Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enteropathogenic yersiniae (Yersinia pseudotuberculosis and Yersinia enterocolitica) typically cause chronic disease as opposed to the closely related Yersinia pestis, the causative agent of bubonic plague. It is established that this difference reflects, in part, carriage by Y. pestis of a unique 9.6-kb pesticin or Pst plasmid (pPCP) encoding plasminogen activator (Pla) rather than distinctions between shared approximately 70-kb low-calcium-response, or Lcr, plasmids (pCD in Y. pestis and pYV in enteropathogenic yersiniae) encoding cytotoxic Yops and anti-inflammatory V antigen. Pla is known to exist as a combination of 32.6-kDa (alpha-Pla) and slightly smaller (beta-Pla) outer membrane proteins, of which at least one promotes bacterial dissemination in vivo and degradation of Yops in vitro. We show here that only alpha-Pla accumulates in Escherichia coli LE392/pPCP1 cultivated in enriched medium and that either autolysis or extraction of this isolate with 1.0 M NaCl results in release of soluble alpha and beta forms possessing biological activity. This process also converted cell-bound alpha-Pla to beta-Pla and smaller forms in Y. pestis KIM/pPCP1 and Y. pseudotuberculosis PB1/+/pPCP1 but did not promote solubilization. Pla-mediated posttranslational hydrolysis of pulse-labeled Yops in Y. pseudotuberculosis PB1/+/pPCP1 occurred more slowly than that in Y. pestis but was otherwise similar except for accumulation of stable degradation products of YadA, a pYV-mediated fibrillar adhesin not encoded in frame by pCD. Carriage of pPCP by Y. pseudotuberculosis did not significantly influence virulence in mice.
 ...
PMID:Expression of the plague plasminogen activator in Yersinia pseudotuberculosis and Escherichia coli. 1002 83

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.
 ...
PMID:Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. 1656 36

The YopM is an essential virulence effector produced by the bubonic plague bacterium. Yersinia pestis specific PCR gene was developed using 780 bp fragment of yopM gene. The PCR product was further cloned (in pUC57) an subcloned (pQE32 expression vector) and transformed in SG13009 E. coli host cells. The IPTG-induced recombinant protein was expressed at approximately 32 kDa region by SDS-PAGE. The recombinant protein was with 80% purity and 3mg/mL of concentration. Polyclonal and monoclonal antibodies (MAb) were generated. A total number of nine specific monoclonal antibodies obtained reacted at 43 kDa native protein of Y. pestis. Both the PCR-based assay and immunoassays were evaluated on Indian Y. pestis strains. Isolates recovered from outbreak region were positive, whereas isolates recovered from the surveillance region were negative (except one) by yopM gene PCR- and MAb-based dot-ELISA. The PCR- and ELISA-based systems developed in the present study might be utilized for detection or strain typing of Y. pestis alone or in conjunction with virulence markers such as F1 (fraction 1) and Pla (plasminogen activator).
 ...
PMID:Production and characterization of monoclonal antibodies against YopM effector protein of Yersinia pestis. 1920 12

Autotransporters, the largest family of secreted proteins in Gram-negative bacteria, perform a variety of functions, including adherence, cytotoxicity and immune evasion. In Yersinia pestis the autotransporter YapE has adhesive properties and contributes to disease in the mouse model of bubonic plague. Here, we demonstrate that omptin cleavage of Y. pestis YapE is required to mediate bacterial aggregation and adherence to eukaryotic cells. We demonstrate that omptin cleavage is specific for the Y. pestis and Y. pseudotuberculosis YapE orthologues but is not conserved in the Yersinia enterocolitica protein. We also show that cleavage of YapE occurs in Y. pestis but not in the enteric Yersinia species, and requires the omptin Pla (plasminogen activator protease), which is encoded on the Y. pestis-specific plasmid pPCP1. Together, these data show that post-translation modification of YapE appears to be specific to Y. pestis, was acquired along with the acquisition of pPCP1 during the divergence of Y. pestis from Y. pseudotuberculosis, and are the first evidence of a novel mechanism to regulate bacterial adherence.
 ...
PMID:Acquisition of omptin reveals cryptic virulence function of autotransporter YapE in Yersinia pestis. 2370 Dec 56

Various types of animal models of plague have been developed, including mice, rats, guinea pigs, and nonhuman primates. Studies have indicated that rodent and nonhuman primate models of pneumonic plague closely resemble the human disease and that the pathologic changes that occur during bubonic plague are very similar in rodents, nonhuman primates, and humans. In this section, the pathological changes caused by Y. pestis in different animal models are described. The bacterium Y. pestis causes deadly plague, whereas the other two closely related enteropathogenic Yersinia species merely cause limited gastrointestinal manifestations. Y. pestis has unique virulence mechanisms that enable it to be a successful flea-borne and highly virulent pathogen. Massive gene losses and inactivation play important roles, as well as the gene acquisitions, in the evolution process of this pathogen. Here, we summarized several newly acquired features of Y. pestis, including the unique lipid A modification, biofilm formation ability, and loss of adhesions for enteric colonization that are realized by gene inactivation and plasminogen activator and F1 capsular that are realized by gene acquisition, which contribute to the unique transmission and pathogenesis of Y. pestis.
 ...
PMID:Pathology and Pathogenesis of Yersinia pestis. 2772 64