Role of the Yersinia pestis yersiniabactin iron acquisition system in the incidence of flea-borne plague

Abstract

Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.

Figure 1. Effect of the Y. pestis Ybt on transmission by fleas.

Incidence and time to terminal disease in mice bitten by fleas infected with Y. pestis wild type (open squares) or the Δirp2 mutant (open circles).

Figure 2. Lymph node histology of mice with terminal plague following flea-borne transmission of wild-type and Δirp2 Y. pestis.

Lymph node sections from mice infected with the wild-type strain (A to C) or with the Δirp2 strain (D to I) were strained by H&E (A, B, D, E, G and H) or by IHC using Y. pestis-specific antibody (C, F and I). Panels D, E and F and the panels G, H and I are photos of the lymph node from mouse with and without lymphadenitis respectively. Masses of bacteria, indicated by green arrowheads, stained dark brown by IHC and blue by H&E. Red arrowheads show tissue destruction in the sick mouse infected with the Δirp2 mutant. The lymph nodes (G, H and I) have an identical normal histology to uninfected lymph node . Magnification, 40x (A, D, G, C, F and I) and 400x (B, E and H).