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

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.

Ultrasonic cavitation induced Vibrio parahaemolyticus entering an apoptosis-like death process through SOS response

“…Two-component systems of bacteria play an important role in adapting to new environmental conditions by sensing environmental signals and regulating the expression of certain genes [32] . OmpF and OmpC are two major pore proteins in the outer membrane of bacteria, through which hydrophilic substances can enter the cell.…”

Hyperphosphorylation of the Group A Streptococcal Control of Virulence Regulator Increases Promoter Occupancy Specifically at Virulence Factor-Encoding Genes

“…Two-component signaling pathways are critical to bacterial pathogenesis and thus remain a highly active area of investigation across a broad array of major human pathogens ( 61 – 63 ). Herein, we delineate the global binding characteristics of the critical streptococcal response regulator CovR, in both a wild-type emm3 GAS and a CovS phosphatase-inactive strain.…”

The Yin and Yang of pathogens and probiotics: interplay between Salmonella enterica sv. Typhimurium and Bifidobacterium infantis during co-infection

“…Many studies have sought to unravel the individual effect of probiotics, commensals, or pathogens on the host, but probiotic-pathogen interactions at the host interface remains an understudied field that is being complicated by the genomic variation of Salmonella ( Gupta et al, 2019 ), strain variation in bifidobacteria ( LoCascio et al, 2010 ; Díaz et al, 2021 ), and the variation in ecology of the gut between age groups ( Voreades et al, 2014 ; Laforest-Lapointe and Arrieta, 2017 ). A steady increase in literature suggesting interspecies communication (i.e., community cross talk) exerts some control over the expression of virulence genes in enteric pathogens further highlights the need to define biochemical and genomic underpinnings of these interactions ( Kendall and Sperandio, 2007 ; Shaw et al, 2022 ). The modulation of microbial activity by neighboring gut microbes via chemical signaling, for instance by widely conserved quorum response transcription factor sdiA in Salmonella ( Plitnick et al, 2021 ), suggests microbe-microbe interactions via small metabolites are a significant factor in the infection process of enteric pathogens and potentially also in the response to probiotic interactions ( Thompson et al, 2016 ).…”