Dataset Information

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance.

ABSTRACT: Recent laboratory evolution studies have shown that upon repetitive antibiotic treatments, bacterial populations will adapt and eventually became tolerant and resistant to the drug. Drug tolerance rapidly evolves upon frequent, intermittent antibiotic treatments, and such emerging drug tolerance seems to be specific to the treatment conditions, complicating clinical practice. Moreover, it has been shown that tolerance often promotes the development of resistance, which further reinforces the need of clinical diagnostics for antibiotic tolerance to reduce the occurrence of acquired resistance. Here, we discuss the laboratory evolution studies that were performed to track the development of tolerance in bacterial populations, and highlight the urgency of developing a comprehensive knowledge base of various tolerance phenotypes and their detection in clinics. Finally, we propose future directions for basic research in this growing field.

SUBMITTER: Sulaiman JE

PROVIDER: S-EPMC7952611 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance.

Sulaiman Jordy Evan JE Lam Henry H

Frontiers in microbiology 20210226

Recent laboratory evolution studies have shown that upon repetitive antibiotic treatments, bacterial populations will adapt and eventually became tolerant and resistant to the drug. Drug tolerance rapidly evolves upon frequent, intermittent antibiotic treatments, and such emerging drug tolerance seems to be specific to the treatment conditions, complicating clinical practice. Moreover, it has been shown that tolerance often promotes the development of resistance, which further reinforces the nee ...[more]

PMID: 33717007

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Project description:The widespread use of antibiotics promotes the evolution and dissemination of resistance and tolerance mechanisms. To assess the relevance of tolerance and its implications for resistance development, we used in vitro evolution and analyzed the inpatient microevolution of Pseudomonas aeruginosa, an important human pathogen causing acute and chronic infections. We show that the development of tolerance precedes and promotes the acquisition of resistance in vitro, and we present evidence that similar processes shape antibiotic exposure in human patients. Our data suggest that during chronic infections, P. aeruginosa first acquires moderate drug tolerance before following distinct evolutionary trajectories that lead to high-level multidrug tolerance or to antibiotic resistance. Our studies propose that the development of antibiotic tolerance predisposes bacteria for the acquisition of resistance at early stages of infection and that both mechanisms independently promote bacterial survival during antibiotic treatment at later stages of chronic infections.IMPORTANCE Over the past decades, pan-resistant strains of major bacterial pathogens have emerged and have rendered clinically available antibiotics ineffective, putting at risk many of the major achievements of modern medicine, including surgery, cancer therapy, and organ transplantation. A thorough understanding of processes leading to the development of antibiotic resistance in human patients is thus urgently needed. We show that drug tolerance, the ability of bacteria to survive prolonged exposure to bactericidal antibiotics, rapidly evolves in the opportunistic human pathogen Pseudomonas aeruginosa upon recurrent exposures to antibiotics. Our studies show that tolerance protects P. aeruginosa against different classes of antibiotics and that it generally precedes and promotes resistance development. The rapid evolution of tolerance during treatment regimens may thus act as a strong driving force to accelerate antibiotic resistance development. To successfully counter resistance, diagnostic measures and novel treatment strategies will need to incorporate the important role of antibiotic tolerance.

Dataset Information

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance.

Publications

Evolution of Bacterial Tolerance Under Antibiotic Treatment and Its Implications on the Development of Resistance.

Similar Datasets

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