The BaeS/BaeR two-component system enhancesintestinal colonization by upregulating.
Source: PubMed, NCBI / U.S. National Library of Medicine
relies on two-component signal transduction systems to adapt to the host intestinal microenvironment. This study investigated the role and regulatory mechanism of the BaeS/BaeR two-component system in intestinal colonization and antimicrobial peptide resistance. Adeletion mutant and complemented strain were constructed in the O1 El Tor clinical isolate EL2382. Intestinal colonization, Caco-2 cell adhesion, histopathological analysis, transcriptomic profiling, qRT-PCR, western blotting, electrophoretic mobility shift assays, chromatin immunoprecipitation-qPCR, and antimicrobial peptide resistance assays were performed. Expression of baeS and baeR was markedly induced during intestinal colonization and adhesion to Caco-2 cells. Themutant exhibited significantly impaired bacterial adhesion andcolonization, accompanied by reduced histopathological scores, and these phenotypes were restored by genetic complementation. Transcriptomic analysis identified(VC2553), which encodes an ABC transporter involved in antimicrobial peptide homeostasis, as a key downstream target of BaeS/BaeR. BaeR bound to thepromoter and activated its transcription, and deletion-mapping electrophoretic mobility shift assays localized a putative BaeR-responsive sequence to 5'-TTCTTTTT-3' within the -10/-35 spacer region. Similar to themutant, themutant exhibited reduced resistance to human defensin 5 and impaired intestinal colonization. L-arginine exposure was associated with dose-dependent activation of the
Abstract
relies on two-component signal transduction systems to adapt to the host intestinal microenvironment. This study investigated the role and regulatory mechanism of the BaeS/BaeR two-component system in intestinal colonization and antimicrobial peptide resistance. Adeletion mutant and complemented strain were constructed in the O1 El Tor clinical isolate EL2382. Intestinal colonization, Caco-2 cell adhesion, histopathological analysis, transcriptomic profiling, qRT-PCR, western blotting, electrophoretic mobility shift assays, chromatin immunoprecipitation-qPCR, and antimicrobial peptide resistance assays were performed. Expression of baeS and baeR was markedly induced during intestinal colonization and adhesion to Caco-2 cells. Themutant exhibited significantly impaired bacterial adhesion andcolonization, accompanied by reduced histopathological scores, and these phenotypes were restored by genetic complementation. Transcriptomic analysis identified(VC2553), which encodes an ABC transporter involved in antimicrobial peptide homeostasis, as a key downstream target of BaeS/BaeR. BaeR bound to thepromoter and activated its transcription, and deletion-mapping electrophoretic mobility shift assays localized a putative BaeR-responsive sequence to 5'-TTCTTTTT-3' within the -10/-35 spacer region. Similar to themutant, themutant exhibited reduced resistance to human defensin 5 and impaired intestinal colonization. L-arginine exposure was associated with dose-dependent activation of the BaeS/BaeR pathway and BaeS/BaeR-dependent induction of, although a direct physical interaction between L-arginine and BaeS was not established. These findings identify an L-arginine-associated BaeS/BaeR-SalX regulatory pathway that promotes antimicrobial peptide resistance and intestinal colonization by, providing new insight into host cue-associated regulation of bacterial colonization fitness.