The Ethanolamine Permease EutH Promotes Vacuole Adaptation of Salmonella enterica and Listeria monocytogenes during Macrophage Infection

Abstract

Ethanolamine is a ubiquitous and essential molecule within a host. Significantly, bacterial pathogens exploit ethanolamine during infection to promote growth and regulate virulence. The ethanolamine permease EutH is dispensable for growth under standard conditions, whereas EutH is required for ethanolamine utilization at low pH. These findings suggested a model in which EutH facilitates diffusion of ethanolamine into the bacterial cell in acidic environments. To date, the ecological significance of this model has not been thoroughly investigated, and the importance of EutH to bacterial growth under physiologically relevant conditions is not known. During infection, immune cells internalize invading bacteria within an acidic, nutrient-depleted vacuole called the phagosome. Here, we investigated the hypothesis that EutH promotes bacterial survival following phagocytosis. Our findings indicate that EutH is important for survival and replication of the facultative intracellular pathogens serovar Typhimurium and during prolonged or transient exposure to the phagosome, respectively. Furthermore, in agreement with EutH being important in the acidic environment, neutralization of the vacuole abolished the requirement for EutH. Significantly, consistent with a role for EutH in promoting intramacrophage survival, EutH was not required during Typhimurium local intestinal infection but specifically conferred an advantage upon dissemination to peripheral organs. These findings reveal a physiologically relevant and conserved role for EutH in spatiotemporal niche adaptation during infection.

Ethanolamine Influences Human Commensal Escherichia coli Growth, Gene Expression, and Competition with Enterohemorrhagic E. coli O157:H7

“…EA utilization plays a central role in host adaptation for a diverse range of pathogens, including opportunistic pathogens ( 3 , 4 ). EA can serve as a carbon, nitrogen, and/or energy source to promote growth as well as a signal to influence virulence during host infection ( 5 – 11 ). Genes encoding EA utilization are carried in the e thanolamine ut ilization ( eut ) locus ( 12 ).…”

Parallel quorum-sensing system in Vibrio cholerae prevents signal interference inside the host

“…Some bacteria also sense ethanolamine outside of the GI tract to regulate gene expression [44,[59][60][61][62]. In addition, previous studies have demonstrated that ethanolamine utilization can both positively and negatively affect host colonization and virulence during infection [44,46,55,[59][60][61][62][63]. We and others [47], showed that certain Vibrios are unable to metabolize ethanolamine as either carbon or nitrogen source, nevertheless, the influence of ethanolamine on virulence gene expression can be independent of ethanolamine metabolism [44,57].…”

“…Although we cannot rule out molecules present in the GI tract other than ethanolamine can also act on CqsR, other enteric pathogens including E. coli, Salmonella, Enterococcus, and C. difficile have adopted different mechanisms to sense this common metabolite to regulate their gene expression to improve their fitness inside the host [44,46,[55][56][57][58]. Some bacteria also sense ethanolamine outside of the GI tract to regulate gene expression [44,[59][60][61][62]. In addition, previous studies have demonstrated that ethanolamine utilization can both positively and negatively affect host colonization and virulence during infection [44,46,55,[59][60][61][62][63].…”

The Cobalamin-Dependent Gene Cluster of Listeria monocytogenes: Implications for Virulence, Stress Response, and Food Safety

“…However, the majority of L. monocytogenes cells remains confined to the phagosome 2-3 h post-infection (de Chastellier and Berche, 1994;Singh et al, 2008). Anderson et al (2018) also proposed that there may be a functional link between LLO and EutH; however, a hypothesis that suggests a function was not proposed in the study. These findings highlight the importance of EutH for the survival and replication of L. monocytogenes in macrophages in response to vacuole acidification.…”

“…However, EA is protonated in acid conditions and requires the EA permease, EutH, to be internalized by L. monocytogenes. Anderson et al (2018) elucidated that EutH is important for the intracellular survival and replication of S. Typhimurium and L. monocytogenes. EutH did not promote intestinal infection but instead provides a crucial advantage in the dissemination of L. monocytogenes to the liver and spleen.…”