The QseG Lipoprotein Impacts the Virulence of Enterohemorrhagic Escherichia coli and Citrobacter rodentium and Regulates Flagellar Phase Variation in Salmonella enterica Serovar Typhimurium

Abstract

The QseEF histidine kinase/response regulator system modulates expression of enterohemorrhagic <i>Escherichia coli</i> (EHEC) and <i>Salmonella enterica</i> serovar Typhimurium virulence genes in response to the host neurotransmitters epinephrine and norepinephrine. <i>qseG</i>, which encodes an outer membrane lipoprotein, is cotranscribed with <i>qseEF</i> in these enteric pathogens, but there is little knowledge of its role in virulence. Here, we found that in EHEC QseG interacts with the type III secretion system (T3SS) gate protein SepL and modulates the kinetics of attaching and effacing (AE) lesion formation on tissue-cultured cells. Moreover, an EHEC Δ<i>qseG</i> mutant had reduced intestinal colonization in an infant rabbit model. Additionally, in <i>Citrobacter rodentium</i>, an AE lesion-forming pathogen like EHEC, QseG is required for full virulence in a mouse model. In <i>S</i> Typhimurium, we found that QseG regulates the phase switch between the two flagellin types, FliC and FljB. In an <i>S</i> Typhimurium Δ<i>qseG</i> mutant, the phase-variable promoter for <i>fljB</i> is preferentially switched into the "on" position, leading to overproduction of this phase two flagellin. In infection of tissue-cultured cells, the <i>S</i> Typhimurium Δ<i>qseG</i> mutant provokes increased inflammatory cytokine production versus the wild type; <i>in vivo</i>, in a murine infection model, the Δ<i>qseG</i> strain caused a more severe inflammatory response and was attenuated versus the wild-type strain. Collectively, our findings demonstrate that QseG is important for full virulence in several enteric pathogens and controls flagellar phase variation in <i>S</i> Typhimurium, and they highlight both the complexity and conservation of the regulatory networks that control the virulence of enteric pathogens.