Acinetobacter baumannii: An Emerging Multidrug-resistant Threat

Thomas D Gootz; Andrea Marra

Disclosures

Expert Rev Anti Infect Ther. 2008;6(3):309-325. 

In This Article

Much less is known about A. baumannii virulence determinants than its antibiotic-resistance mechanisms. The most thorough analysis was a recent effort to sequence the genome of A. baumannii and compare it with its close relative, the nonpathogenic Acinetobacter baylyi. The findings were striking, mostly for the large amount of probable foreign DNA present in A. baumannii; 28 so-called putative alien islands were identified, based on differences in G plus C content and codon usage.[28] Homologs of virulence genes identified in other pathogens were found in 12 of these islands and the largest island contained genes for a putative type IV secretion apparatus. Other islands harbor genes for antibiotic-resistance determinants, an indication that A. baumannii has a high capacity to take in and incorporate foreign DNA. The comparison with A. baylyi was also illuminating since A. baylyi is noted for its remarkable natural transformability and the ease with which it is able to express foreign genes.[52,53] It was found that the A. baumannii genome contains most of the genes involved in competence and homologs were found that may compensate for the two that it lacks. This finding may account for the large amount of foreign DNA present and, in addition, could indicate that A. baumannii is also capable of natural transformation under certain conditions, albeit not to the same degree as A. baylyi.

So far, only a few factors of A. baumannii have demonstrated a role in virulence. An outer membrane protein called Omp38 has been shown to cause apoptosis in cultured cells,[54] although it is not yet clear what effect this protein has during human infection. The exopolysaccharide produced by A. baumannii has also been implicated in virulence as a means of protection from the host immune response and as a factor in biofilm formation[55]; approximately 30% of A. baumannii isolates produce exopolysaccharide; approximately 30% of A. baumannii isolates produce exopolysaccharide.[56]A. baumannii is able to form biofilms despite its lack of flagella (pili have been cited as important for biofilm formation and cell adhesion).[55,57] Adherence of A. baumannii to red blood cells and human bronchial epithelial cells in culture has been demonstrated,[57] although no difference in cell binding was observed between outbreak strains and environmental isolates. A unique iron uptake system, also important for virulence, has been identified in A. baumannii[58] and is consistent with the finding that A. baumannii is able to grow under iron-limiting conditions.[59] In in vitro assays, it has been shown that low iron conditions favor A. baumannii biofilm formation[55]; this finding is consistent with the fact that A. baumannii is likely to encounter low iron conditions during host infection.

Mouse models of A. baumannii infection have been used to study host responses to this pathogen. Most are a variation of a pulmonary infection, using either intranasal or intratracheal instillation to initiate infection.[60,61] Such studies have found that upon infection, there was rapid neutrophil recruitment to the lungs (within 4 h), which declined once the bacteria were cleared.[60] When neutrophils were depleted, the infection was much more acute and lethal, with increased bacterial burdens and bacterial spread to the spleen. The finding that neutrophils play a major role in host response in the lungs to A. baumannii infection, if found to be true for humans, could explain the incidence and severity of infections in immunocompromised patients and could help guide therapeutic intervention.

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