start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=5
article-no=
start-page=e00824-24
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250527
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Sodium butyrate inhibits the expression of virulence factors in Vibrio cholerae by targeting ToxT protein
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cholera, a diarrheal disease caused by the gram-negative bacterium Vibrio cholerae, remains a global health threat in developing countries due to its high transmissibility and increased antibiotic resistance. There is a pressing need for alternative strategies, with an emphasis on anti-virulent approaches to alter the outcome of bacterial infections, given the increase in antimicrobial-resistant strains. V. cholerae causes cholera by secreting virulence factors in the intestinal epithelial cells. These virulence factors facilitate bacterial colonization and cholera toxin production during infection. Here, we demonstrate that sodium butyrate (SB), a small molecule, had no effect on bacterial viability but was effective in suppressing the virulence attributes of V. cholerae. The production of cholera toxin (CT) was significantly reduced in a standard V. cholerae El Tor strain and two clinical isolates when grown in the presence of SB. Analysis of mRNA and protein levels further revealed that SB reduced the expression of the ToxT-dependent virulence genes like tcpA and ctxAB. DNA-protein interaction assays, conducted at cellular (ChIP) and in vitro conditions (EMSA), indicated that SB weakens the binding between ToxT and its downstream promoter DNA, likely by blocking DNA binding. Furthermore, the anti-virulence efficacy of SB was confirmed in animal models. These findings suggest that SB could be developed as an anti-virulence agent against V. cholerae, serving as a potential alternative to conventional antibiotics or as an adjunctive therapy to combat cholera.
en-copyright=
kn-copyright=

en-aut-name=KunduSushmita
en-aut-sei=Kundu
en-aut-mei=Sushmita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=DasSuman
en-aut-sei=Das
en-aut-mei=Suman
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MaitraPriyanka
en-aut-sei=Maitra
en-aut-mei=Priyanka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HalderProlay
en-aut-sei=Halder
en-aut-mei=Prolay
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KoleyHemanta
en-aut-sei=Koley
en-aut-mei=Hemanta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MukhopadhyayAsish K.
en-aut-sei=Mukhopadhyay
en-aut-mei=Asish K.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MiyoshiShin-ichi
en-aut-sei=Miyoshi
en-aut-mei=Shin-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=DuttaShanta
en-aut-sei=Dutta
en-aut-mei=Shanta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ChatterjeeNabendu Sekhar
en-aut-sei=Chatterjee
en-aut-mei=Nabendu Sekhar
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=BhattacharyaSushmita
en-aut-sei=Bhattacharya
en-aut-mei=Sushmita
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=2
en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=3
en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=4
en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=5
en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=6
en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=7
en-affil=Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Division of Bacteriology, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=9
en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=

affil-num=10
en-affil=Division of Biochemistry, ICMR-National Institute for Research in Bacterial Infections (Formerly ICMR-National Institute of Cholera and Enteric Diseases)
kn-affil=
en-keyword=sodium butyrate (SB)
kn-keyword=sodium butyrate (SB)
en-keyword=inhibitor
kn-keyword=inhibitor
en-keyword=pathogenesis
kn-keyword=pathogenesis
en-keyword=Vibrio cholerae
kn-keyword=Vibrio cholerae
en-keyword=ctxAB
kn-keyword=ctxAB
en-keyword=antimicrobial resistance
kn-keyword=antimicrobial resistance
en-keyword=toxin-coregulated pilus (TcpA)
kn-keyword=toxin-coregulated pilus (TcpA)
END