Link Between Antibiotic Persistence and Antibiotic Resistance in Bacterial Pathogens

Abstract

Both, antibiotic persistence and antibiotic resistance characterize phenotypes of survival in which a bacterial cell becomes insensitive to one (or even) more antibiotic(s). However, the molecular basis for these two antibiotic-tolerant phenotypes is fundamentally different. Whereas antibiotic resistance is genetically determined and hence represents a rather stable phenotype, antibiotic persistence marks a transient physiological state triggered by various stress-inducing conditions that switches back to the original antibiotic sensitive state once the environmental situation improves. The molecular basics of antibiotic resistance are in principle well understood. This is not the case for antibiotic persistence. Under all culture conditions, there is a stochastically formed, subpopulation of persister cells in bacterial populations, the size of which depends on the culture conditions. The proportion of persisters in a bacterial population increases under different stress conditions, including treatment with bactericidal antibiotics (BCAs). Various models have been proposed to explain the formation of persistence in bacteria. We recently hypothesized that all physiological culture conditions leading to persistence converge in the inability of the bacteria to re-initiate a new round of DNA replication caused by an insufficient level of the initiator complex ATP-DnaA and hence by the lack of formation of a functional orisome. Here, we extend this hypothesis by proposing that in this persistence state the bacteria become more susceptible to mutation-based antibiotic resistance provided they are equipped with error-prone DNA repair functions. This is - in our opinion - in particular the case when such bacterial populations are exposed to BCAs.

Enhanced Antimicrobial Activity through Synergistic Effects of Cold Atmospheric Plasma and Plant Secondary Metabolites: Opportunities and Challenges

“…Persistence refers to the ability of a small subset of bacteria to survive exposure to antibiotics but not multiply [24]; these bacteria are not killed by the antibiotics but instead enter a dormant state called a persistent phenotype and can be reawakened later when the antibiotic pressure is reduced. This is a survival mechanism that allows bacteria to persist in the presence of antibiotics and can contribute to the development of chronic infections and antibiotic resistance [25,26]. Both persistence and resistance can contribute to the failure of antibiotics to cure infections and the spread of antibiotic-resistant bacteria [27].…”

Defying the odds: Determinants of the antimicrobial response of Salmonella Typhi and their interplay

“…Induction of an SOS response by bactericidal antibiotics such as β‐lactams and fluroquinolones can induce the expression of genes responsible for conjugative transfer in suitable donor bacteria such as S. enterica , V. cholerae and S. aureus . This increases the frequency of transfer of plasmids, transposons, integrons and lysogenic phages harbouring the antibiotic resistance genes between the donor and recipient bacteria (Bearson & Brunelle, 2015; Blazquez et al., 2018; Eisenreich et al., 2022; Hebrard et al., 2009; Liu et al., 2017; Maiques et al., 2006). From these studies, we can infer that bacterial antibiotic persistence may be an understudied and unexplored cause of AMR.…”

RBProkCNN: Deep learning on appropriate contextual evolutionary information for RNA binding protein discovery in prokaryotes

“…While the historical emphasis has been on eukaryotic RBPs, recent investigations have brought to light the critical significance of their prokaryotic counterparts [6] , [7] , [8] . By acting as a regulator of various cellular processes and playing crucial role in sculpting the dynamic landscape of bacterial gene expression, prokaryotic RBPs contribute significantly to the adaptation of prokaryotes across diverse environmental conditions [9] , [10] . A noteworthy aspect of prokaryotic RBPs further lies in their participation in governing bacterial virulence and pathogenicity, pinpointing potential targets for novel antibiotic development [11] , [12] , [13] , [14] , [15] .…”