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)

The omptins are a family of enterobacterial surface proteases/adhesins that share high sequence identity and a conserved beta-barrel fold in the outer membrane. The omptins are multifunctional, and the individual omptins exhibit differing virulence-associated functions. The Pla plasminogen activator of Yersinia pestis contributes by several mechanisms to bacterial invasiveness and the systemic, uncontrolled proteolysis in plague. Pla proteolytically activates the human proenzyme plasminogen and inactivates the antiprotease alpha2-antiplasmin, and its binding to laminin localizes the uncontrolled plasmin activity onto basement membranes. These properties enhance bacterial migration through tissue barriers. Pla also degrades circulating complement proteins and functions in bacterial invasion into human epithelial cells. PgtE of Salmonella enterica and OmpT of Escherichia coli have been shown to degrade cationic antimicrobial peptides from epithelial cells or macrophages. PgtE and SopA of Shigella flexneri appear important in the intracellular phases of salmonellosis and shigellosis, whereas functions of OmpT have mainly been associated with protein degradation in E. coli cells. The differing virulence roles and functions have been attributed to minor sequence variations at the surface-exposed regions important for substrate recognition, to the dependence of omptin functions on lipopolysaccharide, and to the different regulation of omptin expression.
 ...
PMID:The omptin family of enterobacterial surface proteases/adhesins: from housekeeping in Escherichia coli to systemic spread of Yersinia pestis. 1529 49

Monoclonal antibodies (MAbs) were generated against the recombinant plasminogen activator (Pla) protein of Yersinia pestis. These MAbs detected Pla in all the 18 isolates of Y. pestis obtained from the sputum of pneumonic plague patients and from the liver and spleen of rodents from plague-affected areas of India during 1994-1995 as well as in seven of the eight isolates obtained from rodents in the surveillance regions of Hosur and Palmner in India during 1998 by simple dot-ELISA. In immunoblotting, the MAbs reacted with the Pla antigen only in Y. pestis isolates at 37 and 35kDa region. These monoclonal antibodies, being strictly specific, can be used for detecting Y. pestis isolates that are Fraction 1 antigen-negative. Also, the radiolabelled pla fragment hybridized specifically to the representative DNA samples of Y. pestis isolates.
 ...
PMID:Molecular detection of Yersinia pestis isolates of Indian origin by using Pla specific monoclonal antibodies. 1558 89

To study the possible mechanism of extracellular resistance to phagocytes developed by Yersinia pestis in the early stage of plague infection, the behaviour of two Y. pestis strains, the vaccine EV-76 and fully virulent 231 (LD(50), 10 c.f.u.), was studied in-depth after cultivation in vitro at the host temperature in conditions simulating the bloodstream environment of mammals. For this, two standard basal media supplemented with calcium and glucose in appropriate concentrations were employed: Hottinger broth, routinely used for growth of Y. pestis in vitro, and RPMI 1640, simulating human extracellular fluid. Although both media permitted Y. pestis to achieve the resistant state, RPMI enabled significantly higher bacterial proliferation and increased modifications in the production of the principal surface antigens that affect the relevant phenotype characteristics. In general, our results indicate that the Y. pestis bacteria in the resistant state do not produce species-specific antigens, i.e. fraction 1 or F1, 'murine' toxin or Ymt, plasminogen activator (Pla) and any surface-specific polysaccharides, resulting in unmasking of the cross-reactive epitopes of lipid A in reduced Y. pestis lipopolysaccharide. This may produce mimicry by Y. pestis of some human tissue and blood cell components, with no immune response and inflammation at the site of infection at the early stage, which enables Y. pestis to survive, extensively multiply and spread into the circulation.
 ...
PMID:Antigenic and phenotypic modifications of Yersinia pestis under calcium and glucose concentrations simulating the mammalian bloodstream environment. 1582 19

Yersinia pestis plasminogen activator (Pla), a surface virulence factor contributes to the highly invasive nature of the pathogen by binding various tissue matrix components. In this study we characterised the laminin-binding site(s) of Pla via phage display and alanine-scanning mutagenesis. Previously we isolated 18 different heptamer peptide sequences from a phage display library with biopanning on laminin, and have shown that two of them with sequences of WSLLTPA or YPYIPTL completely inhibited laminin binding of a Pla-expressing recombinant Escherichia coli strain. These phages themselves strongly bound laminin in an ELISA assay utilising horseradish peroxidase-labelled anti-M 13 antibody. In the present study, with the application of synthetic peptides, a 55% and a 33% inhibition was demonstrated using WSLLTPA and YPYIPTL, respectively. Peptide pattern alignment showed two homologous regions for WSLLTPA and one for YPYIPTL inside the Pla sequence. Amino acids were changed for alanine in one of the WSLLTPA regions and in the YPYIPTL region in order to prove the role of the LTP/PTL motifs in laminin binding. Of the four constructed mutants, the triple mutant L65A-T66A-L67A in the WSLLTPA region and the double mutant G178A-L179A in the YPYIPTL region decreased the laminin binding capacity of the Pla-expressing recombinant E. coli by about 50%.
 ...
PMID:Identification of laminin-binding motifs of Yersinia pestis plasminogen activator by phage display. 1596 69

The Yersinia pestis proteome was studied as a function of temperature and calcium by two-dimensional differential gel electrophoresis. Over 4,100 individual protein spots were detected, of which hundreds were differentially expressed. A total of 43 differentially expressed protein spots, representing 24 unique proteins, were identified by mass spectrometry. Differences in expression were observed for several virulence-associated factors, including catalase-peroxidase (KatY), murine toxin (Ymt), plasminogen activator (Pla), and F1 capsule antigen (Caf1), as well as several putative virulence factors and membrane-bound and metabolic proteins. Differentially expressed proteins not previously reported to contribute to virulence are candidates for more detailed mechanistic studies, representing potential new virulence determinants.
 ...
PMID:Proteomic characterization of Yersinia pestis virulence. 1629 90

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

A multiplexed, 4-target real-time polymerase chain reaction (PCR) assay for the detection and characterization of Yersinia pestis was designed and optimized for respiratory and environmental samples. The target sequences include the entF3 gene of the chromosome, pla (plasminogen activator) on the pPCP1 virulence plasmid, caf1 (F1 capsule antigen) on the pMT1 virulence plasmid, and a region located on the pCD1 plasmid. The sensitivity of this assay was determined to be less than 85 CFU per reaction for each specimen type analyzed. This assay was also determined to be 100% specific with strains of Y. pestis, 9 additional Yersinia species, and related enteric and respiratory organisms. The results show that this multiplex real-time PCR assay using TaqMan(R) (Roche Molecular Systems, Inc., Alameda, CA) chemistry is sensitive and specific, requires minimal sample input, and can yield results in approximately 4 h. This assay is the first 4-target multiplex real-time PCR assay for Y. pestis in which detection and virulence assessment of Y. pestis can occur in one reaction, from clinical and environmental samples.
 ...
PMID:Development and evaluation of a 4-target multiplex real-time polymerase chain reaction assay for the detection and characterization of Yersinia pestis. 1694 84

Bacterial pathogens have frequently evolved and maintained the capacity to engage and/or activate hemostatic system components of their vertebrate hosts. Recent studies of mice with selected alterations in host plasminogen and other hemostatic factors have begun to reveal a seminal role of bacterial plasminogen activators and fibrin clearance in microbial pathogenesis. Bacterial pathogens appear to exploit host plasmin-mediated proteolysis to both support microbial dissemination and evade innate immune surveillance systems. The contribution of bacterial plasminogen activation to the evasion of the inflammatory response is particularly conspicuous with the plague agent, Yersinia pestis. Infection of control mice with wild-type Y. pestis leads to the formation of widespread foci containing massive numbers of free bacteria with little inflammatory cell infiltrate, whereas the loss of either the bacterial plasminogen activator, Pla, or the elimination of host plasminogen results in the accumulation of robust inflammatory cell infiltrates at sites of infection and greatly improved survival. Interestingly, fibrin(ogen) deficiency undermines the local inflammatory response observed with Pla-deficient Y. pestis and effectively eliminates the survival benefits posed by the elimination of either host plasminogen or bacterial Pla. These studies, and complementary studies with other human pathogens, illustrate that plasminogen and fibrinogen are extremely effective modifiers of the inflammatory response in vivo and critical determinants of bacterial virulence and host defense. Detailed studies of the inflammatory response in mice with genetically-imposed modifications in coagulation and fibrinolytic factors underscore the regulatory crosstalk between the hemostatic and immune systems.
 ...
PMID:Fibrin and fibrinolysis in infection and host defense. 1763 5

Horizontal gene transfer events followed by proper regulatory integration of a gene drive rapid evolution of bacterial pathogens. A key event in the evolution of the highly virulent plague bacterium Yersinia pestis was the acquisition of plasmid pPCP1, which carries the plasminogen activator gene, pla. This promoted the bubonic form of the disease by increasing bacterial dissemination from flea bite sites and incidentally enhanced replication in respiratory airways during pneumonic infection. We determined that expression of pla is controlled by the global regulator cyclic AMP (cAMP) receptor protein (Crp). This transcription factor is well conserved among distantly related bacteria, where it acts as a soluble receptor for the ubiquitous signaling molecule cAMP and controls a global network of metabolic and stress-protective genes. Crp has a similar physiological role in Y. pestis since loss of its function resulted in an inability to metabolize a variety of nonglucose substrates. Activation of pla expression requires a transcription activation element of the pla promoter that serves as a Crp binding site. Crp interaction with this site was demonstrated to occur only in the presence of cAMP. Alteration of the Crp binding site nucleotide sequence prevented in vitro formation of Crp-DNA complexes and inhibited in vivo expression of pla. The placement of pla under direct regulatory control of Crp highlights how highly adapted pathogens integrate laterally acquired genes to coordinate virulence factor expression with global gene networks to maintain homeostasis through the infectious life cycle.
 ...
PMID:Direct transcriptional control of the plasminogen activator gene of Yersinia pestis by the cyclic AMP receptor protein. 1793 99

Unlike the classical Yersinia pestis strains, members of an atypical group of Y. pestis from Central Asia, denominated Y. pestis subspecies caucasica (also known as one of several pestoides types), are distinguished by a number of characteristics including their ability to ferment rhamnose and melibiose, their lack of the small plasmid encoding the plasminogen activator (pla) and pesticin, and their exceptionally large variants of the virulence plasmid pMT (encoding murine toxin and capsular antigen). We have obtained the entire genome sequence of Y. pestis Pestoides F, an isolate from the former Soviet Union that has enabled us to carryout a comprehensive genome-wide comparison of this organism's genomic content against the six published sequences of Y. pestis and their Y. pseudotuberculosis ancestor. Based on classical glycerol fermentation (+ve) and nitrate reduction (+ve) Y. pestis Pestoides F is an isolate that belongs to the biovar antiqua. This strain is unusual in other characteristics such as the fact that it carries a non-consensus V antigen (lcrV) sequence, and that unlike other Pla(-) strains, Pestoides F retains virulence by the parenteral and aerosol routes. The chromosome of Pestoides F is 4,517,345 bp in size comprising some 3,936 predicted coding sequences, while its pCD and pMT plasmids are 71,507 bp and 137,010 bp in size respectively. Comparison of chromosome-associated genes in Pestoides F with those in the other sequenced Y. pestis strains reveals differences ranging from strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. There is a single approximately 7 kb unique region in the chromosome not found in any of the completed Y. pestis strains sequenced to date, but which is present in the Y. pseudotuberculosis ancestor. Taken together, these findings are consistent with Pestoides F being derived from the most ancient lineage of Y. pestis yet sequenced.
 ...
PMID:Pestoides F, an atypical Yersinia pestis strain from the former Soviet Union. 1796 1


<< Previous 1 2 3 4 5 6 7 8 Next >>