Circulating Genotypes of Salmonella Typhi and Their Relationship With Quinolone Resistance in Northern Brazil

Quinolone resistance in Salmonella Typhi, the causative agent of typhoid fever, represents a significant and growing global public health concern, severely limiting treatment options, especially in regions with a high disease burden. The recurrent emergence of resistant isolates underscores the need for studies investigating genetic characteristics and mechanisms that allow the characterization of circulating lineages and their association with specific antimicrobial resistance mechanisms. This study aimed to identify circulating S. Typhi genotypes and their relationship with quinolone susceptibility in Northern Brazil. Six S. Typhi isolates from sporadic cases in Pará State, Northern Brazil, collected between 2010 and 2022 and presenting different antimicrobial susceptibility profiles, were analyzed from the bacterial collection of the Bacteriology Section, Instituto Evandro Chagas (SABAC-IEC). The isolates were subjected to disk diffusion assays to assess susceptibility to nalidixic acid, pefloxacin, and ciprofloxacin, and to broth microdilution testing for ciprofloxacin evaluation. Genomic DNA was extracted, and whole-genome sequencing (WGS) was performed to determine genotypes and detect antimicrobial resistance determinants. Genotyping followed the GenoTyphi scheme on the PathogenWatch platform. MLST profiles were determined using MLST v2. 0, and resistance genes were identified with ResFinder v4. 4. 3. Genotype 2. 0. 2 (sequence type ST2) predominated in the region, corresponding to 5 of the 6 isolates, while 1 isolate was identified as genotype 3 (ST1). Isolates belonging to genotype 2. 0. 2 were susceptible to quinolones, whereas the genotype 3 isolate harbored the gyrAD87G mutation and exhibited resistance to nalidixic acid, ciprofloxacin (MIC 16 µg/mL), and pefloxacin. No mutations were detected in gyrB, parC, or parE. These preliminary findings revealed the circulation of two distinct S. Typhi lineages in Pará State. Genotype 3 appears to represent a high-risk lineage in the region, as it was associated with quinolone resistance and potential therapeutic failure, posing a significant public health challenge.