UC San Diego

Acinetobacter baumannii is an emerging gram-negative pathogen that is listed by the center of disease control as an urgent threat and is part of a select group of pathogens known as the ESKAPE pathogens due to its ability to continuously escape the lethal action of antibiotics. A. baumannii infection is most common in the healthcare setting putting immunocompromised patients at increased risk of infection through disease such as ventilator associated pneumonia. For pathogens such as A. baumannii, the mechanisms of antimicrobial resistance are well understood but the understanding of the determinants of virulence have yet to catch up. A virulence factor of particular interest in the scientific community is the capsular polysaccharide and how it can play a role in pathogenicity. Bacterial capsules, comprised of tightly packed polysaccharide units, have been shown to provide various strains of bacteria protection from environmental pressures such as host immune response and antimicrobial agents. However, capsule loci in A. baumannii are highly variable providing the question if capsular virulence is specific to certain capsule types or universal. This study generated an unmarked knockout mutant of LAC-4 in which the capsule locus has been deleted. The resulting mutant was evaluated with in vitro cell based assays and against an established mouse model of bacterial systemic infection. Capsule deficient mutants of LAC-4 were found to be significantly less virulent than the wildtype LAC-4 strain showing that the capsule gene cluster appears to contribute to LAC-4’s hypervirulence.