The vulnerable versatility of Salmonella antibiotic persisters during infection

Cell Host Microbe. 2021 Dec 8;29(12):1757-1773.e10. doi: 10.1016/j.chom.2021.10.002. Epub 2021 Nov 2.


Tolerance and persistence are superficially similar phenomena by which bacteria survive bactericidal antibiotics. It is assumed that the same physiology underlies survival of individual tolerant and persistent bacteria. However, by comparing tolerance and persistence during Salmonella Typhimurium infection, we reveal that these two phenomena are underpinned by different bacterial physiologies. Multidrug-tolerant mutant Salmonella enter a near-dormant state protected from immune-mediated genotoxic damages. However, the numerous tolerant cells, optimized for survival, lack the capabilities necessary to initiate infection relapse following antibiotic withdrawal. In contrast, persisters retain an active state. This leaves them vulnerable to accumulation of macrophage-induced dsDNA breaks but concurrently confers the versatility to initiate infection relapse if protected by RecA-mediated DNA repair. Accordingly, recurrent, invasive, non-typhoidal Salmonella clinical isolates display hallmarks of persistence rather than tolerance during antibiotic treatment. Our study highlights the complex trade-off that antibiotic-recalcitrant Salmonella balance to act as a reservoir for infection relapse.

Keywords: DNA; DNA damage; Salmonella; antibiotic persistence; antibiotic tolerance; host-pathogen interactions; relapsing infection; repair.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • DNA Breaks, Double-Stranded / drug effects
  • DNA Damage / drug effects
  • DNA Repair
  • Drug Resistance, Multiple, Bacterial
  • Drug Tolerance
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Immune Tolerance / drug effects
  • Macrophages / drug effects
  • Mice, Inbred C57BL
  • Plant Leaves
  • Rec A Recombinases
  • Recurrence
  • Salmonella typhimurium / drug effects*
  • Transcriptome
  • Whole Genome Sequencing


  • Anti-Bacterial Agents
  • Rec A Recombinases