Exploring Roles of the Polysaccharide Capsule in Pathogenesis of Hypervirulent Acinetobacter baumannii Clinical Isolate Lac-4

The frequently multidrug-resistant bacterial pathogen 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...

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Bibliographic Details
Published in:Antibiotics (Basel) 2024-01, Vol.13 (1), p.10
Main Authors: Bjånes, Elisabet, Koh, Truman, Qayum, Tariq, Zurich, Raymond, McCabe, Sinead, Hampel, Kegan, Cartwright, Lisa, Nizet, Victor
Format: Article
Language:English
Subjects:
Acinetobacter baumannii
antibiotic resistance
Antibiotics
Antimicrobial agents
bacterial infections
Desiccation
Disease control
Disinfectants
Drug development
Genes
Genomes
Immune system
Infections
Leukocytes (neutrophilic)
Lungs
Multidrug resistance
Mutants
Neutrophils
Nonsense mutation
Nosocomial infection
Pathogenesis
Pathogens
Pneumonia
polysaccharide capsule
Polysaccharides
Protein transport
Sepsis
Stop codon
Ventilator-associated pneumonia
Virulence
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Summary:The frequently multidrug-resistant bacterial pathogen 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 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 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 , which codes for the polysaccharide export protein. The mutant was hypersensitive to killing by complement, whole blood, and healthy human neutrophils compared to WT and a revertant mutant ( ). Furthermore, the 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.
ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics13010010