Fluoroquinolone resistance-associated determinants in ciprofloxacin-susceptible Shigella isolates from Senegal

Abstract

Introduction Fluoroquinolones remain important therapeutic options for shigellosis, but the accumulation of chromosomal and plasmid-mediated resistance determinants threatens their continued effectiveness. Genomic data on fluoroquinolone resistance-associated determinants in Shigella from West Africa remain limited. Here, we investigated the epidemiological, phenotypic, and genomic characteristics of clinical Shigella isolates recovered through Senegal’s national sentinel surveillance system between 2020 and 2021, with particular emphasis on fluoroquinolone resistance-associated genomic determinants. Methods Stool specimens collected from patients with acute diarrhea were cultured for Shigella, followed by antimicrobial susceptibility testing and whole-genome sequencing. Genomes were analyzed for antimicrobial resistance determinants, quinolone resistance-determining region (QRDR) mutations, plasmid replicons, virulence-associated genes, sequence types, and core-genome phylogenetic relationships. Results Among 900 diarrheal stool specimens, 22 Shigella isolates were recovered, including 12 S. flexneri, 7 S. sonnei, and 3 S. boydii. All isolates were phenotypically susceptible to ciprofloxacin, whereas qnrS1 was detected in 9/22 isolates (40.9%) and the QRDR substitution gyrA S83L in 4/22 (18.2%). These determinants occurred in non-overlapping isolates, and no gyrA S83V or parC QRDR mutation was detected. IncFII replicons were identified in all isolates, while additional replicons showed heterogeneous distributions across species and sequence types. The fluoroquinolone resistance-associated determinants were distributed across distinct genetic backgrounds rather than being restricted to a single lineage. Conclusion These findings demonstrate that phenotypic susceptibility to ciprofloxacin may coexist with fluoroquinolone resistance-associated genomic determinants in clinical Shigella isolates. Integrating WGS with routine antimicrobial susceptibility testing may strengthen surveillance of emerging fluoroquinolone resistance in Shigella in Senegal and West Africa.