The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

Abstract

The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, ironlimiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ϳ90-fold increase in the 50% lethal dose (LD 50 ) relative to the Yfe ؉ Feo ؉ parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.

FeoC from Klebsiella pneumoniae Contains a [4Fe-4S] Cluster

“…Available data does not currently support the transcriptional regulator model, and we could not detect KpFeoC binding to DNA using the gel-shift or SELEX experiments (20,22); evidence supporting the G-protein modulator model is lacking. The protease inhibitor model appeared to be the only model supported by in vivo data.…”

“…Thus, FeoC was proposed to be an ironsulfur cluster-dependent transcriptional regulator directly controlling the expression of the feo operon (transcriptional regulator model) (6). However, a recent study suggested that FeoC did not regulate the feo promoter in Yersinia pestis (20), and no report has confirmed the DNA binding activity of FeoC.…”

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae

“…Y. pestis has multiple ferrous iron transporters, including Feo, Yfe, and Fet. These do not appear to be redundant, as mutations in either feo or yfe resulted in a significant growth defect (45). Similarly, Bordetella pertussis uses different systems at different times during infection (46).…”

The FeoC Protein Leads to High Cellular Levels of the Fe(II) Transporter FeoB by Preventing FtsH Protease Regulation of FeoB in Salmonella enterica

“…On the basis of these features, the FeoC protein was initially proposed as a Fe-S cluster-dependent transcription factor controlling the feo operon (2); however, a feoC mutation was shown to have no effect on transcription of the feo promoter in Yersinia pestis (7). Nonetheless, evidence suggests that the FeoC protein plays a role as the FeoB transporter, because the FeoC protein and the N-terminal domain of FeoB from Klebsiella pneumoniae were shown to interact with each other (8).…”