 149
  year: 2005
  ident: ppat.1008337.ref014
  article-title: Mycobactin-mediated iron acquisition within macrophages
  publication-title: Nat Chem Biol
  doi: 10.1038/nchembio717
– volume: 89
  start-page: 87
  year: 2011
  ident: ppat.1008337.ref029
  article-title: TonB or not TonB: is that the question?
  publication-title: Biochem Cell Biol
– volume: 191
  start-page: 95
  year: 1980
  ident: ppat.1008337.ref062
  article-title: Kinetics and mechanism of the interaction between human serum albumin and monomeric haemin
  publication-title: Biochem J
  doi: 10.1042/bj1910095
– volume: 288
  start-page: 24213
  year: 2013
  ident: ppat.1008337.ref060
  article-title: MmpL11 protein transports mycolic acid-containing lipids to the mycobacterial cell wall and contributes to biofilm formation in Mycobacterium smegmatis
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M113.473371
– volume: 1
  start-page: 109
  year: 2007
  ident: ppat.1008337.ref068
  article-title: A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2007.03.001
– volume: 26
  start-page: 601
  year: 2014
  ident: ppat.1008337.ref076
  article-title: The formation of the granuloma in tuberculosis infection
  publication-title: Semin Immunol
  doi: 10.1016/j.smim.2014.09.009
– volume: 1609
  start-page: 19
  year: 2003
  ident: ppat.1008337.ref049
  article-title: Beta-barrel membrane protein folding and structure viewed through the lens of alpha-hemolysin
  publication-title: Biochim Biophys Acta
  doi: 10.1016/S0005-2736(02)00663-6
– volume: 97
  start-page: 166
  year: 1965
  ident: ppat.1008337.ref020
  article-title: Isolation and structure of mycobactin T, a growth factor from Mycobacterium tuberculosis
  publication-title: Biochem J
  doi: 10.1042/bj0970166
– volume: 94
  start-page: 160
  year: 1965
  ident: ppat.1008337.ref021
  article-title: The structure of mycobactin p, a growth factor for Mycobacterium johnei, and the significance of its iron complex
  publication-title: Biochem J
  doi: 10.1042/bj0940160
– volume: 5
  start-page: 4730
  year: 2014
  ident: ppat.1008337.ref034
  article-title: Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin
  publication-title: Nat Commun
  doi: 10.1038/ncomms5730
– volume: 8
  start-page: e02133
  year: 2017
  ident: ppat.1008337.ref042
  article-title: Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis
  publication-title: MBio
  doi: 10.1128/mBio.02133-16
– volume: 91
  start-page: 98
  year: 2014
  ident: ppat.1008337.ref032
  article-title: IdeR is required for iron homeostasis and virulence in Mycobacterium tuberculosis
  publication-title: Mol Microbiol
  doi: 10.1111/mmi.12441
– volume: 7
  start-page: 245
  year: 2017
  ident: ppat.1008337.ref035
  article-title: Mycobacterium tuberculosis Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Functions as a Receptor for Human Lactoferrin
  publication-title: Front Cell Infect Microbiol
  doi: 10.3389/fcimb.2017.00245
– volume: 188
  start-page: 424
  year: 2006
  ident: ppat.1008337.ref010
  article-title: Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis
  publication-title: J Bacteriol
  doi: 10.1128/JB.188.2.424-430.2006
– volume: 3
  start-page: 80
  year: 2013
  ident: ppat.1008337.ref075
  article-title: Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans
  publication-title: Front Cell Infect Microbiol
  doi: 10.3389/fcimb.2013.00080
– volume: 78
  start-page: 4977
  year: 2010
  ident: ppat.1008337.ref070
  article-title: Overcoming the heme paradox: heme toxicity and tolerance in bacterial pathogens
  publication-title: Infect Immun
  doi: 10.1128/IAI.00613-10
– volume: 9
  start-page: 81
  year: 2019
  ident: ppat.1008337.ref074
  article-title: Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens
  publication-title: Front Cell Infect Microbiol
  doi: 10.3389/fcimb.2019.00081
– volume: 277
  start-page: 49727
  year: 2002
  ident: ppat.1008337.ref038
  article-title: Intraphagosomal Mycobacterium tuberculosis acquires iron from both extracellular transferrin and intracellular iron pools. Impact of interferon-gamma and hemochromatosis
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M209768200
– volume: 84
  start-page: 110
  year: 2004
  ident: ppat.1008337.ref006
  article-title: Iron, mycobacteria and tuberculosis
  publication-title: Tuberculosis
  doi: 10.1016/j.tube.2003.08.012
– volume: 184
  start-page: 1349
  year: 1996
  ident: ppat.1008337.ref037
  article-title: The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin
  publication-title: J Exp Med
  doi: 10.1084/jem.184.4.1349
– volume: 113
  start-page: E348
  year: 2016
  ident: ppat.1008337.ref019
  article-title: Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1523321113
– volume: 87
  start-page: e00540
  year: 2019
  ident: ppat.1008337.ref027
  article-title: PPE37 Is Essential for Mycobacterium tuberculosis Heme-Iron Acquisition (HIA), and a Defective PPE37 in Mycobacterium bovis BCG Prevents HIA
  publication-title: Infect Immun
  doi: 10.1128/IAI.00540-18
– volume: 111
  start-page: 6750
  year: 2014
  ident: ppat.1008337.ref081
  article-title: An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1400136111
– volume: 288
  start-page: 10101
  year: 2013
  ident: ppat.1008337.ref064
  article-title: A New Way to Degrade Heme: THE MYCOBACTERIUM TUBERCULOSIS ENZYME MhuD CATALYZES HEME DEGRADATION WITHOUT GENERATING CO
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M112.448399
– volume: 51
  start-page: 1518
  year: 2012
  ident: ppat.1008337.ref065
  article-title: Characterization of heme ligation properties of Rv0203, a secreted heme binding protein involved in Mycobacterium tuberculosis heme uptake
  publication-title: Biochemistry
  doi: 10.1021/bi2018305
– volume: 3
  start-page: 6
  year: 2003
  ident: ppat.1008337.ref063
  article-title: Crystal structural analysis of human serum albumin complexed with hemin and fatty acid
  publication-title: BMC Struct Biol
  doi: 10.1186/1472-6807-3-6
– volume: 192
  start-page: 861
  year: 2010
  ident: ppat.1008337.ref011
  article-title: The Mycobacterium tuberculosis high-affinity iron importer, IrtA, contains an FAD-binding domain
  publication-title: J Bacteriol
  doi: 10.1128/JB.00223-09
– volume: 73
  start-page: 3492
  year: 2005
  ident: ppat.1008337.ref047
  article-title: Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance
  publication-title: Infect Immun
  doi: 10.1128/IAI.73.6.3492-3501.2005
– volume: 240
  start-page: 252
  year: 2011
  ident: ppat.1008337.ref073
  article-title: Mycobacterium tuberculosis and the intimate discourse of a chronic infection
  publication-title: Immunol Rev
  doi: 10.1111/j.1600-065X.2010.00984.x
– volume: 14
  start-page: 99
  year: 2001
  ident: ppat.1008337.ref001
  article-title: Old iron, young copper: from Mars to Venus
  publication-title: Biometals
  doi: 10.1023/A:1016710810701
– volume: 14
  start-page: 320
  year: 2006
  ident: ppat.1008337.ref007
  article-title: Control of iron metabolism in Mycobacterium tuberculosis
  publication-title: Trends Microbiol
  doi: 10.1016/j.tim.2006.05.006
– volume: 200
  start-page: 1559
  year: 2004
  ident: ppat.1008337.ref052
  article-title: Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T cells
  publication-title: J Exp Med
  doi: 10.1084/jem.20041429
– volume: 9
  start-page: e1003120
  year: 2013
  ident: ppat.1008337.ref012
  article-title: Discovery of a siderophore export system essential for virulence of Mycobacterium tuberculosis
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1003120
– volume: 9
  start-page: 1483
  year: 2017
  ident: ppat.1008337.ref002
  article-title: The elemental role of iron in DNA synthesis and repair
  publication-title: Metallomics
  doi: 10.1039/C7MT00116A
– volume: 196
  start-page: 1250
  year: 2014
  ident: ppat.1008337.ref015
  article-title: Role for Mycobacterium tuberculosis membrane vesicles in iron acquisition
  publication-title: J Bacteriol
  doi: 10.1128/JB.01090-13
– volume: 193
  start-page: 1767
  year: 2011
  ident: ppat.1008337.ref023
  article-title: Mycobacterium tuberculosis can utilize heme as an iron source
  publication-title: J Bacteriol
  doi: 10.1128/JB.01312-10
– volume: 108
  start-page: 5051
  year: 2011
  ident: ppat.1008337.ref024
  article-title: Discovery and characterization of a unique mycobacterial heme acquisition system
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.1009516108
– volume: 3
  start-page: 55
  year: 2013
  ident: ppat.1008337.ref025
  article-title: Role and regulation of heme iron acquisition in gram-negative pathogens
  publication-title: Front Cell Infect Microbiol
– volume: 187
  start-page: 5658
  year: 2005
  ident: ppat.1008337.ref067
  article-title: Shigella dysenteriae ShuS promotes utilization of heme as an iron source and protects against heme toxicity
  publication-title: J Bacteriol
  doi: 10.1128/JB.187.16.5658-5664.2005
SSID ssj0041316
Score 2.5527802
Snippet Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e1008337
SubjectTerms Amide Synthases - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Transport
Biology and Life Sciences
Chromosomes
Efflux
Genetic research
Glycosylated hemoglobin
Heme
Heme - metabolism
Hemoglobin
Hemoglobins
Hemoglobins - metabolism
Humans
Infections
Iron
Iron - metabolism
Medicine and Health Sciences
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Mutants
Mutation
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - metabolism
Novels
Oxazoles - metabolism
Pathogenic microorganisms
Physiological aspects
Proteins
Research and Analysis Methods
Secretion
Siderophores
Siderophores - metabolism
Software
Transcription
Transcription (Genetics)
Transposon mutagenesis
Transposons
Tuberculosis
Utilization
Virulence
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3di9NAEF-kKPgifl_0lCiCT_HSbPbr8RSPE7SIX9zbsl_xCjUpTSP0v3cm2YZGTu7Ft5KdpN2Z2dmZdPb3I-SVtZXAQiOj1LCsDCpkyoJB5tRbpoI0tgcw_fFRLBby4kJ9PqD6wp6wAR54UNyJ4cYWc1MantPSVUJWniNR1sB9aB1GX8h69sXUEIMhMvekp0iKkwnKeTw0R8X8JNrozXptED4aUhDkQD_YlHrs_jFCz9arpr0q_fy7i_JgWzq7S-7EfDI9HeZxj9wI9X1ya2CY3D0g57jeN-FyaFNPTYQgSZsqxfNtKbjdKp7ETO0u_bRzsL57_ObuV7rtbNi4Dn7Zsn1Ivp-9__buPIvkCZmDLXebhVLNK1Y4zqq58wV8UqWTlZQWElXLrauUh-LKWcl8oLkTnnumcioLH5QtOX1EZnVThyOSMmm45aW3OYLlBau4EJBmeKirpQmMJYTutaddRBZHgouV7v8uE1BhDMrQqHMddZ6QbLxrPSBrXCP_Fg0zyiIudn8BvEVHb9HXeUtCXqJZNSJf1Nha89N0bas_fF3oU8jtEE4rp_8U-jIReh2FqgYm60w8zgAqQ0StieTxRBLWr5sMH6GL7efc6oIK0C-D6At37t3u6uEX4zA-FNvl6tB0KANVoFQQARPyePDSUW-0yDm-xUqImPjvRLHTkXp52QOPw9dKWtIn_8MST8ntAl9dILeOPCaz7aYLz8hN93u7bDfP-9X8B6cRTZU
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Public Library of Science (PLoS) Journals Open Access
  dbid: FPL
  link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1Lj9MwELaggMSFN2xgQQEhcQqbxPHruCCqRVqqFS_tzbIdh61UkqppkPrvmUncQlZbIW5VPE7jz-PxTDL-hpDX1lYCA42EUsOSwiufKAsTktHSMuWlsT2B6fdTMZvJ83N19idQvPQFn4rsKGD6drk0SPcMLgMV18mNnHKOKVzTs9Ot5QV7nPFwPG5fz9H207P072zxZLlo2qsczcv5kn9tQNO7__vo98id4GrGx4Nu3CfXfP2A3BqKT24ekhM0BSt_MWSwxyawk8RNFePRtxg0chEOacZ2E3_aOFj6PbVz9zNed9avXAdDmbePyLfph6_vT5JQVyFxsBuvE1-orGK546zKXJnDL1U4WUlpwYe13LpKlRB3OStZ6WnqRMlLplIq89IrW3D6mEzqpvYHJGbScMuL0qbIo-et4kKAB1JCyC2NZywidAu3doF0HGtfLHT_JU1A8DGAoREjHTCKSLLrtRxIN_4h_w5ncieLlNn9BZgMHVagNtzYPDOF4SktXCVkVXKsuDYU0bQuIq9QDzSSYtSYdfPDdG2rP36Z6WNw-5BpK6V7hT6PhN4EoaqBwToTTjoAZEi2NZI8HEnC0naj5gPUye2YW51TAfgyMMzQc6unVze_3DXjTTGTrvZNhzIQIEoFxjEiTwa13uFG85TjC66IiJHCj4Adt9Tzi56THP5W0oI-3f_Ez8jtHN9VYDEdeUgm61Xnn5Ob7td63q5e9Av5NwroSGw
  priority: 102
  providerName: Public Library of Science
Title Comprehensive analysis of iron utilization by Mycobacterium tuberculosis
URI https://www.ncbi.nlm.nih.gov/pubmed/32069330
https://www.proquest.com/docview/2377705030
https://www.proquest.com/docview/2358589200
https://pubmed.ncbi.nlm.nih.gov/PMC7058343
https://doaj.org/article/a6ab21a4a6034cf78fd67238004698bc
http://dx.doi.org/10.1371/journal.ppat.1008337
Volume 16
WOSCitedRecordID wos000518637800007&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVAON
  databaseName: DOAJ Directory of Open Access Journals
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: DOA
  dateStart: 20050101
  isFulltext: true
  titleUrlDefault: https://www.doaj.org/
  providerName: Directory of Open Access Journals
– providerCode: PRVPQU
  databaseName: Biological Science Database
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: M7P
  dateStart: 20050901
  isFulltext: true
  titleUrlDefault: http://search.proquest.com/biologicalscijournals
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Health & Medical Collection
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: 7X7
  dateStart: 20050901
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/healthcomplete
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: BENPR
  dateStart: 20050901
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Publicly Available Content
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: PIMPY
  dateStart: 20050901
  isFulltext: true
  titleUrlDefault: http://search.proquest.com/publiccontent
  providerName: ProQuest
– providerCode: PRVATS
  databaseName: Public Library of Science (PLoS) Journals Open Access
  customDbUrl:
  eissn: 1553-7374
  dateEnd: 99991231
  omitProxy: false
  ssIdentifier: ssj0041316
  issn: 1553-7374
  databaseCode: FPL
  dateStart: 20050101
  isFulltext: true
  titleUrlDefault: http://www.plos.org/publications/
  providerName: Public Library of Science
link http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1Lb9NAEF7RFCQuvKGBEhmExMnU9tr7OKEWNWqlNrLKQ-Fk7cttpGCHOEbKv2dnvQk1KnDgYkXesZ3dHc_OjGe_D6E3UpYUAo0QY5GFqeEm5NJOSIy1zLhhQjoA0y9ndDJh0ynPfcKt8WWVG5voDLWuFeTIDxJMKQXwkuj94nsIrFHwddVTaOygXUBJwK50L99YYmufHfUpUOOEFBPit85hGh_4mXq3WAgAkbaOCDChX1uaHIL_1k4PFvO6uckJ_b2W8triNL7_v916gO55tzQ47PToIbplqkfoTkdUuX6MTsBsLM1VV-0eCI9kEtRlANvkAqu9c7-hM5Dr4HytrJlwMNDtt2DVSrNUre3arHmCPo-PP304CT0HQ6jsyr0KTcrjMksUycpY6cT-4qliJWPS-ruSSFVybWM0JVmmDY4U1URnPMIs0YbLlOCnaFDVldlDQcYEkSTVMgLMPSM5sT3nsbbhORMmy4YIb4a_UB6gHHgy5oX76kZtoNINRgGTVvhJG6Jwe9WiA-j4h_wRzOxWFuC13Yl6eVn4t7UQRMgkFqkgEU5VSVmpCbCzdYSbUg3Ra9CLAgA0KqjQuRRt0xSnHyfFoXURAZUrwn8UuugJvfVCZW07q4TfFWGHDIC5epL7PUlrBlSveQ90dNPnpvilWfbKje7d3Pxq2ww3haq7ytQtyNhgknFrSIfoWafm23HDSUQgGTZEtPcC9Aa231LNrhx-uX0swyl-_ve_9QLdTSC3AeQ7bB8NVsvWvES31Y_VrFmO0A6dUndkI7R7dDzJL0Yun2KP4_xs5AyBbclPz_OvPwGasWL9
linkProvider ProQuest
linkToHtml http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1bb9MwFLZGAY0X7myFAQGBeApL4sSxHxAal6nVumqCDe0t2I6zVSpJaRpQ_xS_kXMSpyxowNMeeKvqk7Q-OTc7x99HyDOlshgXGi6lMnJDI4wrFDwQn6YqEoZLVQOYfhrF4zE_PhYHa-RHexYG2yrbmFgH6rTQuEe-HdA4jhG8xHs9--oiaxS-XW0pNBqz2DPL77BkK18N38HzfR4Eu-8P3w5cyyrgashFC9eEws-iQLMo83UawCcRap5xrqCCU0zpTKSw6tCKR6mhno5TlkbCozxIjVAho3DfS-QylBEBr1sFD9rID_mgplpFKh43pozZo3o09retZbyczSSCVkPhg8zrZ1JhzRiwygu92bQozyt6f-_dPJMMd2_8b2q8Sa7bstvZafzkFlkz-W1ytSHiXN4hAwyLc3PadPM70iK1OEXm4DFAB7xzag-sOmrp7C81hMEa5rr64iwqZea6AlVOyrvk6EKmcY_08iI3m8SJuGSKhanyEFPQKMFA08JPBVRh0kRRn9D2cSfaArAjD8g0qd8qxrAQa5SRoJEk1kj6xF1dNWsASP4h_wYtaSWL8OH1F8X8JLHRKJFMqsCXoWQeDXUW8yxlyD7XEIoq3SdP0Q4TBAjJsQPpRFZlmQw_jpMdKIERdcyjfxT60BF6YYWyAiarpT31ASpD4LGO5FZHEsKc7gxvok-0cy6TX5YMV7a2fv7wk9Uw3hS7CnNTVCgDi2UuIFH0yUbjViu90cBjuNnXJ3HH4TqK7Y7kk9Manx1-ltOQ3v_733pM1geH-6NkNBzvPSDXAtzHQaIhvkV6i3llHpIr-ttiUs4f1UHGIZ8v2h1_AlI3ueM
linkToPdf http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9NAEF6V8BAX3tBAAYNAnExsr72PA0KFUjVqiSJe6s3srtdtpBCHOAblr_HrmLHXoUYFTj1wi7JjJzue165nv4-QJ1rnHBcaPqUq8WMrrS81PJCQZjqRVihdA5h-OuCjkTg8lOMN8qM9C4NtlW1MrAN1VhjcIx9ElHOO4CXBIHdtEeOd3Zfzrz4ySOGb1pZOozGRfbv6Dsu38sVwB5710yjaffPh9Z7vGAZ8A3lp6dtYhnkSGZbkocki-CRjI3IhNFRzmmmTywxWIEaLJLM0MDxjWSIDKqLMSh0zCvc9R85zBC2v2wbHbRaA3FDTriItj88pY-7YHuXhwFnJ8_lcIYA1FEHIwn4iLdbsAesc0ZtPi_K0Avj3Ps4TiXH36v-s0mvkiivHve3Gf66TDTu7QS42BJ2rm2QPw-XCHjdd_p5yCC5ekXt4PNADr526g6yeXnlvVwbCYw1_XX3xlpW2C1OBWiflLfLxTKZxm_RmxcxuEi8RimkWZzpArEGrJQOtyzCTUJ0pmyR9QttHnxoHzI78INO0ftvIYYHWKCNFg0mdwfSJv75q3gCT_EP-FVrVWhZhxesvisVR6qJUqpjSUahixQIam5yLPGPIStcQjWrTJ4_RJlMEDpmhvRypqizT4ftRug2lMaKRBfSPQu86Qs-cUF7AZI1yp0FAZQhI1pHc6khC-DOd4U30j3bOZfrLquHK1u5PH360HsabYrfhzBYVysAiWkhIIH1yp3Gxtd5oFDDcBOwT3nG-jmK7I7PJcY3bDj8raEzv_v1vPSSXwAvTg-Fo_x65HOH2DvIPiS3SWy4qe59cMN-Wk3LxoI43Hvl81t74E65IwqA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Comprehensive+analysis+of+iron+utilization+by+Mycobacterium+tuberculosis&rft.jtitle=PLoS+pathogens&rft.au=Zhang%2C+Lei&rft.au=R+Curtis+Hendrickson&rft.au=Meikle%2C+Virginia&rft.au=Lefkowitz%2C+Elliot+J&rft.date=2020-02-18&rft.pub=Public+Library+of+Science&rft.issn=1553-7366&rft.eissn=1553-7374&rft.volume=16&rft.issue=2&rft.spage=e1008337&rft_id=info:doi/10.1371%2Fjournal.ppat.1008337&rft.externalDBID=HAS_PDF_LINK
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7374&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7374&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7374&client=summon