Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro

Antimicrobial Agents and Chemotherapy
Zijian GongXiaoyuan Xie

Abstract

The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated Pi...Continue Reading

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Citations

Oct 30, 2016·Expert Review of Molecular Diagnostics·Teresa CimminoJean-Marc Rolain
Sep 13, 2017·Antimicrobial Agents and Chemotherapy·Anna KnöppelDan I Andersson
Sep 8, 2016·Antimicrobial Agents and Chemotherapy·Claire de CurraizeBéatrice Bercot
Jun 6, 2020·Expert Review of Molecular Diagnostics·Charlotte A Gaydos, Johan H Melendez
Jul 24, 2020·Genome Biology·Gerry Tonkin-HillJulian Parkhill
Aug 29, 2017·Tropical Medicine and Infectious Disease·Clark Martin P AranetaRaziel C Gayoba
Mar 25, 2021·The Journal of Antimicrobial Chemotherapy·J G E LaumenC Kenyon
Aug 1, 2021·Pharmacology Research & Perspectives·Ashagrachew TewabeGebremariam Birhanu
Dec 8, 2021·Expert Review of Molecular Diagnostics·Daniel Golparian, Magnus Unemo

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