TisB enables antibiotic tolerance in Salmonella by preventing prophage induction through ATP depletion

  • Antibiotic persistence comprises drug-tolerant bacteria that can survive treatment with antibacterial agents, despite lacking classical genetic resistance mechanisms. Therefore, persisters are clinically relevant because they can lead to treatment failures and chronic infections. Additionally, antibiotic persistence facilitates the evolution of resistance through genetic mutations. Persisters are triggered by a lack of nutrients, bacterial toxins, low ATP levels, or other stress responses that shut down bacterial metabolism. However, the involvement of prophages, viruses that integrate into bacterial chromosomes, is less well understood. In this study, we tested a tisAB deletion in Salmonella Typhimurium and examined persister cell formation following treatment with the DNA-damaging drug ciprofloxacin. TisB is a bacterial toxin that increases the influx of protons across the inner bacterial membrane into the cytosol, causing ATP depletion. We demonstrate that the deletion of tisABAntibiotic persistence comprises drug-tolerant bacteria that can survive treatment with antibacterial agents, despite lacking classical genetic resistance mechanisms. Therefore, persisters are clinically relevant because they can lead to treatment failures and chronic infections. Additionally, antibiotic persistence facilitates the evolution of resistance through genetic mutations. Persisters are triggered by a lack of nutrients, bacterial toxins, low ATP levels, or other stress responses that shut down bacterial metabolism. However, the involvement of prophages, viruses that integrate into bacterial chromosomes, is less well understood. In this study, we tested a tisAB deletion in Salmonella Typhimurium and examined persister cell formation following treatment with the DNA-damaging drug ciprofloxacin. TisB is a bacterial toxin that increases the influx of protons across the inner bacterial membrane into the cytosol, causing ATP depletion. We demonstrate that the deletion of tisAB increases prophage induction and bacterial killing, leading to a reduced persister cell fraction. The tisAB mutant is unable to down regulate its ATP concentration after exposure to ciprofloxacin, which in turn allows for stronger binding of RecA to single-stranded DNA, the activator of both the SOS response and prophage induction.zeige mehrzeige weniger

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Metadaten
Autor*innen:S. Braetz, Niclas NordholtORCiD, A. Nerlich, Frank SchreiberORCiD, K. Tedin, M. Fulde
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):PLOS Pathogens
Jahr der Erstveröffentlichung:2025
Organisationseinheit der BAM:4 Material und Umwelt
4 Material und Umwelt / 4.1 Biologische Materialschädigung und Referenzorganismen
Ausgabe/Heft:9
Erste Seite:1
Letzte Seite:23
DDC-Klassifikation:Technik, Medizin, angewandte Wissenschaften / Ingenieurwissenschaften / Sanitär- und Kommunaltechnik; Umwelttechnik
Freie Schlagwörter:Antimicrobial resistance; Bacterial survival mechanisms; Escherichia coli; Salmonella typhimurium
Themenfelder/Aktivitätsfelder der BAM:Umwelt
Umwelt / Umwelt-Material-Interaktionen
DOI:10.1371/journal.ppat.1013498
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:13.11.2025
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:13.11.2025
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