Proteomic interrogation of antibiotic resistance and persistence in Escherichia coli – progress and potential for medical research

ABSTRACT

Introduction

Escherichia coli

strains possess two survival strategies to endure lethal antibiotic exposure including antibiotic resistance and persistence, in which persistence can contribute to the emergence of antibiotic resistance and increasing the risk of multidrug resistance. Using high-throughput proteomics for the comprehensive understanding of mechanisms of antibiotic resistance and persistence is an effective strategy for development of target-based anti-bacterial therapies.

Areas covered

In this review, we summarize a comprehensive proteomic perspective of antibiotic resistance and persistence in E.coli, and overview of anti-antibiotic resistance and anti-persister molecules and strategies for the development of potential therapies.

Expert opinion

Proteomics allows us to globally identify the critical proteins and pathways involved in antibiotic resistance and persistence. Advancements in methodologies of proteomics and multi-omic strategies are required to overcome the limitations of proteomics and better understand mechanisms of antibiotic resistance and persistence in E.coli, and to open the possibility for identification of new targets for alternative strategies in therapeutics.

KEYWORDS:

• Escherichia coli
• proteomics
• antibiotic resistance

Article highlights

• Pathogenic and multidrug resistant E.coli can cause life-threatening infections. Proteomics could be used to monitor dynamic events globally in resistance development and provide a more comprehensive view of molecular mechanisms of antibiotic resistance in E.coli than non-omic strategies.

• Targets based on the mechanisms of antibiotic resistance in E.coli do contribute to the development of alternatively therapeutic strategies to control the morbidity and mortality associated with antibiotic resistance infections.

• Proteomics is the best option to investigate the mechanisms of antibiotic tolerance and reveals the key proteins playing important role in this phenotype, but many factors prevent the utilization of proteomics in persistence studies. Recently, efficient approaches have been developed to satisfy the acquirement for proteomics technology.

• Mechanisms of persister formation are helpful for the development of target based anti-persister molecules in E.coli.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer declarations

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the 2019 Fujian Provincial Science and Technology Commissioner Project, grant number: SKTP2014; the Excellent Talents Project of Minnan Normal University of New Century, grant number: MX13004; the Key Project of Fujian University of Youth Natural Foundation, grant number: JZ160454; the Project of Fujian Natural Science Foundation of China, grant number: 2017J01453; and the Fujian Provincial Department of Science and Technology, grant number: 2019N0018.