From biofilm tolerance to antimicrobial resistance: molecular adaptation strategies and emerging therapeutic vulnerabilities in resistant pathogens
5 affiliations
- 1Department of Human Physiology, Vidyasagar University
- 2Centre for Life Sciences, Vidyasagar University
- 3Department of Chemistry, Vidyasagar University
- 4Department of Chemistry, Rani Rashmoni Green University
- 5Sadhu RamChand Murmu University of Jhargram
Abstract
Bacterial biofilms are highly structured microbial communities which allow organisms to persist under different environmental challenges such as limitation of nutrients, oxidative stress, host immune defense, and antimicrobial agents. While antimicrobial resistance (AMR) has been well recognized as a key factor contributing to treatment failure, more and more evidence reported that biofilm-associated persistence is initially caused by antimicrobial tolerance rather than genetically encoded resistance. Tolerance is a change in physiology that enables the bacterial population to persist through a temporary exposure to an antimicrobial agent, while resistance is a stable heritable alteration that confers a decreased susceptibility to an antimicrobial agent. In biofilms, the bacteria are distributed in a heterogeneous manner in different ecological niches with different metabolic activities, oxygen gradients, stress responses and nutrient accessibility. This heterogeneity gives rise to specialized subpopulations, including dormant persisters that serve as reservoirs for further evolutionary adaptation. Biofilm development results in a selective environment that allows the pressure of antimicrobial agents to induce molecular adaptation through remodelling of extracellular polymeric substance (EPS), metabolic reprogramming, oxidative stress management, quorum sensing, cyclic di-guanosine monophosphate (c-di-GMP) signaling, efflux activation, horizontal gene transfer and diversification via mutations. Such processes form a continuum of tolerance–resistance, with short-term survival processes potentially leading to the development and fixation of resistant phenotypes. Traditional antimicrobial strategies, mainly relying on planktonic susceptibility testing, fail in the resilience of biofilms, necessitating biofilm-specific therapeutic strategies. Here, we review an integrated framework that describes the way in which bacterial biofilms move from antimicrobial tolerance to resistance evolution. We focus on strategies to intercept biofilm adaptation before stable resistance is achieved, using a combination of evolutionary microbiology, molecular regulation, single-cell biology and therapeutic innovation.
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BibTeX
@article{guchhait2026from,
title = {{From biofilm tolerance to antimicrobial resistance: molecular adaptation strategies and emerging therapeutic vulnerabilities in resistant pathogens}},
author = {Kartik Chandra Guchhait and Subhamoy Dey and Sumita Rani Pradhan and Amiya Kumar Panda and Chandradipa Ghosh},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1988464},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1988464/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - From biofilm tolerance to antimicrobial resistance: molecular adaptation strategies and emerging therapeutic vulnerabilities in resistant pathogens
AU - Kartik Chandra Guchhait
AU - Subhamoy Dey
AU - Sumita Rani Pradhan
AU - Amiya Kumar Panda
AU - Chandradipa Ghosh
PY - 2026
DA - 2026/10/22
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1988464
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1988464/full
AB - Bacterial biofilms are highly structured microbial communities which allow organisms to persist under different environmental challenges such as limitation of nutrients, oxidative stress, host immune defense, and antimicrobial agents. While antimicrobial resistance (AMR) has been well recognized as a key factor contributing to treatment failure, more and more evidence reported that biofilm-associated persistence is initially caused by antimicrobial tolerance rather than genetically encoded resistance. Tolerance is a change in physiology that enables the bacterial population to persist through a temporary exposure to an antimicrobial agent, while resistance is a stable heritable alteration that confers a decreased susceptibility to an antimicrobial agent. In biofilms, the bacteria are distributed in a heterogeneous manner in different ecological niches with different metabolic activities, oxygen gradients, stress responses and nutrient accessibility. This heterogeneity gives rise to specialized subpopulations, including dormant persisters that serve as reservoirs for further evolutionary adaptation. Biofilm development results in a selective environment that allows the pressure of antimicrobial agents to induce molecular adaptation through remodelling of extracellular polymeric substance (EPS), metabolic reprogramming, oxidative stress management, quorum sensing, cyclic di-guanosine monophosphate (c-di-GMP) signaling, efflux activation, horizontal gene transfer and diversification via mutations. Such processes form a continuum of tolerance–resistance, with short-term survival processes potentially leading to the development and fixation of resistant phenotypes. Traditional antimicrobial strategies, mainly relying on planktonic susceptibility testing, fail in the resilience of biofilms, necessitating biofilm-specific therapeutic strategies. Here, we review an integrated framework that describes the way in which bacterial biofilms move from antimicrobial tolerance to resistance evolution. We focus on strategies to intercept biofilm adaptation before stable resistance is achieved, using a combination of evolutionary microbiology, molecular regulation, single-cell biology and therapeutic innovation.
SN - 1664-302X
ER -