Multidrug-resistant monophasic Salmonella Typhimurium ST34 strain producing blaNDM-5 carbapenemase isolated from a patient with rectal cancer in Hainan, China: comprehensive whole genome dissection of antibiotic resistance and virulence determinants

Abstract

Here, we report the identification and comprehensive whole-genome characterization of a New Delhi metallo-β-lactamase 5 ( bla NDM-5 )-producing multidrug-resistant (MDR) monophasic Salmonella Typhimurium ST34 strain SYA001 from an immunocompromised rectal cancer patient. Monophasic Salmonella Typhimurium ( Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:-) is one of the leading causative agents of foodborne gastroenteritis and hospitalization worldwide, and the rapid emergence and spread of carbapenem-resistant strains have severely compromised clinical treatment and posed a major threat to public health. In this study, a series of standardized phenotypic assays were performed to characterize the microbiological, biochemical, and antimicrobial resistance profiles of strain SYA001. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), biochemical identification, and slide agglutination serotyping were used for species and serotype confirmation. Antimicrobial susceptibility testing was conducted using the VITEK 2 compact system, and six types of carbapenemases were screened via a colloidal gold immunochromatographic assay. Whole-genome sequencing (WGS) was performed on the DNBSEQ-T7 platform, and a comprehensive bioinformatics pipeline was applied to dissect the genomic structure, phylogenetic characteristics, antibiotic resistance determinants, plasmid profiles, prophage regions, Salmonella pathogenicity islands (SPIs), and protein-protein interaction (PPI) network of the strain. Our results confirmed that SYA001 is a serovar 1,4,[5],12:i:- monophasic Salmonella Typhimurium belonging to the globally epidemic ST34 clone. The strain exhibited an MDR phenotype, with resistance to 7 classes of antibiotics including carbapenems, cephalosporins, and aminoglycosides, and was only susceptible to aztreonam, amikacin, tigecycline, and colistin. Genomic analysis identified the core carbapenem resistance gene bla NDM-5 , along with multiple coexisting resistance genes including bla OXA-10 , qnrS 1, tet (A), sul 2, and sul 3 and so on. Four plasmid replicons (IncHI2, IncHI2A, IncQ1, p0111), 15 prophage regions, and a complete set of virulence-related SPIs (SPI-1 to SPI-5,SPI-9, SPI-13, SPI-14) were detected. PPI network analysis revealed AcrA as the core hub of the efflux-mediated resistance regulatory network. This study provides genomic insights into bla NDM-5 -producing MDR monophasic Salmonella. Typhimurium from an immunocompromised rectal cancer patient, supplements clinical surveillance data of carbapenem-resistant Salmonella in Hainan.