Whole-Genome Sequencing to Predict Antimicrobial Susceptibility Profiles in Neisseria gonorrhoeae. (3rd February 2023)

• Record Type: Journal Article
• Authors: Bristow, Claire C; Mortimer, Tatum D; Morris, Sheldon; Grad, Yonatan H; Soge, Olusegun O; Wakatake, Erika; Pascual, Rushlenne; Murphy, Sara McCurdy; Fryling, Kyra E; Adamson, Paul C; Dillon, Jo-Anne; Parmar, Nidhi R; Le, Hai Ha Long; Van Le, Hung; Ovalles Ureña, Reyna Margarita; Mitchev, Nireshni; Mlisana, Koleka; Wi, Teodora; Dickson, Samuel P; Klausner, Jeffrey D
• Is Part Of: Journal of infectious diseases. Volume 227:Number 7(2023)
• Page Start: 917
• Page End: 925
• Publication Date: 2023-02-03
• Subjects: Neisseria gonorrhoeae -- antimicrobial susceptibility testing -- whole-genome sequencing; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiad027
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. Methods: Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. Results: A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 μg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 μg/mL. Conclusions: Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials. Abstract : A single genetic marker, gyrA codon 91, correctly predicted ciprofloxacin susceptibility in a global collection of Neisseria gonorrhoeae isolates with genome sequences and phenotypic antimicrobial susceptibility data. For other antimicrobials, multiple molecular markers are needed to accurately predict antimicrobial susceptibility.