Virulence Gene Profiling and Pathogenicity Characterization of Non-Typhoidal Salmonella Accounted for Invasive Disease in Humans

Abstract

Human infection with non-typhoidal Salmonella serovars (NTS) infrequently causes invasive systemic disease and bacteremia. To understand better the nature of invasive NTS (iNTS), we studied the gene content and the pathogenicity of bacteremic strains from twelve serovars (Typhimurium, Enteritidis, Choleraesuis, Dublin, Virchow, Newport, Bredeney, Heidelberg, Montevideo, Schwarzengrund, 9,12:l,v:- and Hadar). Comparative genomic hybridization using a Salmonella enterica microarray revealed a core of 3233 genes present in all of the iNTS strains, which include the Salmonella pathogenicity islands 1–5, 9, 13, 14; five fimbrial operons (bcf, csg, stb, sth, sti); three colonization factors (misL, bapA, sinH); and the invasion gene, pagN. In the iNTS variable genome, we identified 16 novel genomic islets; various NTS virulence factors; and six typhoid-associated virulence genes (tcfA, cdtB, hlyE, taiA, STY1413, STY1360), displaying a wider distribution among NTS than was previously known. Characterization of the bacteremic strains in C3H/HeN mice showed clear differences in disease manifestation. Previously unreported characterization of serovars Schwarzengrund, 9,12:l,v:-, Bredeney and Virchow in the mouse model showed low ability to elicit systemic disease, but a profound and elongated shedding of serovars Schwarzengrund and 9,12:l,v:- (as well as Enteritidis and Heidelberg) due to chronic infection of the mouse. Phenotypic comparison in macrophages and epithelial cell lines demonstrated a remarkable intra-serovar variation, but also showed that S. Typhimurium bacteremic strains tend to present lower intracellular growth than gastroenteritis isolates. Collectively, our data demonstrated a common core of virulence genes, which might be required for invasive salmonellosis, but also an impressive degree of genetic and phenotypic heterogeneity, highlighting that bacteremia is a complex phenotype, which cannot be attributed merely to an enhanced invasion or intracellular growth of a particular strain.

Refined Live Attenuated Salmonella enterica Serovar Typhimurium and Enteritidis Vaccines Mediate Homologous and Heterologous Serogroup Protection in Mice

“…However, only a few serovars were found to cause lethal infection in mice (see Table S1 in the supplemental material), in agreement with previous studies (37)(38)(39). It is interesting that despite the existence of scores (if not hundreds) of Salmonella serovars that have been linked to human disease, less than a handful are pathogenic in mice (40).…”

Dynamics of Salmonella Shedding and Welfare of Hens in Free-Range Egg Production Systems

“…The detection of these genes by PCR has been widely used as a predictive measure for Salmonella virulence (32,33). sptP was not amplified among S. Mbandaka and Worthington isolates.…”

Differential Single Nucleotide Polymorphism-Based Analysis of an Outbreak Caused by Salmonella enterica Serovar Manhattan Reveals Epidemiological Details Missed by Standard Pulsed-Field Gel Electrophoresis

“…A BLAST analysis of these SNPs against the Virulence Factors Database revealed three genes of particular interest: (i) fliK, coding for a flagellar hook-length control protein (41), (ii) sthD, a gene coding for a fimbrial outer membrane usher protein (42), and (iii) rfbD, coding for a UDP-galactopyranose mutase precursor involved in the synthesis of the O antigen of the lipopolysaccharide (LPS). All three proteins are virulence determinants in Salmonella (43)(44)(45)(46). WGS has already proved its usefulness for elucidating the evolutionary diversity of large populations of bacterial isolates (11,47,48).…”