Persistent Yersinia pestis antigens in ischemic tissues of a patient with septicemic plague

Guarner, Jeannette; Shieh, Wun‐Ju; Chu, May C.; Perlman, David C.; Kool, Jolanda; Gage, Kenneth L.; Ettestad, Paul; Zaki, Sherif R.

doi:10.1016/j.humpath.2005.05.016

Cited by 8 publications

(5 citation statements)

References 14 publications

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“…The saturation of the filtering capacity of the spleen and liver coupled with massive in situ bacterial multiplication subsequently leads to a terminal septicemia with an invasion of the entire body, as attested by a luminescent signal emitted from the whole animal. This terminal septicemic stage of bubonic plague has been largely documented, both in human victims [4], [27], [30], [31] and in non-human hosts [5], [8], [9], [29], [32], [33].…”

Section: Discussionmentioning

confidence: 99%

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

Nham¹,

Filali²,

Danne³

et al. 2012

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 99%

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

Nham¹,

Filali²,

Danne³

et al. 2012

PLoS ONE

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“…During the course of an infection with Y. pestis, cells proliferate to bacteremic levels throughout the body. Lysis of Y. pestis bacterial cells during infection contributes to septic shock and subsequent death of the host (Guarner et al, 2005). Pla, pesticin (pst) and pesticin immunity protein (pim) located on the pPCP1 plasmid are all transcribed at the host core body temperature of 37 1C (Straley and Perry, 1995;Motin et al, 2004), but only Pla has been shown to have a key role in pathogenesis (Sebbane et al, 2006;Haiko et al, 2009).…”

Section: Genomic Reduction: the Race For Virulencementioning

confidence: 99%

An additional step in the transmission of Yersinia pestis?

et al. 2011

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Plague, caused by the bacterium Yersinia pestis, is a mammalian vector-borne disease, transmitted by fleas that serve as the vector between rodent hosts. For many pathogens, including Y. pestis, there are strong evolutionary pressures that lead to a reduction in 'useless genes', with only those retained that reflect function in the specific environment inhabited by the pathogen. Genetic traits critical for survival and transmission between two environments, the rodent and the flea, are conserved in epizootic/epidemic plague strains. However, there are genes that remain conserved for which no function in the flea-rodent cycle has yet been observed, indicating an additional environment may exist in the transmission cycle of plague. Here, we present evidence for highly conserved genes that suggests a role in the persistence of Y. pestis after death of its host. Furthermore, maintenance of these genes points to Y. pestis traversing a post-mortem path between, and possibly within, epizootic periods and offering insight into mechanisms that may allow Y. pestis an alternative route of transmission in the natural environment.

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“…In the later stages of severe disease, some patients develop petechiae and purpura caused by vasculitis and disseminated intravascular coagulation, leading rarely to gangrene and a need to amputate fingers and toes. 25 A rare clinical form reported during the decade is pharyngeal plague, which presents as a sore throat with cervical lymphadenopathy after ingesting or inhaling bacteria. An outbreak in Jordan in 1997 affected 12 persons who had eaten raw or cooked camel meat from the same camel 2-4 days before the onset of symptoms 9 ; although one developed pneumonia and two underwent appendectomies, all survived after gentamicin treatment.…”

Section: Clinical Featuresmentioning

confidence: 99%

Plague Gives Surprises in the First Decade of the 21st Century in the United States and Worldwide

Butler¹

2013

The American Society of Tropical Medicine and Hygiene

111

105

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Abstract. Plague is an ancient disease caused by the bacterium Yersinia pestis and transmitted by rodent flea bites that continues to surprise us with first-ever events. This review documents plague in human cases in the 1st decade of the 21st century and updates our knowledge of clinical manifestations, transmission during outbreaks, diagnostic testing, antimicrobial treatment, and vaccine development. In the United States, 57 persons were reported to have the disease, of which seven died. Worldwide, 21,725 persons were affected with 1,612 deaths, for a case-fatality rate of 7.4%. The Congo reported more cases than any other country, including two large outbreaks of pneumonic plague, surpassing Madagascar, which had the most cases in the previous decade. Two United States scientists suffered fatal accidental exposures: a wildlife biologist, who carried out an autopsy on a mountain lion in Arizona in 2007, and a geneticist with subclinical hemochromatosis in Chicago, who was handling an avirulent strain of Y. pestis in 2009. Antimicrobial drugs given early after the onset of symptoms prevented many deaths; those recommended for treatment and prophylaxis included gentamicin, doxycycline, and fluoroquinolones, although fluoroquinolones have not been adequately tested in humans. Fleas that do not have their guts blocked by clotted blood meals were shown to be better transmitters of plague than blocked fleas. Under development for protection against bioterrorist use, a subunit vaccine containing F1 and V antigens of Y. pestis was administered to human volunteers eliciting antibodies without any serious side effects. These events, although showing progress, suggest that plague will persist in rodent reservoirs mostly in African countries burdened by poverty and civil unrest, causing death when patients fail to receive prompt antimicrobial treatment.

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Persistent Yersinia pestis antigens in ischemic tissues of a patient with septicemic plague

Cited by 8 publications

References 14 publications

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

Imaging of Bubonic Plague Dynamics by In Vivo Tracking of Bioluminescent Yersinia pestis

An additional step in the transmission of Yersinia pestis?

Plague Gives Surprises in the First Decade of the 21st Century in the United States and Worldwide

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