The respiratory chain of Klebsiella aerogenes in urine-like conditions: critical roles of NDH-2 and bd-terminal oxidases

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Název: The respiratory chain of Klebsiella aerogenes in urine-like conditions: critical roles of NDH-2 and bd-terminal oxidases
Autoři: Martín A. González-Montalvo, Jennifer M. Sorescu, Gabriella Baltes, Oscar Juárez, Karina Tuz
Zdroj: Front Microbiol
Frontiers in Microbiology, Vol 15 (2024)
Informace o vydavateli: Frontiers Media SA, 2024.
Rok vydání: 2024
Témata: 0301 basic medicine, 0303 health sciences, 03 medical and health sciences, Klebsiella aerogenes, NDH-2, oxidase, Enterobacter aerogenes, Microbiology, bacteria metabolism, QR1-502, bd-terminal oxidase
Popis: Klebsiella aerogenes is an opportunistic nosocomial bacterial pathogen that commonly causes urinary tract infections. Over the past decades, K. aerogenes strains have acquired resistance to common antibiotics that has led to the rise of multidrug-resistant and even pandrug-resistant strains. Infections produced by these strains are nearly impossible to treat, which makes K. aerogenes a global priority to develop new antibiotics and there is an urgent need to identify targets to treat infections against this pathogen. However, very little is known about the metabolism and metabolic adaptations of this bacterium in infection sites. In this work, we investigated the respiratory metabolism of K. aerogenes in conditions that resemble human urine, allowing us to identify novel targets for antibiotic development. Here we describe that, unlike other gram-negative pathogens, K. aerogenes utilizes the type-2 NADH dehydrogenase (NDH-2) as the main entry point for electrons in the respiratory chain in all growth conditions evaluated. Additionally, in urine-like media, the aerobic metabolism as a whole is upregulated, with significant increases in succinate and lactate dehydrogenase activity. Moreover, our data show that the bd-I type oxidoreductases are the main terminal oxidases of this microorganism. Our findings support an initial identification of NDH-2 and bd-I oxidase as attractive targets for the development of new drugs against K. aerogenes as they are not found in human hosts.
Druh dokumentu: Article
Other literature type
ISSN: 1664-302X
DOI: 10.3389/fmicb.2024.1479714
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/39568993
https://doaj.org/article/bf19a5168b3f4135b6e6b491a0e24b45
Rights: CC BY
Přístupové číslo: edsair.doi.dedup.....d1c1db0f8e7ae70273a1358c71527cf4
Databáze: OpenAIRE
Popis
Abstrakt:Klebsiella aerogenes is an opportunistic nosocomial bacterial pathogen that commonly causes urinary tract infections. Over the past decades, K. aerogenes strains have acquired resistance to common antibiotics that has led to the rise of multidrug-resistant and even pandrug-resistant strains. Infections produced by these strains are nearly impossible to treat, which makes K. aerogenes a global priority to develop new antibiotics and there is an urgent need to identify targets to treat infections against this pathogen. However, very little is known about the metabolism and metabolic adaptations of this bacterium in infection sites. In this work, we investigated the respiratory metabolism of K. aerogenes in conditions that resemble human urine, allowing us to identify novel targets for antibiotic development. Here we describe that, unlike other gram-negative pathogens, K. aerogenes utilizes the type-2 NADH dehydrogenase (NDH-2) as the main entry point for electrons in the respiratory chain in all growth conditions evaluated. Additionally, in urine-like media, the aerobic metabolism as a whole is upregulated, with significant increases in succinate and lactate dehydrogenase activity. Moreover, our data show that the bd-I type oxidoreductases are the main terminal oxidases of this microorganism. Our findings support an initial identification of NDH-2 and bd-I oxidase as attractive targets for the development of new drugs against K. aerogenes as they are not found in human hosts.
ISSN:1664302X
DOI:10.3389/fmicb.2024.1479714