Non-typhoidal Salmonella (NTS) is a major global health concern that often causes bloodstream
infections in areas of the world affected by malnutrition and comorbidities such as HIV and
malaria. Developing a strategy to control the emergence and spread of highly invasive and
antimicrobial resistant NTS isolates requires a comprehensive analysis of epidemiological factors
and molecular pathogenesis. Here, we characterize 11 NTS isolates that caused bloodstream
infections in pediatric patients in Siaya, Kenya from 2003-2010. Nine isolates were identified as
S. Typhimurium sequence type 313 while the other two were S. Enteritidis. Comprehensive
genotypic and phenotypic analyses were performed to compare these isolates to those previously
identified in sub-Saharan Africa. We identified a S. Typhimurium isolate referred to as UGA14
that displayed novel plasmid, pseudogene and resistance features as compared to other isolates
reported from Africa. Notably, UGA14 is able to ferment both lactose and sucrose due to the
acquisition of insertion elements on the pKST313 plasmid. These findings show for the first time
the co-evolution of plasmid-mediated lactose and sucrose metabolism along with cephalosporin
resistance in NTS further elucidating the evolutionary mechanisms of invasive NTS phenotypes.
These results further support the use of combined genomic and phenotypic approaches to detect
and characterize atypical NTS isolates in order to advance biosurveillance efforts that inform
countermeasures aimed at controlling invasive and antimicrobial resistant NTS.