title: The Hha-TomB Toxin-Antitoxin System Shows Conditional Toxicity and Promotes Persister Cell Formation by Inhibiting Apoptosis-Like Death in S. Typhimurium.
abstract: Toxin-antitoxin (TA) modules are two component "addictive" genetic elements found on either plasmid or bacterial chromosome, sometimes on both. TA systems perform a wide range of functions like biofilm formation, persistence, programmed cell death, phage abortive infection etc. Salmonella has been reported to contain several such TA systems. However, the hemolysin expression modulating protein (Hha) and its adjacent uncharacterized hypothetical protein TomB (previously known as YbaJ), have not been listed as a TA module in Salmonella. In this study we established that Hha and TomB form a bonafide TA system where Hha serves as a toxin while TomB functions as an antitoxin. Interestingly, the toxicity of Hha was conditional causing cell death under acid stress. The antitoxin attenuated the toxicity of Hha by forming a TA complex through stable interactions. The Hha-TomB TA system was found to increase persistence and inhibit programmed cell death under antibiotic stress where a phenotypically diverse population expressing differential level of TA components was observed. Therefore we propose that Hha and TomB prevent cells from committing suicide thereby promoting persister cell formation.
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Prajita
authors.initials: P
authors.lastname: Paul
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Padhi
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Ray
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ryan
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Shantoshini
authors.initials: S
authors.lastname: Dash
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar-751024, Odisha, India.
authors.forename: Mrutyunjay
authors.initials: M
authors.lastname: Suar
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D012486:Salmonella typhimurium / Q000502:physiology*; D000075704:Toxin-Antitoxin Systems / Q000502:physiology*