The plasmid-encoded Ipf and Klf fimbriae display different expression and varying roles in the virulence of Salmonella enterica serovar Infantis in mouse vs. avian hosts

Abstract

Salmonella enterica serovar Infantis is one of the prevalent Salmonella serovars worldwide. Different emergent clones of S. Infantis were shown to acquire the pESI virulence-resistance megaplasmid affecting its ecology and pathogenicity. Here, we studied two previously uncharacterized pESI-encoded chaperone-usher fimbriae, named Ipf and Klf. While Ipf homologs are rare and were found only in S. enterica subspecies diarizonae and subspecies VII, Klf is related to the known K88-Fae fimbria and klf clusters were identified in seven S. enterica subspecies I serovars, harboring interchanging alleles of the fimbria major subunit, KlfG. Regulation studies showed that the klf genes expression is negatively and positively controlled by the pESI-encoded regulators KlfL and KlfB, respectively, and are activated by the ancestral leucine-responsive regulator (Lrp). ipf genes are negatively regulated by Fur and activated by OmpR. Furthermore, induced expression of both klf and ipf clusters occurs under microaerobic conditions and at 41°C compared to 37°C, in-vitro. Consistent with these results, we demonstrate higher expression of ipf and klf in chicks compared to mice, characterized by physiological temperature of 41.2°C and 37°C, respectively. Interestingly, while Klf was dispensable for S. Infantis colonization in the mouse, Ipf was required for maximal colonization in the murine ileum. In contrast to these phenotypes in mice, both Klf and Ipf contributed to a restrained infection in chicks, where the absence of these fimbriae has led to moderately higher bacterial burden in the avian host. Taken together, these data suggest that physiological differences between host species, such as the body temperature, can confer differences in fimbriome expression, affecting Salmonella colonization and other host-pathogen interplays.

Emergence of Multidrug-Resistant Salmonella enterica Subspecies enterica Serovar Infantis of Multilocus Sequence Type 2283 in German Broiler Farms

“…We detected a specific gene pattern of virulence genes among the 15 MDR strains from the 2010s ( Table 3). We named this pattern ESIv (Emergent S. Infantis virulence) which consists of genes associated with the fimbrial clusters: K88-like fimbria (Klf) and the S. Infantis plasmid-encoded fimbria (Ipf) (Aviv et al, 2017). Moreover, the pattern includes genes encoding for the virulent yersiniabactin operon (fyuA, irp1, irp2, ybtA, ybtE, ybtP, ybtQ, ybtS, ybtT, ybtU, ybtX) and the mercury (mer) operon (merR, merT, merP, merC, merA, merD, merE) conferring mercury resistance.…”

The Typhi colonization factor (Tcf) is encoded by multiple non-typhoidal Salmonella serovars but exhibits a varying expression profile and interchanging contribution to intestinal colonization

“…21 Such discrepancies may be due to differences in the strains used and methodological approach (RT-PCR compared with lacZ reporter gene fusion). Induction of fimbria expression under oxygen-limitation was previously reported for several other fimbriae including the MR/P fimbria of uropathogenic Proteus mirabilis, type 1 fimbriae of uropathogenic E. coli 45 as well as the Klf and IpF pESI encoded fimbriae, 14 suggesting that microaerobiosis is used by different pathogens to sense the environment and regulate fimbriae expression accordingly.…”

“…This regulator is known to function as a transcriptional repressor or activator, controlling the expression of numerous operons in E. coli and Salmonella. 46 In addition to operons involved in amino acid metabolism, Lrp was previously shown to regulate different fimbrial operons including pap (P pilus) and fan (K99), 32 fim, 35,47 sfa, daa, 48 klf, 14 as well as the nonfimbrial adhesin TosA in uropathogenic E. coli. 33 The presence of six putative Lrp binding sites in the tcfA promoter region strongly suggests that Lrp repression is direct.…”

“…To identify S. Infantis regulators controlling tcf expression we screened ten null mutant strains, lacking regulators that were previously reported to be involved in oxygen homeostasis (OxyR, SoxR, ArcA, ArcB and FNR) 30 ; Salmonella pathogenicity (RpoS, PhoP, OmpR and Fur) 31 ; and the leucine-responsive regulatory protein (Lrp), which was shown to regulate different types of fimbriae in E. coli 32,33 and Salmonella. 14,34,35 Using Figure 2. The N-terminal half of TcfD is highly diverse.…”

“…It has been shown that differences in the presence of fimbriae or even allelic variation within a particular fimbria may significantly affect the interaction of Salmonella with its host. 12,[14][15][16][17][18][19] The Typhi colonization factor (Tcf) belongs to the a fimbrial clade 12 of the chaperone-usher fimbriae, which was identified in strains of typhoidal serovars including Typhi, 20 Paratyphi A, and Sendai, 17 but is absent from the genome of the ubiquitous broad-hostrange serovars Typhimurium and Enteritidis. Moreover, since Tcf displays homology to the CS1 fimbria of human-specific enterotoxigenic Escherichia coli 20 and to the cable (Cbl) pili of Burkholderia cepacia, it was suggested that Tcf plays a role in host specificity of typhoidal serovars to humans.…”