Virulence role of the outer membrane protein CarO in carbapenem-resistant <i>Acinetobacter baumannii</i>

Abstract

Novel approaches to treat carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) infections are urgently needed and anti-virulence drugs represent promising alternatives, but our knowledge on potential targets is scarce. We searched for potential <i>A. baumannii</i> virulence factors by whole-genome sequencing-based comparisons of CRAB clinical isolates causing bloodstream infections secondary to ventilator-associated pneumonia from demographics and clinically homogeneous patients, who received optimal treatment but with different clinical outcomes. Thus, the <i>carO</i> gene was interrupted in CRAB isolates from surviving patients, while it was intact in isolates from non-surviving patients, and proteomic/immunoblot techniques corroborated it. When the virulence role of <i>A. baumannii</i> CarO was analyzed in model systems, isogenic Δ<i>carO</i> mutants and a CRAB clinical isolate with truncated CarO, showed lower ability to adhere and invade A549 cells and <i>in vivo</i> virulence. This unnoticed virulence role for CarO postulate this <i>A. baumannii</i> outer membrane protein as a potential target for new therapies against CRAB infections.