Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type III secretion systems enable plant and animal bacterial pathogens to deliver virulence proteins into the cytosol of eukaryotic host cells, causing a broad spectrum of diseases including bacteremia, septicemia, typhoid fever, and bubonic plague in mammals, and localized lesions, systemic wilting, and blights in plants. In addition, type III secretion systems are also required for biogenesis of the bacterial flagellum. The HrcQ(B) protein, a component of the secretion apparatus of Pseudomonas syringae with homologues in all type III systems, has a variable N-terminal and a conserved C-terminal domain (HrcQ(B)-C). Here, we report the crystal structure of HrcQ(B)-C and show that this domain retains the ability of the full-length protein to interact with other type III components. A 3D analysis of sequence conservation patterns reveals two clusters of residues potentially involved in protein-protein interactions. Based on the analogies between HrcQ(B) and its flagellum homologues, we propose that HrcQ(B)-C participates in the formation of a C-ring-like assembly.
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PMID:Structure of HrcQB-C, a conserved component of the bacterial type III secretion systems. 1469 3

Given the importance of tyrosine phosphorylation of proteins in signalling pathways, it is perhaps not surprising that protein tyrosine phosphatases (PTPs) are involved in the pathogenesis of certain human diseases. A PTP produced by the Yersinia bacteria (which can cause bubonic plague, septicemia and enteric diseases) is thought to be used as a 'weapon' against host cell functions. In addition, dysfunction of cells' endogenous PTPs may contribute to defective immune function, to cancer and to diabetes.
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PMID:Protein tyrosine phosphatases in disease processes. 1473 91

A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 x 10(8) Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.
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PMID:Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague. 1503 26

Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects rodents but is also an important zoonotic disease of humans. Bubonic plague in humans follows transmission by infected fleas and is characterized by an acute, necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal flea bite site. Septicemia rapidly follows with spread to spleen, liver, and other organs. We developed a model of bubonic plague using the inbred Brown Norway strain of Rattus norvegicus to characterize the progression and kinetics of infection and the host immune response after intradermal inoculation of Y. pestis. The clinical signs and pathology in the rat closely resembled descriptions of human bubonic plague. The bacteriology; histopathology; host cellular response in infected lymph nodes, blood, and spleen; and serum cytokine levels were analyzed at various times after infection to determine the kinetics and route of disease progression and to evaluate hypothesized Y. pestis pathogenic mechanisms. Understanding disease progression in this rat infection model should facilitate further investigations into the molecular pathogenesis of bubonic plague and the immune response to Y. pestis at different stages of the disease.
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PMID:Kinetics of disease progression and host response in a rat model of bubonic plague. 1585 43

Yersinia pestis is transmitted by fleas and causes bubonic plague, characterized by severe local lymphadenitis that progresses rapidly to systemic infection and life-threatening septicemia. Here, we show that although flea-borne transmission usually leads to bubonic plague in mice, it can also lead to primary septicemic plague. However, intradermal injection of Y. pestis, commonly used to mimic transmission by fleabite, leads only to bubonic plague. A Y. pestis strain lacking the plasmid-encoded cell-surface plasminogen activator, which is avirulent by intradermal or s.c. injection, was able to cause fatal primary septicemic plague at low incidence, but not bubonic plague, when transmitted by fleas. The results clarify a long-standing uncertainty about the etiology of primary septicemic plague and support an evolutionary scenario in which plague first emerged as a flea-borne septicemic disease of limited transmissibility. Subsequent acquisition of the plasminogen activator gene by horizontal transfer enabled the bubonic form of disease and increased the potential for epidemic spread.
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PMID:Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. 1656 36

Yersinia pestis causes bubonic plague, characterized by an enlarged, painful lymph node, termed a bubo, that develops after bacterial dissemination from a fleabite site. In susceptible animals, the bacteria rapidly escape containment in the lymph node, spread systemically through the blood, and produce fatal sepsis. The fulminant progression of disease has been largely ascribed to the ability of Y. pestis to avoid phagocytosis and exposure to antimicrobial effectors of innate immunity. In vivo microarray analysis of Y. pestis gene expression, however, revealed an adaptive response to nitric oxide (NO)-derived reactive nitrogen species and to iron limitation in the extracellular environment of the bubo. Polymorphonuclear neutrophils recruited to the infected lymph node expressed abundant inducible NO synthase, and several Y. pestis homologs of genes involved in the protective response to reactive nitrogen species were up-regulated in the bubo. Mutation of one of these genes, which encodes the Hmp flavohemoglobin that detoxifies NO, attenuated virulence. Thus, the ability of Y. pestis to destroy immune cells and remain extracellular in the bubo appears to limit exposure to some but not all innate immune effectors. High NO levels induced during plague may also influence the developing adaptive immune response and contribute to septic shock.
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PMID:Adaptive response of Yersinia pestis to extracellular effectors of innate immunity during bubonic plague. 1686 91

Bubonic plague is the most devastating acute infectious disease known to man. The causative agent, Yersinia pestis, is now more firmly entrenched in sylvatic reservoirs throughout the world than at any time in the past. Consequently, the organism increasingly causes casual human disease and is readily available for use as a bioweapon. Recent attempts to understand the severe nature of plague have focused upon its very recent divergence from Yersinia pseudotuberculosis, an etiological instrument of chronic enteropathogenic infection. This review emphasizes that the invasive nature of plague and its dissemination by fleabite is mediated by plasmids not shared by enteropathogenic yersiniae. The basis for high lethality is considered within the context of chromosomal degeneration causing loss of normal metabolic functions and modification of virulence factors, permitting a terminal anti-inflammatory phase associated with pronounced septicemia.
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PMID:How the structural gene products of Yersinia pestis relate to virulence. 1768 74

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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PMID:Imaging of bubonic plague dynamics by in vivo tracking of bioluminescent Yersinia pestis. 2249 46

Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.
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PMID:Plague: Clinics, Diagnosis and Treatment. 2772 68

Recent surveillance from the Centers for Disease Control and Prevention indicates rising annual incidence rates of Vibrio vulnificus infection. Unfortunately, this infection is often excluded from the differential diagnosis in lesser known at-risk populations. Transmission occurs via wound exposure or ingestion, with V. vulnificus foodborne illness having the highest mortality rate of all Vibrio species. Fatality rates of V. vulnificus rival those of Ebola and bubonic plague, so timely treatment is imperative. Current literature favors surgical debridement with a third-generation cephalosporin plus intravenous doxycycline or fluoroquinolone. Cephalosporin monotherapy is discouraged due to rising resistance. This case features V. vulnificus septicemia with prolonged incubation time in a noncirrhotic patient.
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PMID:Late-onset Vibrio vulnificus septicemia without cirrhosis. 3119 Nov 57


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