Genomic characterization of Salmonella Uzaramo for human invasive infection

Abstract

Salmonella is composed of a wide variety of serovars, causing human self-limited gastrointestinal illnesses or invasive infections. Invasive non-typhoidal Salmonella (iNTS) is well documented, with high mortality for children and immunocompromised adults in sub-Saharan Africa and has recently been reported in Southeast Asia. However, iNTS in China remains unknown. In May 2019, a case of invasive infection caused by Salmonella enterica serovar Uzaramo (S. Uzaramo) was reported for the first time in China. Phylogenomic analysis was performed by genomic sequencing the available contextualized isolates, which separated the two Chinese strains into different sublineages. Both phenotypic and genomic characterization demonstrated that the S. Uzaramo isolates showed in general low antimicrobial resistance potential, except one isolated from lake-water in China. Additional comparative genomic analysis and Caenorhabditis elegans killing assays suggested a unique combination of virulence factors, including typhoid toxin and tcf fimbrial adhesin, which might play a role in the invasive infection. This study highlights that the transparency of global surveillance genomic data could accelerate understanding of virulence and antimicrobial resistance makeup of a previously unknown threat.

Keywords: Salmonella Uzaramo; bloodstream infection; foodborne transmission; sublineage; whole genome sequencing.

Fig. 1.

The genomic and genetic diversity of Salmonella Uzaramo isolates. (a) PFGE (with XbaI) and antimicrobial resistance profile of the two Chinese isolates. The antimicrobial resistance test was conducted by a broth MIC assay and interpreted according to EUCAST. The detected antimicrobials with resistance were as follows: streptomycin (STR), chloramphenicol (CHL), ciprofloxacin (CIP), nalidixic acid (NAL), ceftiofur (CF), ceftaroline (CPT), tetracycline (TET), sulfisoxazole (SFX) and trimethoprim/sulfamethoxazole (SXT). (b) The phylogenomic relationship among the S. Uzaramo isolates. The 14 S. Uzaramo isolates were grouped into two sublineages, with ST4543 and ST3269 belonging to Ⅰ, and ST1305 and the novel sequence type (ST) belonging to Ⅱ. The ecological traits for STs or sublineages are labelled with the corresponding symbols. Strains AUG147 and S0749 were used as the reference and outgroup control, respectively. Bar, number of substitutions per nucleotide, corresponding to the evolutionary distance. Asterisks indicate the two Chinese isolates in this study.

Fig. 2.

Comparison of three Salmonella isolates between two serovars in the C. elegans killing assay. C. elegans (n=30 for each group) was fed with two Salmonella Typhimurium strains (14 028, SL1344) and two Salmonella Uzaramo strains (U301 from sublineage II, U302 from sublineage I) to evaluate the survival percentage across ten continuous days. Both U301 and U302 had higher killing rates, with statistically significant difference compared with Typhimurium strains 14 028 and SL1344. Escherichia coli OP50 was used as the internal control.