Proteomics approach to understand bacterial antibiotic resistance strategies

ABSTRACT

Introduction: The understanding of novel antibiotic resistance mechanisms is essential to develop strategies against antibiotic-resistant pathogens, which has become an urgent task due to the worldwide emergence of antibiotic resistance.

Areas covered: In this review, the authors summarize the recent progress on antibiotic resistance caused by lab-evolved bacteria and clinical multidrug-resistant bacterial pathogens from the proteomics perspective.

Expert opinion: Proteomics provides a new platform for a comprehensive understanding of change in protein pathways that are engaged in antibiotics resistance, which is different from a genetic view that focuses on the role of an individual gene or protein. Further work is required to understand why and how the involved pathways are integrated for surviving antibiotic-mediated killing, to use other OMICs for better comprehension of antibiotic resistance mechanisms, and to develop reprogramming proteomics, which reverts an ‘antibiotic resistance proteome’ to an ‘antibiotic sensitive or antibiotic sensitive-like’ proteome, for the control of antibiotic-resistant pathogens.

KEYWORDS:

• Proteomics
• antibiotic resistance
• reprogramming proteomics

Article highlights

• It is estimated that the global death toll of antibiotic resistance will overtake that of cancer and exceed 10 million people per year by 2050. A proteomics-based approach expands our view of the bacterial strategy to resist antibiotics, thereby providing a viable way to understand antibiotic resistance mechanisms and manage the growing epidemic of antibiotic-resistant infections.

• Proteomics specifically addresses the global change in the abundance of proteins, altered pathways, and protein-protein interaction networks at the protein level. Thus, proteomics provides a more holistic perspective of the molecular mechanisms of antibiotic resistance than non-OMICs approaches.

• Most of the current proteomics data are derived from lab-evolved bacterial strains, which may not fully represent molecular changes found in clinically isolated multidrug-resistant strains. Further work on clinical isolates needs to be undertaken to delineate why and how protein pathways are integrated to survive antibiotic-mediated killing.

• Proteomics has advanced our knowledge of bacterial antibiotic resistance mechanisms, but other OMICs including genomics, transcriptomics, and metabolomics are functional complements to proteomics that reveal global changes at different layers in the bacterial cell. Therefore, these OMIC approaches need to be connected and applied together to comprehend antibiotic resistance.

• Reprogramming proteomics should be developed to revert an “antibiotic-resistance proteome” to an “antibiotic-sensitive or antibiotic-sensitive-like” proteome for the control of antibiotic-resistant pathogens.

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 disclosures

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

Additional information

Funding

This paper was sponsored by grants from the National Natural Science Foundation of China, grants: [U1701235, 31822058 31572654 and 31772888].