Comparative genomic and phenotypic analysis of invasive non-typhoidal Salmonella isolates from Siaya, Kenya

Multidrug-resistant (MDR) bacteria pose a major challenge to the clinical management of infections especially in resource-poor settings. Although non-typhoidal Salmonella (NTS) generally cause a self-limiting gastroenteritis... [ view full abstract ]

Multidrug-resistant (MDR) bacteria pose a major challenge to the clinical management of infections especially in resource-poor settings. Although non-typhoidal Salmonella (NTS) generally cause a self-limiting gastroenteritis in USA, invasive NTS has emerged in sub-Saharan Africa as a major cause of bacteremia, a life-threatening bloodstream infection in humans. Here, we sequenced and characterized nine Salmonella enterica serotype Typhimurium isolates and two Salmonella enterica serotype Enteritidis isolates obtained from pediatric bacteremia patients who initially failed to respond to antibiotic treatment at a referral hospital in Siaya, Kenya from 2003-2009.  All nine S. Typhimurium isolates formed a single clade within S. Typhimurium D23580. One of S. Typhimurium isolates, a ceftriaxone-susceptible strain UGA14 has been finished and identified to have 4 plasmids: two larger plasmids similar to pKST313 and pSLT-BT harboring MDR genes and two novel SCP (small cryptic plasmid) possessing site-specific recombination properties.  The comparative study revealed the main difference between UGA14 and other eight S. Typhimurium is the different MDR gene island harbored on virulence-associated plasmids, which can explain the variation of antimicrobial susceptibility based on ESBL testing.  We further compared two S. Typhimurium strains (UGA14 &10) with Salmonella Typhimurium type-strain ATCC 13311 using Biolog phenotypic arrays over 1920 distinct growth conditions.  Some good correlations between genotype and phenotype can be explained by its genetic variation, including emergent plasmids, pseudogene formation, SNP, segmental duplication and INDELs.  All our study support the idea that epidemic S. Typhimurium isolates have undergone microevolution and clonal replacement in the field.