is an important pathogen of nosocomial infection. Recently, a group of genes, named "" (for Growth in ), have been identified in a contemporary multi-drug resistant clinical isolate of -strain AB5075. Among these so-called genes, and were found to promote antibiotic resistance, stress survival, and virulence of AB5075 by interacting with the nitrogen phosphotransferase system (PTS). This study aimed to investigate the roles of /, 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 (encoding the Enzyme I component of the PTS) in the growth, stress resistance, and virulence of the widely studied strain ATCC 17978. Genetic analyses of strains harboring mutations of and were performed to investigate the roles of these genes in bacterial growth, stress resistance, evading macrophage defense, and killing of larva. In contrast with findings from strain AB5075 where and contribute to aminoglycoside resistance, the data presented herein indicate that the loss of does not impact antibiotic resistance of strain ATCC 17978. Interestingly, however, we found that deletion of 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 larvae. Importantly, studies as well as the loss of restored the phenotypes of the mutant to that of the wild-type. The data presented herein indicate that in ATCC 17978, the 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 stress-signaling pathway in two commonly studied isolates of this troublesome pathogen.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371402PMC
http://dx.doi.org/10.3389/fmicb.2021.723949DOI Listing

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