Author(s): Rafael López-Rojas 1 , Younes Smani 2 , Jerónimo Pachón 3 *
Acinetobacter baumannii; antimicrobial resistance; therapeutic alternatives; virulence factors
Acinetobacter baumannii is one of the most prevalent causes of severe hospital-acquired infections, such as ventilator-associated pneumonia, bacteremia and meningitis, among others, with a high rate of morbidity and mortality  . This microorganism has turned, in recent years, from an opportunistic bacterium, even with controversial pathogenicity  , to be included in the top-seven list of 'bad bugs' with a lack of appropriate treatment by the Infectious Diseases Society of America  . Besides other characteristics, such as its ability to survive on dry surfaces for 5 months and its high tolerance to wide ranges of pH, temperatures and humidity, it is its array of intrinsic and acquired antibiotic-resistance genes that has prompted A. baumannii to be a major cause of concern, changing from being susceptible to almost all antimicrobials in the early 1970s to the accumulation of numerous outbreaks of resistant strains to all commercially available antibiotics nowadays  . In this article, we try to review the main works of a new approach to circumvent the lack of treatment against A. baumannii by blocking its virulence factors.
Virulence mechanisms in A. baumannii
Recent whole-genome sequencing studies involving A. baumannii have demonstrated not only a vast array of antibiotic drug resistance determinants but also many pathogenicity islands  . Studies of specific virulence mechanisms have recently been reviewed  , focusing on biofilm formation - more related to the ability to persist on surfaces and host rather than on infectiveness; siderophore-mediated iron acquisition systems, including acinetobactin, which allows A. baumannii to acquire ferric ions under the iron-limited host conditions - bacterial quorum sensing used to assess their local population densities through molecule signals; adherence to, and invasion of host cells, to escape the host immune system and to cross the epithelia of tissues to increase its replication; cytotoxicity dependent on outer membrane proteins and outer membrane vesicles that are involved in the first contact with the host; phospholipase D, which plays an important role in hematogenous dissemination; and lipopolysaccharides that induce inflammatory responses. These studies demonstrate the contribution of a few factors in the pathogenesis of A. baumannii , suggesting that these mechanisms would be possible candidates for targets of novel antimicrobial agents.
Virulence factor blocking agents
Some studies have already been performed in order to investigate the role of blockers of A. baumannii virulence factors as potential antimicrobials. Several of them have focused on the inhibition of biofilm formation by different approaches, such as the use of a new phage (AB7-IBB2) that is able to lyze 49% of clinical isolates of A. baumannii , inhibit and disrupt the biofilm formation  ; other approaches are the use of...