Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance.
Bacterial persistence refers to a state of reduced metabolic activity that endows a subpopulation of isogenic bacteria with multidrug tolerance. Persisters are phenotypic variants but not mutants. Since its discovery in 1944, bacterial persistence has not received enough attention until recently when its implications in persistent infections and biofilm infections become apparent. Much research has been done in recent years to investigate the mechanisms underlying bacterial persistence and phenotypic antibiotic resistance. The mechanisms of bacterial persistence are complex and the following pathways are involved in persister formation: toxin-antitoxin systems, reduced metabolism, energy production, protein and nucleic acid synthesis, DNA repair and protection, protein degradation, transporters/efflux systems, and transcriptional regulators etc. Although persistence mechanisms are conserved in terms of the gene function and pathways involved among different bacterial species, they may vary in gene homology and relative importance of a given pathway. For example, Escherichia coli toxin-antitoxin systems play an important role in persister formation, while Staphylococcus aureus persister formation does not appear to use toxin-antitoxin systems. Here we provide an update on recent progress in persistence mechanisms using E. coli and S. aureus as models, as well as discuss approaches in the treatment of persistent bacterial infections.
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Peng
P
Cui
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Tao
T
Xu
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
Wen-hong
WH
Zhang
1. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China; 2. Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore 21205, USA.
Ying
Y
Zhang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins