Molecular mechanisms behind Beta-Lactam resistance: A review | ||||
| Microbes and Infectious Diseases | ||||
| Articles in Press, Accepted Manuscript, Available Online from 28 August 2025 | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/mid.2025.381379.2753 | ||||
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| Authors | ||||
Alisha Sinha1; Ishwar Chandra Behera2; Mahesh Chandra Sahu   3
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| 1Centre for Biotechnology, Siksha ‘O’ Anusandhan Deemed to be University, Kalinganagar, Bhubaneswar-751003, Oisha, India | ||||
| 2Department of Neuro-Science ICU, IMS and SUM Hospital, Kalinga Nagar, Bhubaneswar-751003, Odisha, India | ||||
| 3Division of Microbiology, ICMR-Regional Medical Research Centre, Chandrasekharpur, Bhubaneswar-751023, Odisha, India. | ||||
| Abstract | ||||
| Background: Beta-lactam antibiotics have been pivotal in combating bacterial infections due to their ability to disrupt cell wall synthesis, leading to bacterial lysis. Since the advent of penicillin, these drugs have dramatically reduced morbidity and mortality. However, the escalating incidence of beta-lactam resistance presents a major global health challenge, undermining the efficacy of first-line therapies. This resistance primarily arises from three key mechanisms: enzymatic degradation by beta-lactamases, structural alterations in penicillin-binding proteins (PBPs) reducing drug affinity, and decreased membrane permeability that limits antibiotic entry. These mechanisms may function independently or synergistically, contributing to varying resistance levels and complicating clinical management. This review explores the molecular basis of beta-lactam resistance, its clinical implications, the evolution of resistance patterns, and current diagnostic and therapeutic challenges. Emerging strategies aimed at overcoming resistance are also discussed. A comprehensive understanding of these mechanisms is crucial for guiding future antibiotic development and implementing effective public health interventions. | ||||
| Keywords | ||||
| Beta-lactam resistance; Beta-lactamase enzymes; Penicillin-binding proteins (PBPs); Antibiotic resistance mechanisms; Bacterial membrane permeability | ||||
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