Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci.

Autor: Kojic M; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia. Electronic address: mkojic@imgge.bg.ac.rs., Jovcic B; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia; Faculty of Biology, University of Belgrade, Belgrade, Serbia., Miljkovic M; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia., Novovic K; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia., Begovic J; Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia., Studholme DJ; Biosciences, College of Life and Environmental Sciences, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK.
Jazyk: angličtina
Zdroj: Microbiological research [Microbiol Res] 2020 Dec; Vol. 241, pp. 126583. Date of Electronic Publication: 2020 Aug 24.
DOI: 10.1016/j.micres.2020.126583
Abstrakt: Bacteria can gain resistance to antimicrobials by acquiring and expressing genetic elements that encode resistance determinants such as efflux pumps and drug-modifying enzymes, thus hampering treatment of infection. Previously we showed that acquisition of spectinomycin resistance in a lactococcal strain was correlated with a reversible genomic inversion, but the precise location and the genes affected were unknown. Here we use long-read whole-genome sequencing to precisely define the genomic inversion and we use quantitative PCR to identify associated changes in gene expression levels. The boundaries of the inversion fall within two identical copies of a prophage-like sequence, located on the left and right replichores; this suggests possible mechanisms for inversion through homologous recombination or prophage activity. The inversion is asymmetrical in respect of the axis between the origin and terminus of the replication and modulates the expression of a SAM-dependent methyltransferase, whose heterologous expression confers resistance to spectinomycin in lactococci and that is up-regulated on exposure to spectinomycin. This study provides one of the first examples of phase variation via large-scale chromosomal inversions that confers a switch in antimicrobial resistance in bacteria and the first outside of Staphylococcus aureus.
(Crown Copyright © 2020. Published by Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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