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Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and Improperly Depositing MAC

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Titel: Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and Improperly Depositing MAC
Autoren: Michal Magda, Wendy Boschloo, Serena Bettoni, Derek Fairley, Thomas A. Russo, Christian G. Giske, Chaitanya Tellapragada, Suzan H.M. Rooijakkers, Kristian Riesbeck, Anna M. Blom
Weitere Verfasser: MMB-imm, Infection & Immunity
Quelle: J Innate Immun
Journal of Innate Immunity, Vol 17, Iss 1, Pp 112-125 (2025)
Verlagsinformationen: S. Karger AG, 2025.
Publikationsjahr: 2025
Schlagwörter: Acinetobacter baumannii, Virulence, Virulence Factors, Complement Membrane Attack Complex/metabolism, Virulence Factors/metabolism, Complement Membrane Attack Complex, Complement System Proteins, Moths, RC31-1245, Immunity, Innate, Acinetobacter Infections/immunology, Moths/microbiology, Acinetobacter baumannii/immunology, Journal Article, Medicine, Animals, Humans, Complement System Proteins/metabolism, Internal medicine, Complement Activation, Research Article, Acinetobacter Infections, Immune Evasion
Beschreibung: Introduction: Acinetobacter baumannii is a gram-negative opportunistic bacterium that causes life-threatening infections in immunocompromised hosts. The complement system is a critical mechanism of innate immunity that protects the human body from bacterial infections. Complement activation leads to the deposition of the membrane attack complex (MAC), which can directly lyse gram-negative bacteria. However, A. baumannii has developed evasion mechanisms to protect itself from complement. Methods: Complement deposition was investigated by flow cytometry and Western blotting. Soluble MAC formation was assessed by ELISA. Bacterial serum resistance was determined by the SYTOX Green Assay. Galleria mellonella was used as an infection model. Genome sequencing revealed virulence genes carried by isolates. Results: We examined clinical isolates of A. baumannii and found 11 isolates with MAC deposition and 5 isolates without deposition. Trypsinization of MAC-positive isolates significantly reduced MAC, indicating incorrect insertion, consistent with a lack of lysis of these strains. MAC-negative isolates inhibited alternative pathway activation and were significantly more serum-resistant. These strains were also more virulent in a G. mellonella infection model. Whole genome sequencing revealed that MAC-negative isolates carried more virulence genes, and both MAC-negative and MAC-positive A. baumannii significantly differed in capsule type. Importantly, a correlation was observed between complement inhibition and capsule type (e.g., capsule locus KL171) of MAC-negative bacteria, while the capsule type (e.g., KL230) of MAC-positive A. baumannii was associated with increased sensitivity to MAC-mediated lysis. Conclusion: Our findings suggest a relationship between capsule type, complement resistance, and host virulence in A. baumannii.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1662-8128
1662-811X
DOI: 10.1159/000543664
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/39842423
https://doaj.org/article/cec289e1743e4a4baac7a73a9cc29005
https://dspace.library.uu.nl/handle/1874/460737
Rights: CC BY
URL: http://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) (http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.
Dokumentencode: edsair.doi.dedup.....8f3ba5ac64cbc69edfd0049103a5e3fd
Datenbank: OpenAIRE
Beschreibung
Abstract:Introduction: Acinetobacter baumannii is a gram-negative opportunistic bacterium that causes life-threatening infections in immunocompromised hosts. The complement system is a critical mechanism of innate immunity that protects the human body from bacterial infections. Complement activation leads to the deposition of the membrane attack complex (MAC), which can directly lyse gram-negative bacteria. However, A. baumannii has developed evasion mechanisms to protect itself from complement. Methods: Complement deposition was investigated by flow cytometry and Western blotting. Soluble MAC formation was assessed by ELISA. Bacterial serum resistance was determined by the SYTOX Green Assay. Galleria mellonella was used as an infection model. Genome sequencing revealed virulence genes carried by isolates. Results: We examined clinical isolates of A. baumannii and found 11 isolates with MAC deposition and 5 isolates without deposition. Trypsinization of MAC-positive isolates significantly reduced MAC, indicating incorrect insertion, consistent with a lack of lysis of these strains. MAC-negative isolates inhibited alternative pathway activation and were significantly more serum-resistant. These strains were also more virulent in a G. mellonella infection model. Whole genome sequencing revealed that MAC-negative isolates carried more virulence genes, and both MAC-negative and MAC-positive A. baumannii significantly differed in capsule type. Importantly, a correlation was observed between complement inhibition and capsule type (e.g., capsule locus KL171) of MAC-negative bacteria, while the capsule type (e.g., KL230) of MAC-positive A. baumannii was associated with increased sensitivity to MAC-mediated lysis. Conclusion: Our findings suggest a relationship between capsule type, complement resistance, and host virulence in A. baumannii.
ISSN:16628128
1662811X
DOI:10.1159/000543664