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Population and Single-Cell Analysis of Antibiotic Persistence in Escherichia coli
Published on: March 24, 2023
Antibiotic resistance and persistence-Implications for human health and treatment perspectives
Markus Huemer1, Srikanth Mairpady Shambat1, Silvio D Brugger1
1Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Abstract:
Antimicrobial resistance (AMR) and persistence are associated with an elevated risk of treatment failure and relapsing infections. They are thus important drivers of increased morbidity and mortality rates resulting in growing healthcare costs. Antibiotic resistance is readily identifiable with standard microbiological assays, and the threat imposed by antibiotic resistance has been well recognized. Measures aiming to reduce resistance development and spreading of resistant bacteria are being enforced. However, the phenomenon of bacteria surviving antibiotic exposure despite being fully susceptible, so-called antibiotic persistence, is still largely underestimated. In contrast to antibiotic resistance, antibiotic persistence is difficult to measure and therefore often missed, potentially leading to treatment failures. In this review, we focus on bacterial mechanisms allowing evasion of antibiotic killing and discuss their implications on human health. We describe the relationship between antibiotic persistence and bacterial heterogeneity and discuss recent studies that link bacterial persistence and tolerance with the evolution of antibiotic resistance. Finally, we review persister detection methods, novel strategies aiming at eradicating bacterial persisters and the latest advances in the development of new antibiotics.
Insights
Antibiotic resistance and persistence increase treatment failures and healthcare costs. This review explores bacterial survival mechanisms, their link to resistance, and new strategies to combat these persistent infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- Antimicrobial resistance (AMR) and antibiotic persistence contribute to treatment failures, relapsing infections, and increased morbidity and mortality.
- While antibiotic resistance is well-recognized and monitored, antibiotic persistence is often underestimated due to measurement difficulties, leading to missed diagnoses and treatment failures.
- Understanding bacterial survival mechanisms is crucial for addressing the growing threat of untreatable infections and rising healthcare expenditures.
Purpose of the Study:
- To review bacterial mechanisms enabling survival during antibiotic exposure (persistence).
- To discuss the relationship between antibiotic persistence, bacterial heterogeneity, and the evolution of antibiotic resistance.
- To explore current and novel strategies for detecting and eradicating bacterial persisters and advancing antibiotic development.
Main Methods:
- Literature review of studies on bacterial persistence, tolerance, and resistance.
- Analysis of mechanisms underlying bacterial survival against antibiotics.
- Examination of the link between persistence and the development of antibiotic resistance.
- Review of persister detection methods and therapeutic strategies.
Main Results:
- Bacterial persistence, distinct from resistance, allows survival of susceptible bacteria during antibiotic treatment.
- Persistence is linked to bacterial heterogeneity and can promote the evolution of antibiotic resistance.
- Novel methods for persister detection and eradication strategies are emerging.
Conclusions:
- Antibiotic persistence is a significant, underestimated factor in treatment failure and infection relapse.
- Targeting bacterial persistence is essential for developing effective therapies against recalcitrant infections.
- Further research into persistence mechanisms and novel therapeutic approaches is critical for combating AMR.
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