Multidrug resistant invasive non-typhoidal Salmonella ST313 isolated in Brazil features unique pathogenic mechanisms

Abstract Invasive non-typhoidal Salmonella (iNTS) from the clonal type ST313 ( S . Typhimurium ST313) is the major cause of invasive salmonellosis disease in Africa. Recently in Brazil, iNTS ST313 strains have been isolated from different sources, but there is a lack of understanding the mechanisms behind how these gut bacteria are able to break the gut barrier and reach the patient’s bloodstream. Herein, we compared 13 S . Typhimurium ST313 strains genomes isolated from human-blood cultures investigating aspects of virulence and resistance mechanisms. RNAseq analyses were also performed between the clinical blood isolate and SL1344 prototype, which belongs to ST19 and it was originally isolated from human feces. That analysis reveals here 15-upregulated genes related to pathogenesis in S . Typhimurium ST313 compared to SL1344 (ST19) such as sopD2 , sifB, pipB , amongst others. We have also compared these clinical with non-clinical isolates from Brazil, a total of 22 genomes were studied by single nucleotide polymorphism (SNPs). The epidemiological analysis of 22 genomes of S . Typhimurium ST313 strains grouped them into three distinct clusters (A, B and C) by SNP analysis, where cluster A comprised five, the group B six, and the group C 11. The 13 clinical blood isolates were all resistant to streptomycin, 92. 3% strains were resistant to ampicillin and 15.39% strains were resistant to kanamycin. The resistance genes acrA , acrB , mdtK , emrB , emrR , mdsA and mdsB related to the production of efflux pumps were detected in all (100%) strains studied, similar to pathogenic traits investigated. In conclusion, we evidenced the S . Typhimurium ST313 strains isolated in Brazil are different of the African strains ST313. The elevated frequencies of virulence genes such as sseJ , sopD2 and pipB are a major concern in these Brazilian isolates, showing a higher pathogenic potential.