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

Magda, Michal LU orcid ; Boschloo, Wendy LU ; Bettoni, Serena LU orcid ; Fairley, Derek ; Russo, Thomas A. ; Giske, Christian G. ; Tellapragada, Chaitanya ; Rooijakkers, Suzan H.M. LU ; Riesbeck, Kristian LU orcid and Blom, Anna M. LU orcid (2025) In Journal of Innate Immunity p.112-125
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 gramnegative bacteria. However, A. baumannii has developed evasion mechanisms to protect itself from complement. Methods: Complement deposition was investigated by flow cytometry and Western blotting. SolubleMAC formation was assessed by ELISA. Bacterial serum resistance was determined by the SYTOX Green Assay. Galleria mellonella was used as an infection model.... (More)

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 gramnegative bacteria. However, A. baumannii has developed evasion mechanisms to protect itself from complement. Methods: Complement deposition was investigated by flow cytometry and Western blotting. SolubleMAC 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 serumresistant. 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 MACnegative 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.

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organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Acinetobacter baumannii, Complement system, Evasion mechanism, Galleria mellonella, Membrane attack complex
in
Journal of Innate Immunity
pages
14 pages
publisher
Karger
external identifiers
  • pmid:39842423
  • scopus:85219757222
ISSN
1662-811X
DOI
10.1159/000543664
language
English
LU publication?
yes
id
9dc092cd-6c0d-4ca6-a30f-a49d34e16f95
date added to LUP
2025-06-30 09:21:34
date last changed
2025-07-14 09:56:55
@article{9dc092cd-6c0d-4ca6-a30f-a49d34e16f95,
  abstract     = {{<p>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 gramnegative bacteria. However, A. baumannii has developed evasion mechanisms to protect itself from complement. Methods: Complement deposition was investigated by flow cytometry and Western blotting. SolubleMAC 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 serumresistant. 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 MACnegative 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.</p>}},
  author       = {{Magda, Michal and Boschloo, Wendy and Bettoni, Serena and Fairley, Derek and Russo, Thomas A. and Giske, Christian G. and Tellapragada, Chaitanya and Rooijakkers, Suzan H.M. and Riesbeck, Kristian and Blom, Anna M.}},
  issn         = {{1662-811X}},
  keywords     = {{Acinetobacter baumannii; Complement system; Evasion mechanism; Galleria mellonella; Membrane attack complex}},
  language     = {{eng}},
  pages        = {{112--125}},
  publisher    = {{Karger}},
  series       = {{Journal of Innate Immunity}},
  title        = {{Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and Improperly Depositing MAC}},
  url          = {{http://dx.doi.org/10.1159/000543664}},
  doi          = {{10.1159/000543664}},
  year         = {{2025}},
}