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Identification of the molecular mechanism of trimethoprim resistance in Listeria monocytogenes

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cris.lastimport.scopus2024-02-12T19:33:17Z
dc.abstract.enTrimethoprim with sulfamethoxazole is a therapeutic agent combination used to treat infections caused by the facultative intracellular foodborne pathogen Listeria monocytogenes. The aim of this study was to assess the frequency of resistance of L. monocytogenes arising due to exposure to trimethoprim and subsequently investigate the molecular mechanisms of resistance. After exposure of a culture of L. monocytogenes ATCC 13932 to trimethoprim at 10-fold the minimal inhibitory concentration spontaneous resistant mutants were recovered, giving a frequency of resistance development of 6.85 ± 0.92 × 10-8. The isolates exhibited a 32-64-fold decrease in susceptibility compared with the parental strain. These results indicate the capacity of L. monocytogenes to develop low-level resistance toward trimethoprim after exposure to the drug. The trimethoprim resistance genes (dhfr) and their promoter regions from all trimethoprim-resistant isolates were amplified and sequenced, leading to the identification of four single amino acid substitutions (Met20-Val, Pro21-Leu, Thr46-Asn, Val95-Leu) and two double substitutions (Met20-Ile+Thr46-Asn and Thr46-Asn+Leu85-Phe) in DHFR. Of the identified mutations, the Thr46-Asn substitution has not been previously reported as the mechanism of resistance to trimethoprim in other bacteria; thus this substitution seems to be unique to L. monocytogenes. The expression of the mutated L. monocytogenes dhfr genes in Escherichia coli led to decreased susceptibility of the heterological host, therefore proving that the identified point mutations in dhfr serve as the molecular mechanism of acquired resistance of L. monocytogenes to trimethoprim.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKorsak, Dorota
dc.contributor.authorKrawczyk-Balska, Agata
dc.date.accessioned2024-01-25T03:43:37Z
dc.date.available2024-01-25T03:43:37Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.identifier.doi10.1089/FPD.2017.2323
dc.identifier.issn1535-3141
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/108884
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofFoodborne Pathogens and Disease
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enL. monocytogenes
dc.subject.endhfr gene mutations
dc.subject.endihydrofolate reductase (DHFR)
dc.subject.entrimethoprim
dc.titleIdentification of the molecular mechanism of trimethoprim resistance in Listeria monocytogenes
dc.typeJournalArticle
dspace.entity.typePublication