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In vitro evolution of ciprofloxacin resistance in Neisseria commensals and derived mutation population dynamics in natural Neisseria populations.
FEMS Microbiol Lett
January 2025
Rochester Institute of Technology, Thomas H. Gosnell School of Life Sciences, Rochester, NY, USA.
Commensal Neisseria are members of a healthy human oropharyngeal microbiome; however, they also serve as a reservoir of antimicrobial resistance for their pathogenic relatives. Despite their known importance as sources of novel genetic variation for pathogens, we still do not understand the full suite of resistance mutations commensal species can harbor. Here, we use in vitro selection to assess the mutations that emerge in response to ciprofloxacin selection in commensal Neisseria by passaging 4 replicates of 4 different species in the presence of a selective antibiotic gradient for 20 days; then categorized derived mutations with whole genome sequencing.
View Article and Find Full Text PDFEmergence of ceftriaxone-resistant Neisseria gonorrhoeae through horizontal gene transfer among Neisseria spp.
J Infect Dis
January 2025
Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
Objectives: It has been suggested that the emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae involves the incorporation of the penA gene from commensal Neisseria spp. that are resistant to ceftriaxone. However, the mechanism of this mosaic penA generation is unknown.
View Article and Find Full Text PDFHigh Prevalence of Sexually Transmitted Infections and Poor Sensitivity and Specificity of Screening Algorithms for Chlamydia and Gonorrhea Among Female Sex Workers in Zimbabwe: Analysis of Respondent-Driven Sampling Surveys in 3 Communities.
Sex Transm Dis
February 2025
Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Background: Effective strategies to reduce sexually transmitted infection burden and transmission among female sex workers (FSWs) and their networks are needed. We report sexually transmitted infection prevalence among FSWs in Zimbabwe and investigate the performance of screening algorithms.
Methods: Respondent-driven sampling (RDS) surveys, including blood sampling for syphilis serology, were conducted among FSWs in 3 communities in Zimbabwe in 2017.
A new class of penicillin-binding protein inhibitors to address drug-resistant .
bioRxiv
December 2024
Venatorx Pharmaceuticals, Inc., Malvern, PA, USA.
β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.
View Article and Find Full Text PDFDifferential contribution of PBP occupancy and efflux on the effectiveness of β-lactams at their target site in clinical isolates of Neisseria gonorrhoeae.
PLoS Pathog
December 2024
Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Neisseria gonorrhoeae exhibits alarming antibiotic resistance trends and poses a significant challenge in therapeutic management. This study aimed to explore the association of penA alleles with penicillin-binding protein (PBP) occupancy patterns and reduced outer membrane permeability, impacting susceptibility to last-line cephalosporins and potential β-lactam candidates. The whole genome sequence, the MICs and PBP IC50s were determined for 12 β-lactams and β-lactamase inhibitors in 8 clinical isolates with varying β-lactam sensitivity, 2 ATCC, and 3 WHO cephalosporin-resistant reference strains.
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