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Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Acinetobacter baumannii Clinical
Elisabet Bjånes1, Truman Koh1, Tariq Qayum1
1Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
Abstract:
The frequently multidrug-resistant bacterial pathogen Acinetobacter baumannii is a leading cause of nosocomial infections, including ventilator-associated pneumonia, such that the World Health Organization and US Centers for Disease Control and Prevention have declared it a top priority candidate for novel drug development. Nearly all clinical A. baumannii strains express a thick surface polysaccharide capsule that protects against desiccation, host defenses, and disinfectants. In this study, we investigated the contribution of the polysaccharide capsule to virulence caused by the A. baumannii clinical isolate Ab Lac-4, which is rare in its ability to cause pneumonia and disseminated sepsis in healthy mice. We assessed the role of the capsule in wildtype Lac-4 (WT) by generating a premature stop codon in wza, which codes for the polysaccharide export protein. The wza# mutant was hypersensitive to killing by complement, whole blood, and healthy human neutrophils compared to WT and a revertant mutant (wza-Rev). Furthermore, the wza# mutant was highly attenuated in murine sepsis and unable to disseminate from the lungs during pneumonia. This study reinforces the capsule as a key contributor to Ab Lac-4 hypervirulence.
Insights
The bacterial pathogen Acinetobacter baumannii
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Acinetobacter baumannii is a multidrug-resistant pathogen causing hospital-acquired infections.
- Its polysaccharide capsule aids survival against host defenses and disinfectants.
- The WHO and CDC identify it as a priority for new drug development.
Purpose of the Study:
- To investigate the role of the polysaccharide capsule in the virulence of Acinetobacter baumannii clinical isolate Ab Lac-4.
- To determine the capsule's contribution to pneumonia and sepsis in a murine model.
Main Methods:
- Generated a mutant (wza#) with a premature stop codon in the wza gene, which encodes a polysaccharide export protein.
- Assessed the mutant's susceptibility to complement, whole blood, and neutrophils.
- Evaluated the mutant's virulence in murine sepsis and pneumonia models.
Main Results:
- The wza# mutant showed increased susceptibility to killing by complement, whole blood, and neutrophils compared to wildtype.
- The wza# mutant was significantly attenuated in murine sepsis.
- The wza# mutant failed to disseminate from the lungs during pneumonia.
Conclusions:
- The polysaccharide capsule is crucial for the hypervirulence of Acinetobacter baumannii Ab Lac-4.
- Capsule production is essential for evading host immune responses and establishing infection.
- Targeting capsule synthesis could be a promising strategy for novel antimicrobial therapies.
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