TY  - JOUR
AU  - Kojić, Milan
AU  - Jovčić, Branko
AU  - Miljković, Marija
AU  - Novović, Katarina
AU  - Begović, Jelena
AU  - Studholme, David J.
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1373
AB  - 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.
PB  - Elsevier Gmbh, Munich
T2  - Microbiological Research
T1  - Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci
VL  - 241
DO  - 10.1016/j.micres.2020.126583
ER  - 

@article{
author = "Kojić, Milan and Jovčić, Branko and Miljković, Marija and Novović, Katarina and Begović, Jelena and Studholme, David J.",
year = "2020",
abstract = "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.",
publisher = "Elsevier Gmbh, Munich",
journal = "Microbiological Research",
title = "Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci",
volume = "241",
doi = "10.1016/j.micres.2020.126583"
}

Kojić, M., Jovčić, B., Miljković, M., Novović, K., Begović, J.,& Studholme, D. J.. (2020). Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci. in Microbiological Research
Elsevier Gmbh, Munich., 241.
https://doi.org/10.1016/j.micres.2020.126583

Kojić M, Jovčić B, Miljković M, Novović K, Begović J, Studholme DJ. Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci. in Microbiological Research. 2020;241.
doi:10.1016/j.micres.2020.126583 .

Kojić, Milan, Jovčić, Branko, Miljković, Marija, Novović, Katarina, Begović, Jelena, Studholme, David J., "Large-scale chromosome flip-flop reversible inversion mediates phenotypic switching of expression of antibiotic resistance in lactococci" in Microbiological Research, 241 (2020),
https://doi.org/10.1016/j.micres.2020.126583 . .