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Acinetobacter baumannii  is an important pathogen of nosocomial infection. Recently, a group of genes, named “ gig ” (for  G rowth  i n   G alleria ), have been identified in a contemporary multi-drug resistant clinical isolate of  A. baumannii —strain AB5075. Among these so-called  gig  genes,  gigA  and  gigB  were found to promote antibiotic resistance, stress survival, and virulence of AB5075 by interacting with the nitrogen phosphotransferase system (PTS Ntr ). This study aimed to investigate the roles of  gigA / gigB , which appear to comprise a stress-signaling pathway (encoding for an atypical two-component system response regulator and a predicted anti-anti-sigma factor, respectively), and the involvement of  ptsP  (encoding the Enzyme I component of the PTS Ntr ) in the growth, stress resistance, and virulence of the widely studied  A. baumannii  strain ATCC 17978. Genetic analyses of strains harboring mutations of  gigA  and  gigB  were performed to investigate the roles of these genes in bacterial growth, stress resistance, evading macrophage defense, and killing of  Galleria mellonella  larva. In contrast with findings from strain AB5075 where  gigA  and  gigB  contribute to aminoglycoside resistance, the data presented herein indicate that the loss of  gigA/gigB  does not impact antibiotic resistance of strain ATCC 17978. Interestingly, however, we found that deletion of  gigA/gigB  in the ATCC 17978 background imparts a general growth in laboratory medium and also conferred growth and replication defects within murine macrophages and an inability to kill  G. mellonella  larvae. Importantly, studies as well as the loss of  ptsP  restored the phenotypes of the  gigA/gigB  mutant to that of the wild-type. The data presented herein indicate that in  A. baumannii  ATCC 17978, the  gigA/gigB  genes play a key role in both growth and virulence traits, but are dispensable for other stress-resistance survival phenotypes, including aminoglycoside resistance. Our findings thus highlight several similarities and also important differences between the  gigA/gigB  stress-signaling pathway in two commonly studied isolates of this troublesome pathogen.

The gigA/gigB Genes Regulate the Growth, Stress Response, and Virulence of Acinetobacter baumannii ATCC 17978 Strain