is usually transmitted by infected fleas and produces bubonic plague, characterized by a painful, swollen lymph node, the bubo 
. Bubonic plague progresses rapidly to a life-threatening septicemia, but septicemia without a prior bubonic phase (primary septicemic plague), may also result from direct injection of plague bacilli into a blood vessel during the flea bloodmeal 
. Other less common clinical presentations that can follow flea-borne transmission include pestis minor (a benign form of bubonic plague) and carbuncular plague with or without palpable buboes 
. These rare forms of plague have not been attributed to atypical strains of Y. pestis.
However, atypical strains have been isolated from around the world and it remains unclear whether these isolates produce one or another form of plague.
Typical Y. pestis
strains form red colonies (pigmented or Pgm+
) after growth at ≤34°C on media containing Congo red, but white colonies (Pgm–
) may be isolated at a frequency of 10−4 
. Most spontaneous Pgm–
mutants result from the deletion of a 102-kb chromosomal region termed the pgm
. This locus includes the haemin storage operon (hmsHFRS
) which is essential for the pigmentation phenotype and for the production of a biofilm in the flea gut that can block normal blood feeding; the blockage of the flea's digestive tract is considered to be an important process for flea-borne transmission 
. The pgm
locus also contains the Yersinia high-pathogenicity island (HPI), which carries among other genes the irp1-irp2-ybtU-ybtT-ybtE,
and the psn
loci that encode the yersiniabactin (Ybt) siderophore-based iron acquisition and transport system. The irp
genes encode the high molecular weight proteins (HMWP) 1 and 2 which act in concert with YbtU, YbtE, YbtS and probably YbtT to synthesize the Ybt siderophore 
. Ybt is secreted, acquires iron from transferrin and lactoferrin in host tissues, then is transported back into Y. pestis
by the TonB-dependent outer membrane receptor Psn and the inner membrane ABC-transporter YbtP-YbtQ. A critical role of the Ybt system in bubonic plague is indicated by the fact that Ybt– Y. pestis
strains are essentially avirulent by the subcutaneous inoculation route that mimics the flea bite, although these strains retain complete or nearly complete virulence when inoculated intravenously 
. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, in the draining lymphatic system, and/or in the lymph nodes, suggesting that Ybt would be an essential virulence factor for flea-borne bubonic plague.
Despite the importance of the Hms and Ybt system for flea-borne transmission and for disease in bubonic plague models, respectively, the pgm
locus is subject to complete or partial loss at relatively high frequency by genomic rearrangements; and Pgm–
strains from natural plague foci have been described 
. Furthermore, human cases of plague have been associated with non-pigmented strains 
. Altogether, the data prompted us to assess the role of the Ybt system in plague epidemiology and pathogenesis in the natural context of transmission by flea bite.