Agarwal Vidhu, Yadav Tara Chand, Tiwari Akhilesh, Varadwaj Pritish
Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, Jhalwa, Uttar Pradesh, India.
Department of Biotechnology, Indian Institute of Technology, Roorkee, Uttarakhand, India.
J Biomol Struct Dyn. 2023 Mar;41(5):2046-2073. doi: 10.1080/07391102.2021.2023645. Epub 2022 Jan 6.
An increasing global health challenge is antimicrobial resistance. Bacterial infections are often treated by using β-lactam antibiotics. But several resistance mechanisms have evolved in clinically mutated bacteria, which results in resistance against such antibiotics. Among which production of novel β-lactamase is the major one. This results in bacterial resistance against penicillin, cephalosporin, and carbapenems, which are considered to be the last resort of antibacterial treatment. Hence, β-lactamase enzymes produced by such bacteria are called extended-spectrum β-lactamase and carbapenemase enzymes. Further, these bacteria have developed resistance against many β-lactamase inhibitors as well. So, investigation of important residues that play an important role in altering and expanding the spectrum activity of these β-lactamase enzymes becomes necessary. This review aims to gather knowledge about the role of residues and their mutations in class A β-lactamase, which could be responsible for β-lactamase mediated resistance. Class A β-lactamase enzymes contain most of the clinically significant and expanded spectrum of β-lactamase enzymes. Ser70, Lys73, Ser130, Glu166, and Asn170 residues are mostly conserved and have a role in the enzyme's catalytic activity. In-depth investigation of 69, 130, 131, 132, 164, 165, 166, 170, 171, 173, 176, 178, 179, 182, 237, 244, 275 and 276 residues were done along with its kinetic analysis for knowing its significance. Further, detailed information from many previous studies was gathered to know the effect of mutations on the kinetic activity of class A β-lactamase enzymes with β-lactam antibiotics.Communicated by Ramaswamy H. Sarma.
日益严峻的全球健康挑战是抗菌药物耐药性。细菌感染通常使用β-内酰胺类抗生素进行治疗。但临床突变细菌已进化出多种耐药机制，从而导致对这类抗生素产生耐药性。其中，新型β-内酰胺酶的产生是主要原因。这导致细菌对青霉素、头孢菌素和碳青霉烯类抗生素产生耐药性，而这些抗生素被认为是抗菌治疗的最后手段。因此，此类细菌产生的β-内酰胺酶被称为超广谱β-内酰胺酶和碳青霉烯酶。此外，这些细菌还对许多β-内酰胺酶抑制剂产生了耐药性。所以，研究在改变和扩展这些β-内酰胺酶的光谱活性中起重要作用的关键残基变得很有必要。本综述旨在收集有关A类β-内酰胺酶中残基及其突变作用的知识，这些残基可能导致β-内酰胺酶介导的耐药性。A类β-内酰胺酶包含了大多数具有临床意义且光谱扩展的β-内酰胺酶。Ser70、Lys73、Ser130、Glu166和Asn170残基大多保守，且在酶的催化活性中起作用。对69、130、131、132、164、165、166、170、171、173、176、178、179、182、237、244、275和276残基进行了深入研究，并对其进行动力学分析以了解其重要性。此外，还收集了许多先前研究的详细信息，以了解突变对A类β-内酰胺酶与β-内酰胺类抗生素的动力学活性的影响。由拉马斯瓦米·H·萨尔马传达。
