Neisseria gonorrhoeae

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Yueping Yin - One of the best experts on this subject based on the ideXlab platform.

Monica M Lahra - One of the best experts on this subject based on the ideXlab platform.

Yonatan H Grad - One of the best experts on this subject based on the ideXlab platform.

  • increased power from conditional bacterial genome wide association identifies macrolide resistance mutations in Neisseria gonorrhoeae
    Nature Communications, 2020
    Co-Authors: Kevin C, Yonatan H Grad, Tatum D Mortimer, Marissa A Duckett, Allison L Hicks, Nicole E Wheeler, Leonor Sanchezbuso
    Abstract:

    The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power. Here, we show that compared to single-locus GWAS, conducting GWAS conditioned on known resistance mutations reduces the number of false positives and identifies a G70D mutation in the RplD 50S ribosomal protein L4 as significantly associated with increased azithromycin resistance (p-value = 1.08 × 10−11). We experimentally confirm our GWAS results and demonstrate that RplD G70D and other macrolide binding site mutations are prevalent (present in 5.42% of 4850 isolates) and widespread (identified in 21/65 countries across two decades). Overall, our findings demonstrate the utility of conditional associations for improving the performance of microbial GWAS and advance our understanding of the genetic basis of macrolide resistance. The mechanisms underlying resistance of Neisseria gonorrhoeae to the antibiotic azithromycin are incompletely understood. Here, Ma et al. conduct a conditional genome-wide association study to identify new resistance mutations and experimentally confirm that a mutation in ribosomal protein L4 confers increased resistance.

  • azithromycin susceptibility among Neisseria gonorrhoeae isolates and seasonal macrolide use
    The Journal of Infectious Diseases, 2019
    Co-Authors: Scott W Olesen, Elizabeth Torrone, John R Papp, Robert D Kirkcaldy, Marc Lipsitch, Yonatan H Grad
    Abstract:

    Rising azithromycin nonsusceptibility among Neisseria gonorrhoeae isolates threatens current treatment recommendations, but the cause of this rise is not well understood. We performed an ecological study of seasonal patterns in macrolide use and azithromycin resistance in N. gonorrhoeae, finding that population-wide macrolide use is associated with increased azithromycin nonsusceptibility. These results, indicative of bystander selection, have implications for antibiotic prescribing guidelines.

  • in vitro selection of Neisseria gonorrhoeae mutants with elevated mic values and increased resistance to cephalosporins
    Antimicrobial Agents and Chemotherapy, 2014
    Co-Authors: Stevenr Johnson, Marc Lipsitch, Yonatan H Grad, Satishkumar Ranganathan Ganakammal, Mark Burroughs, Mike Frace, Ryan Weil, David L Trees
    Abstract:

    Strains of Neisseria gonorrhoeae with mosaic penA genes bearing novel point mutations in penA have been isolated from ceftriaxone treatment failures. Such isolates exhibit significantly higher MIC values to third-generation cephalosporins. Here we report the in vitro isolation of two mutants with elevated MICs to cephalosporins. The first possesses a point mutation in the transpeptidase region of the mosaic penA gene, and the second contains an insertion mutation in pilQ.

Shaochun Chen - One of the best experts on this subject based on the ideXlab platform.

Magnus Unemo - One of the best experts on this subject based on the ideXlab platform.