title: AnompR-envZTwo-Component System Ortholog Regulates Phase Variation, Osmotic Tolerance, Motility, and Virulence in Acinetobacter baumannii Strain AB5075.
abstract: Recently, a novel phase-variable colony opacity phenotype was discovered inAcinetobacter baumanniistrain AB5075, where colonies interconvert between opaque and translucent variants. Opaque colonies become mottled or sectored after 24 h of growth due to translucent variants arising within the colony. This easily distinguishable opaque-colony phenotype was used to screen for random transposon insertions that increased the frequency of sectoring at a time point when wild-type colonies were uniformly opaque. A colony was identified that contained multiple papillae of translucent variants, and the insertion in this mutant mapped to an ortholog of the two-component system response regulatorompRSubsequent investigation of in-frame deletions ofompRand the sensor kinaseenvZ(located adjacent toompR) showed that the switching frequency from opaque to translucent was increased 401- and 281-fold, respectively. TheompRmutant also exhibited sensitivity to sodium chloride in growth medium, whereas theenvZmutation did not elicit sensitivity to sodium chloride. Mutation of either gene reduced motility inA. baumanniistrain AB5075, but a mutation in bothompRandenvZproduced a more profound effect. TheompRandenvZgenes were cotranscribed but were not subject to autoregulation by OmpR. BothompRandenvZmutant opaque variants were attenuated in virulence in theGalleria mellonellainfection model, whereas mutation ofompRhad no effect on the virulence of the translucent variant.IMPORTANCEAcinetobacter baumanniiis a well-known antibiotic-resistant pathogen; many clinical isolates can only be treated by a very small number of antibiotics (including colistin), while some exhibit panresistance. The current antimicrobial arsenal is nearing futility in the treatment ofAcinetobacterinfections, and new avenues of treatment are profoundly needed. Since phase variation controls the transition between opaque (virulent) and translucent (avirulent) states inA. baumannii, this may represent an "Achilles' heel" that can be targeted via the development of small molecules that lock cells in the translucent state and allow the host immune system to clear the infection. A better understanding of how phase variation is regulated may allow for the development of methods to target this process. TheompR-envZtwo-component system ortholog negatively regulates phase variation inA. baumannii, and perturbation of this system leads to the attenuation of virulence in an invertebrate infection model.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Tipton
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA prather@emory.edu.|Research Service, Atlanta VA Medical Center, Decatur, Georgia, USA.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Rather
keywords: Acinetobacter; osmotic stress; phase variation