Abstract
Yersinia pestis dissemination in a host is usually studied by enumerating bacteria in the tissues of animals sacrificed at different times. This laborious methodology gives only snapshots of the infection, as the infectious process is not synchronized. In this work we used in vivo bioluminescence imaging (BLI) to follow Y. pestis dissemination during bubonic plague. We first demonstrated that Y. pestis CO92 transformed with pGEN-luxCDABE stably emitted bioluminescence in vitro and in vivo, while retaining full virulence. The light produced from live animals allowed to delineate the infected organs and correlated with bacterial loads, thus validating the BLI tool. We then showed that the first step of the infectious process is a bacterial multiplication at the injection site (linea alba), followed by a colonization of the draining inguinal lymph node(s), and subsequently of the ipsilateral axillary lymph node through a direct connection between the two nodes. A mild bacteremia and an effective filtering of the blood stream by the liver and spleen probably accounted for the early bacterial blood clearance and the simultaneous development of bacterial foci within these organs. The saturation of the filtering capacity of the spleen and liver subsequently led to terminal septicemia. Our results also indicate that secondary lymphoid tissues are the main targets of Y. pestis multiplication and that colonization of other organs occurs essentially at the terminal phase of the disease. Finally, our analysis reveals that the high variability in the kinetics of infection is attributable to the time the bacteria remain confined at the injection site. However, once Y. pestis has reached the draining lymph nodes, the disease progresses extremely rapidly, leading to the invasion of the entire body within two days and to death of the animals. This highlights the extraordinary capacity of Y. pestis to annihilate the host innate immune response.
Highlights
Plague is an infectious disease caused by the Gram-negative bacillus Yersinia pestis [1]
They were performed after the terminal phase of the disease, when the entire body was colonized, and the mode of Y. pestis dissemination could not be clearly established
This phenomenon is exemplified by the fact that the LD50, commonly used as a means for quantifying bacterial virulence, relies on the fact that a similar bacterial inoculum will be lethal for only half of the animals, even if they have an identical genetic background and are kept under similar conditions
Summary
Plague is an infectious disease caused by the Gram-negative bacillus Yersinia pestis [1]. Rodents are the main plague reservoir and the disease is transmitted from rodent to rodent via the bite of infected fleas [3]. Humans, which are incidental hosts of Y. pestis, are most commonly infected after the inoculation of the bacillus into the dermis during a fleabite. This mode of Y. pestis penetration generally gives rise to the development of the most common form of infection, bubonic plague, which is characterized by the appearance of a painful and inflammatory lymph node, the pathognomonic bubo. The infection spreads to various organs, leading to a terminal and fatal septicemia. In the absence of treatment, bubonic plague lethality varies from 50 to 70% [4]
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