CONICET | Buscador de Institutos y Recursos Humanos

Infections due to multi-drug resistant Acinetobacter baumannii are associated with high morbidity and mortality among critically-ill and immunocompromised patients. Novel approaches to prevent and treat these infections are needed, and inhibitors blocking virulence factors are promising alternatives to antimicrobials for the treatment of pan-drug resistant strains [1, 2]. Outer membrane (OM) proteins functioning at the interface with the environment constitute prime candidates for the design of inhibitors aimed to disturb recognition of target cells by the pathogen [1, 2]. Here, we evaluated the potential roles of CarO, an OM protein found only among Moraxellaceae family members [3], in A. baumannii virulence.Wild-type A. baumannii strain ATCC 17978 (WT), its isogenic carO deletion mutant (carO), and the carO strain complemented with plasmid pWH1266-carO expressing CarO were used. Using an experimental murine model of peritoneal sepsis and C57BL/6 female mice, the minimum lethal dose for the WT strain and the carO mutant were 3.20 log10 CFU/mL and 4.32 log10 CFU/mL, respectively. Using an inoculum of 3.2 log10 CFU/mL, all mice infected with the WT strain died within 24 h, 67% of mice infected with the carO mutant within 48 h, and all mice infected with the complemented strain within 24-48 h. Mice infected with the carO mutant showed significantly less bacterial burden at 8 h and 24 h-post infection in spleen, lung, kidney, liver, peritoneal fluid, and blood when compared with animals infected with the WT strain or the complemented carO strain. The overall results indicate that the loss of CarO significantly reduces, but not abolishes, the pathogenicity of the ATCC17978 strain in a murine model, pointing to this OM protein as part of the A. baumannii virulence repertoire and potential target for drug design.