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Review

Two-component systems regulate bacterial virulence in response to the host gastrointestinal environment and metabolic cues

ORCID Icon, ORCID Icon & ORCID Icon
Pages 1666-1680 | Received 05 Apr 2022, Accepted 18 Sep 2022, Published online: 24 Sep 2022
 

ABSTRACT

Two-component systems are ubiquitous signaling mechanisms in bacteria that enable intracellular changes from extracellular cues. These bacterial regulatory systems couple external stimuli to control genetic expression via an autophosphorylation cascade that transduces membrane signals to intracellular locations, thereby allowing bacteria to rapidly adapt to the changing environmental conditions. Well known to control basic cellular processes, it is evident that two-component systems also exercise control over virulence traits, such as motility, secretion systems, and stress responses that impact the complex cascade of networks that alter virulence traits. In the gastrointestinal system, cues for activation of virulence-related two-component systems include metal ions, host-derived metabolites, and gut conditions. The diversity and origin of these cues suggest that the host can exert control over enteric pathogenicity via regulation in the gastrointestinal system. With the rise in multi-drug resistant pathogens, the potential control of pathogenicity with host cues via two-component systems presents a potential alternative to antimicrobials. Though the signaling mechanism itself is well studied, to date there is no systematic review compiling the host-associated cues of two-component systems and virulence traits. This review highlights the direct link between the host gastrointestinal environment and pathogenicity by focusing on two-component systems that are associated with the genetic expression of virulence traits, and that are activated by host-derived cues. The direct link between the host gastrointestinal environment, metabolites, and pathogenicity established in this review both underscores the importance of host-derived cues on bacterial activity and presents an enticing therapeutic target in the fight against antimicrobial resistant pathogens.

Author contribution

CS = conception, write manuscript, edit; MH = conception, write manuscript, edit; BCW = conception, write manuscript, edit

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

All the underlying data were derived from the literature. The analysis for metagenomes were done using publicly available sequences from IMG-M (https://img.jgi.doe.gov/) and described by Nayfach et al. 2020 (DOI:10.1038/s41587-020-0718-6).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.