Dynamics Of Resistance Plasmids Of Salmonella Enterica Serovar Typhi In Kibera, An Urban Slum Where High Burden Of Typhoid Fever Has Been Described

Abstract

Background Multidrug resistance (MDR) in Salmonella enterica serovar Typhi is mainly plasmid-mediated, yet, little is known of the plasmid dynamics in typhoid endemic settings. Methods We used whole genome sequence data from 304 (81.9%, n=371) bacteremic S. Typhi, isolated during an 11-year period (2007-2017) in Kibera, an urban informal settlement in Nairobi, Kenya. Sequences were analyzed for plasmid replicon families, transposons, integrons, insertion sequences (IS) and resistance genes. Temporal changes in identified plasmid replicons were compared with typhoid incidence trends. Results A previously described IncHI1-PST 6 plasmid carrying an IS1 composite transposon with a partial IncQ1 replicon, streptomycin (aph(3'')-Ib), kanamycin (aph(6)-Id), ampicillin (blaTEM-1b), chloramphenicol (catA1), trimethoprim (dfrA7), and sulfonamide (sul1 and sul2) resistance genes, dominated until 2013. Chromosomal integrations of the transposon were observed at cyaA and uxuA intergenic regions, and often coincided with loss of the IncHI1 plasmid. Plasmid-free strains were commonly identified during periods of decreased typhoid fever incidence. Conclusion We show expansion of plasmid-free strains with a chromosomally integrated MDR composite transposon. The strains coincided with periods of decreased typhoid incidence. Absence of the IncHI1 plasmid could potentially allow the strains to acquire additional plasmid-mediated resistance. Surveillance for resistance plasmids in areas with a high burden of typhoid fever can help inform efforts to control multidrug resistance.