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Publication Abstract from PubMed

Nocardia are Gram-positive bacteria from the Actinobacteria phylum. Some Nocardia species can infect humans and are usually considered to be opportunist pathogens, as they often infect immunocompromised patients. Although their clinical incidence is low, many Nocardia species are now considered to be emerging pathogens. Primary sites of infection by Nocardia are the skin or the lungs, but dissemination to other body parts is very frequent. These disseminated infections are very difficult to treat and thus are tackled with multiple classes of antibiotics, in addition to the traditional treatment targeting the folate pathway. beta-Lactams are often included in the regimen, but many Nocardia species present moderate or strong resistance to some members of this drug class. Genomic, microbiological and biochemical studies have reported the presence of class A beta-lactamases (ABLs) in a handful of Nocardia species, but no structural investigation of Nocardia beta-lactamases has yet been performed. In this study, the expression, purification and preliminary biochemical characterization of an ABL from an N. cyriacigeorgica (NCY-1) clinical strain are reported. The crystallization and the very high resolution crystal structure of NCY-1 are also described. The sequence and structural analysis of the protein demonstrate that NCY-1 belongs to the class A1 beta-lactamases and show its very high conservation with ABLs from other human-pathogenic Nocardia. In addition, the presence of one molecule of citrate tightly bound in the catalytic site of the enzyme is described. This structure may provide a solid basis for future drug development to specifically target Nocardia spp. beta-lactamases.

Biochemical and structural characterization of a class A beta-lactamase from Nocardia cyriacigeorgica.,Feuillard J, Couston J, Benito Y, Hodille E, Dumitrescu O, Blaise M Acta Crystallogr F Struct Biol Commun. 2024 Jan 1;80(Pt 1):13-21. doi: , 10.1107/S2053230X23010671. Epub 2024 Jan 1. PMID:38168018^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.