Structural Insights for β-Lactam Antibiotics

Abstract

Antibiotic resistance has emerged as a global threat to modern healthcare systems and has nullified many commonly used antibiotics. β-Lactam antibiotics are among the most successful and occupy approximately two-thirds of the prescription antibiotic market. They inhibit the synthesis of the peptidoglycan layer in the bacterial cell wall by mimicking the D -Ala- D -Ala in the pentapeptide crosslinking neighboring glycan chains. To date, various β-lactam antibiotics have been developed to increase the spectrum of activity and evade drug resistance. This review emphasizes the three-dimensional structural characteristics of β-lactam antibiotics regarding the overall scaffold, working mechanism, chemical diversity, and hydrolysis mechanism by β-lactamases. The structural insight into various β-lactams will provide an in-depth understanding of the antibacterial efficacy and susceptibility to drug resistance in multidrug-resistant bacteria and help to develop better β-lactam antibiotics and inhibitors.

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“…However, challenges associated with poor pharmacokinetics, limited cellular uptake, and inefficient delivery to target tissues have constrained the translation of ASOs into successful therapies. Nevertheless, to date, nine ASO‐based drugs have secured regulatory approval for clinical use [16] . Other approaches include the use of engineered DNA‐binding proteins, such as zinc finger (ZF) proteins [17] and transcription activator‐like effector nucleases (TALENs) [18] .…”

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“…β-Lactam antibiotics refer to a large class of chemical structures with a β-lactam ring, including penicillins and cephalosporins most commonly used in clinics, as well as newly developed cephalosporins, thiomycetes and monocyclic antibiotics, which are atypical β-lactam antibiotics. 1,2 Such antibiotics have the advantages of strong bactericidal activity, 3 low toxicity, 4 wide indications 5 and good clinical efficacy. 6,7 β-Lactam drugs are widely used in clinical veterinary medicine 8 and animal husbandry in China.…”