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Acinetobacter baumannii Clinical Isolates Resist Complement-Mediated Lysis by Inhibiting the Complement Cascade and
Michal Magda1, Wendy Boschloo1, Serena Bettoni1
1Department of Translational Medicine, Lund University, Malmö, Sweden.
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.
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.
Insights
Acinetobacter baumannii strains with specific capsule types evade the human complement system, leading to increased serum resistance and virulence. Understanding this relationship is key to combating these dangerous infections.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Acinetobacter baumannii is a dangerous opportunistic pathogen.
- The human complement system, including the membrane attack complex (MAC), defends against bacterial infections.
- A. baumannii employs evasion strategies against complement-mediated lysis.
Purpose of the Study:
- To investigate the mechanisms by which A. baumannii evades complement.
- To determine the role of capsule type in complement resistance and virulence.
Main Methods:
- Flow cytometry and Western blotting for complement deposition.
- ELISA for soluble MAC formation.
- SYTOX Green Assay for serum resistance.
- Galleria mellonella infection model.
- Whole genome sequencing.
Main Results:
- 11 of 16 clinical isolates showed MAC deposition; 5 did not.
- MAC-negative isolates exhibited increased serum resistance and virulence.
- MAC-negative isolates inhibited alternative pathway activation.
- Genome sequencing revealed more virulence genes in MAC-negative strains.
- Distinct capsule types were associated with MAC deposition or inhibition (e.g., KL171 vs. KL230).
Conclusions:
- Capsule type is linked to complement resistance in A. baumannii.
- A. baumannii capsule type influences virulence and evasion of innate immunity.
- Findings highlight the interplay between bacterial genetics, immune evasion, and pathogenesis.
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