Bacterial Proteomics and Antibiotic Resistance Identification: Is Single-Cell Analysis a Worthwhile Pursuit?

Antibiotic resistance is a major threat to global public health. It is vital to understand the mechanism of antibiotic resistance development to prevent the emergence of new pan-resistant pathogenic bacteria and to develop new antibiotics. Measuring the differences in proteins among single bacterial cells can aid in identifying antibiotic resistance and antibiotic susceptibility due to their regulatory roles in bacterial physiology and homeostasis. Although single-cell proteomics has been successful in mammalian systems, attaining comparable performance in bacteria remains challenging due to the extremely limited proteome content of a single bacterial cell. This review discusses the role of proteomics analysis in determining antibiotic resistance and the various mass spectrometry-based strategies that have been successful in detecting protein biomarkers for antibiotic resistance from bulk proteomics analysis. It highlights the core challenges of bacterial single-cell proteomics in contrast to mammalian systems, explores emerging technologies, and the proteomes beyond the cells in studying antibiotic resistance development and antibiotic susceptibility testing.