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Review
. 2022 Sep 23:13:952633.
doi: 10.3389/fmicb.2022.952633. eCollection 2022.

Breaking down the cell wall: Still an attractive antibacterial strategy

Jingxuan Zhou  1   2   3 , Yi Cai  2   3 , Ying Liu  2   3 , Haoyue An  2   3 , Kaihong Deng  2   3 , Muhammad Awais Ashraf  4 , Lili Zou  2   3 , Jun Wang  1
Affiliations
Review

Breaking down the cell wall: Still an attractive antibacterial strategy

Jingxuan Zhou et al. Front Microbiol. .

Abstract

Since the advent of penicillin, humans have known about and explored the phenomenon of bacterial inhibition via antibiotics. However, with changes in the global environment and the abuse of antibiotics, resistance mechanisms have been selected in bacteria, presenting huge threats and challenges to the global medical and health system. Thus, the study and development of new antimicrobials is of unprecedented urgency and difficulty. Bacteria surround themselves with a cell wall to maintain cell rigidity and protect against environmental insults. Humans have taken advantage of antibiotics to target the bacterial cell wall, yielding some of the most widely used antibiotics to date. The cell wall is essential for bacterial growth and virulence but is absent from humans, remaining a high-priority target for antibiotic screening throughout the antibiotic era. Here, we review the extensively studied targets, i.e., MurA, MurB, MurC, MurD, MurE, MurF, Alr, Ddl, MurI, MurG, lipid A, and BamA in the cell wall, starting from the very beginning to the latest developments to elucidate antimicrobial screening. Furthermore, recent advances, including MraY and MsbA in peptidoglycan and lipopolysaccharide, and tagO, LtaS, LspA, Lgt, Lnt, Tol-Pal, MntC, and OspA in teichoic acid and lipoprotein, have also been profoundly discussed. The review further highlights that the application of new methods such as macromolecular labeling, compound libraries construction, and structure-based drug design will inspire researchers to screen ideal antibiotics.

Keywords: antimicrobials; lipopolysaccharide; lipoprotein; peptidoglycan; teichoic acid.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Peptidoglycan biosynthesis pathway. UDP-GlcNAc, uridine diphosphate N-acetylglucosamine; PEP, phosphoenol pyruvate; MurA, UDP-GlcNAc enol pyruvate transferase; MurB, UDP-N-acetyl allylacetone glucosamine reductase; MurG, decadecenyl diphosphate-MurNAc-pentapeptide-UDP-GlcNAcGlcNAc transferase; MraY, UDP-MurNAc-pentapeptide phosphotransferase; PBP, penicillin-binding proteins.
Figure 2
Figure 2
Potential inhibitors target peptidoglycan. UDP-GlcNAc, uridine diphosphate N-acetylglucosamine; PEP, phosphoenol pyruvate; MurA, UDP-GlcNAc enol pyruvate transferase; MurB, UDP-N-acetyl allylacetone glucosamine reductase; MurG, decadecenyl diphosphate-MurNAc-pentapeptide- UDP-GlcNAcGlcNAc transferase; MraY, UDP-MurNAc-pentapeptide phosphotransferase; PBP, penicillin-binding proteins.
Figure 3
Figure 3
Potential inhibitors target lipopolysaccharide. BamA, the central component of the BamABCDE complex, it catalyzes both folding and insertion of nascent porins; MsbA, belongs to the ABC transporter superfamily, which reversely transports LPS from the intima leaflet synthesis site to the intima outer leaflet.
Figure 4
Figure 4
Potential inhibitors target teichoic acid. WTA, wall teichoic acid; LTA, lipoteichoic acid.
See this image and copyright information in PMC

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