Abstract
Since its recent emergence from the enteropathogen Yersinia pseudotuberculosis, Y. pestis, the plague agent, has acquired an intradermal (id) route of entry and an extreme virulence. To identify pathophysiological events associated with the Y. pestis high degree of pathogenicity, we compared disease progression and evolution in mice after id inoculation of the two Yersinia species. Mortality studies showed that the id portal was not in itself sufficient to provide Y. pseudotuberculosis with the high virulence power of its descendant. Surprisingly, Y. pseudotuberculosis multiplied even more efficiently than Y. pestis in the dermis, and generated comparable histological lesions. Likewise, Y. pseudotuberculosis translocated to the draining lymph node (DLN) and similar numbers of the two bacterial species were found at 24 h post infection (pi) in this organ. However, on day 2 pi, bacterial loads were higher in Y. pestis-infected than in Y. pseudotuberculosis-infected DLNs. Clustering and multiple correspondence analyses showed that the DLN pathologies induced by the two species were statistically significantly different and identified the most discriminating elementary lesions. Y. pseudotuberculosis infection was accompanied by abscess-type polymorphonuclear cell infiltrates containing the infection, while Y. pestis-infected DLNs exhibited an altered tissue density and a vascular congestion, and were typified by an invasion of the tissue by free floating bacteria. Therefore, Y. pestis exceptional virulence is not due to its recently acquired portal of entry into the host, but is associated with a distinct ability to massively infiltrate the DLN, without inducing in this organ an organized polymorphonuclear cell reaction. These results shed light on pathophysiological processes that draw the line between a virulent and a hypervirulent pathogen.
Highlights
Bubonic plague is an acute bacterial disease which, if untreated, leads to death in 50–90% of the cases [1] in generally less than 5 days [2]
To test whether a similar difference would appear after id inoculation, which most closely mimics the natural transmission mode of bubonic plague, serial dilutions of Y. pestis CO92 and Y. pseudotuberculosis IP32953 were injected id into the ear of outbred mice and lethal doses 50 (LD50) were calculated from the mortality rates after a 3 week follow-up
Two major steps in the evolution from Y. pseudotuberculosis to Y. pestis have been the acquisition of an id portal of infection and a sharp increase in virulence, raising the question of a possible causal link between the two events
Summary
Bubonic plague is an acute bacterial disease which, if untreated, leads to death in 50–90% of the cases [1] in generally less than 5 days [2]. Plague is an anthropozoonosis affecting primarily rodents [2,5] and the disease has a host-vector-host transmission cycle. The vectors are fleas which transmit the disease by intradermal (id) biting. Humans are generally contaminated through the bite of an infected rodent flea. Experimental id or subcutaneous (sc) injection of the plague agent into laboratory rodents, e.g. guinea pigs, mice and rats, causes a disease similar to naturally acquired bubonic plague [6,7,8,9,10,11,12]. The infected node increases in size and, within a few days, gives rise to the so-called bubo, hallmark of the disease. The septicemiainduced shock is believed to be the proximal cause of death
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