The Role of Proteomics in Bacterial Response to Antibiotics

Abstract

For many years, we have tried to use antibiotics to eliminate the persistence of pathogenic bacteria. However, these infectious agents can recover from antibiotic challenges through various mechanisms, including drug resistance and antibiotic tolerance, and continue to pose a global threat to human health. To design more efficient treatments against bacterial infections, detailed knowledge about the bacterial response to the commonly used antibiotics is required. Proteomics is a well-suited and powerful tool to study molecular response to antimicrobial compounds. Bacterial response profiling from system-level investigations could increase our understanding of bacterial adaptation, the mechanisms behind antibiotic resistance and tolerance development. In this review, we aim to provide an overview of bacterial response to the most common antibiotics with a focus on the identification of dynamic proteome responses, and through published studies, to elucidate the formation mechanism of resistant and tolerant bacterial phenotypes.

Keywords: antibiotic resistance; antibiotic tolerance; antibiotics; multi-drug resistant bacteria; pathogens; proteomics.

Figure 1

Overview of the common antibiotic resistance mechanism in bacteria. Molecular mechanisms of antibiotic resistance that includes target modification, drug inactivation, decreased affinity to lipopolysaccharides (LPS) and penicillin binding protein (PBP), and expression of porins and efflux pumps are shown.

Figure 2

Chemical structure of conserved ring structure in β-lactam antibiotics and side-chain functionalities (R₁ and R₂) of three β-lactam antibiotics, ampicillin, oxacillin, and meropenem. Dashed lines represent the connecting bonds to the β-lactam ring (red).

Figure 3

The chemical structures of three aminoglycoside compound. r tobramycin, kanamycin, and gentamicin are shown. All three compounds chare similar ring number 1 indicated across the structures.

Figure 4

The chemical structure of two antibiotics, azithromycin, and erythromycin that belong to the macrolide class are shown. Conserved ring structures of sugars 1 and 2 (red) and varied lactone ring are shown.

Figure 5

Chemical structures of three clinically used quinolone antibiotics is shown.

Figure 6

Chemical structures of cyclic lipopeptides, polymyxin (B₁ and B₂), colistin (A and B), and daptomycin, are shown. R=CH₃ is polymyxin B1 and R=H is polymyxin B2. Similarly, for colistin, R=CH₃ is colistin A and R=H is colistin B. The ring in daptomycin consist of 10 varied amino acids and the tail contains different amino acid composition along with longer carbon chain (10 carbons).