IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The Acinetobacter baumannii outer membrane protein CarO exhibits virulence factor roles in a murine infection model
Autor/es:
CEBRERO-CANGUIRO T; VIALE AM; SMANI Y; MORAN BARRIO J; LABRADOR-HERRERA G; PACHÓN J; PACHÓN-IBAÑEZ ME
Lugar:
Frankfurt
Reunión:
Simposio; Acinetobacter 2019 - 12th International Symposium on the Biology of Acinetobacter; 2019
Institución organizadora:
Institute of Molecular Biosciences Goethe-University Frankfurt
Resumen:
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.