Abstract
Acinetobacter baumannii is a multidrug-resistant, Gram-negative nosocomial pathogen that exhibits phenotypic heterogeneity resulting in virulent opaque (VIR-O) and avirulent translucent (AV-T) colony variants. Each variant has a distinct gene expression profile resulting in multiple phenotypic differences. Cells interconvert between the VIR-O and AV-T variants at high frequency under laboratory conditions, suggesting that the genetic mechanism underlying the phenotypic switch could be manipulated to attenuate virulence. Therefore, our group has focused on identifying and characterizing genes that regulate this switch, which led to the investigation of ABUW_1132 (1132), a highly conserved gene predicted to encode a LysR-type transcriptional regulator. ABUW_1132 was shown to be a global regulator as the expression of 74 genes was altered ≥ 2-fold in an 1132 deletion mutant. The 1132 deletion also resulted in a 16-fold decrease in VIR-O to AV-T switching, loss of 3-OH-C12-HSL secretion, and reduced surface-associated motility. Further, the deletion of 1132 in the AV-T background caused elevated capsule production, which increased colony opacity and altered the typical avirulent phenotype of translucent cells. These findings distinguish 1132 as a global regulatory gene and advance our understanding of A. baumannii’s opacity-virulence switch.
Highlights
The Gram-negative pathogen Acinetobacter baumannii poses a major threat to hospitalized patients
Genes that encode ribosomal proteins, RNA polymerase, translation initiation factors, and both transcriptional and translational elongation factors are among genes that are upregulated in virulent opaque (VIR-O) D1132
Our work demonstrates that an 1132 deletion, and possibly its natural downregulation, has the potential to increase virulence of the typically avirulent translucent colony variant in the clinical isolate AB5075
Summary
The Gram-negative pathogen Acinetobacter baumannii poses a major threat to hospitalized patients. A. baumannii’s rapidly growing resistance to carbapenem antibiotics and its ability to widely disseminate resistance via mobile genetic elements prompted the World Health Organization to name this organism as a critical priority for the research and development of new antimicrobial drugs in 2017 (World Health Organization, 2017). In the face of such problematic phenotypes, an understanding of pathogenesis and virulence in this species is imperative. To meet this need, experiments conducted by our group have been carried out in the strain AB5075 (GenBank Accession Number CP008706.1), a highly virulent MDR clinical isolate that is genetically tractable (Jacobs et al, 2014; Gallagher et al, 2015)
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