Genomic and phenotypic characterization of plasmid-mediated extensively drug-resistant Salmonella Typhi from Lahore Pakistan carrying IncY IncQ1 and IncC replicons

Abstract Antimicrobial resistance and emergence of MDR and XDR Salmonella enterica subsp. enterica serovar Typhi is a major threat in Pakistan. Failure of treatment with conventional antibiotics leads to importance of exploring alternative treatment plan. Therefore, this study aimed to check the resistance patterns and delineate the molecular basis of resistance among clinical isolates of S. typhi. 384 clinical isolates of S. Typhi were processed according to standard microbiological techniques. Antimicrobial sensitivity testing was performed by using VITEK-2 compact system. DNA was extracted and Gene specific PCR was done to confirm XDR S. Typhi. Whole Genome Sequencing was performed and Plasmidfinder software was used for plasmids identification. Among 382 S. Typhi, males were predominant which accounted for 61.7% and 43.2% samples were from age group of less than 10 years. Carbapenems and azithromycin showed 100% sensitivity. XDR S. Typhi accounted for 38% of total isolates. Most commonly found plasmids were IncQ1, IncY and IncC. Whole genome assemblies generated using SPAdes v3.15.5 achieved a mean coverage depth of ~ 125 × , revealing the principal plasmid replicons IncQ1, IncY, IncC, and IncA/C2 associated with multidrug resistance in Salmonella Typhi. XDR Salmonella Typhi poses a significant challenge in the treatment of typhoid fever and serious threat for public health. Horizontal transfer of plasmids among Enterobacterales contributes to the emergence and maintenance of XDR S. Typhi.