Abstract
ABSTRACT Novel approaches to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections are urgently needed and anti-virulence drugs represent promising alternatives, but our knowledge on potential targets is scarce. We searched for potential A. baumannii 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 carO 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 A. baumannii CarO was analyzed in model systems, isogenic ΔcarO mutants and a CRAB clinical isolate with truncated CarO, showed lower ability to adhere and invade A549 cells and in vivo virulence. This unnoticed virulence role for CarO postulate this A. baumannii outer membrane protein as a potential target for new therapies against CRAB infections.
Highlights
Acinetobacter baumannii is one of the most successful opportunistic pathogens responsible for healthcareacquired infections worldwide [1]
We first investigated the virulence fac tors of carbapenem-resistant A. baumannii (CRAB) clinical isolates from six adult patients with bloodstream infections (BSI) secondary to A. baumannii ventilated associated pneumonia (VAP). Despite their demographics and clinical characteristics homo geneity, as well as receiving optimal therapy with colistin, three patients survived while the others three did not, despite not having antecedents of other acute and severe infections, or chronic underlying diseases
Additional genetic evidence indicating a virulence role in A. baumannii for CarO was obtained by using the model type strains ATCC 17978 and ATCC 19606, their isogenic ΔcarO mutants, and the ΔcarO mutants complemented with a plasmid reinstating CarO expression, as well as two of the CRAB clinical isolates
Summary
Acinetobacter baumannii is one of the most successful opportunistic pathogens responsible for healthcareacquired infections worldwide [1]. Crude mortality rates in these patients have been reported between 30% and 76% [3]. This pathogen is endowed with an extraordinary capability to develop resistance to anti biotics, including carbapenems [1,2,3]. This situation has prompted the search of new therapeutic strategies to deal with carbapenem-resistant A. baumannii (CRAB) infec tions, and non-antimicrobial approaches targeting bacter ial virulence factors might represent promising alternatives [4]. The origin of the strains and the patients’ clinical characteristics should be carefully con sidered when drawing conclusions on possible virulence factors, or these might not be definite [7,8,9]
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