Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strains of Legionella spp. produce extracellular proteases than can be detected using synthetic chromogenic peptides. Chromogenic tri- and tetrapeptides show a high degree of sensitivity, specificity and reagent stability when linked to para-nitroaniline (pNA). For example, SucOMe-Arg-Pro-Tyr.pNa (S-2586) is specifically hydrolysed by proteases of Legionella pneumophila and some other Legionella species. A paper disc method to sample protease directly from agar plates has been used to evaluate chromogenic peptides as reagents for diagnostic purposes. Strains of Legionella spp., Pseudomonas spp. and Enterobacteriaceae were examined, together with a recombinant Escherichia coli strain containing the cloned 38 kDa zinc metalloprotease from L. pneumophila, S-2586 was hydrolysed by 282 out of 283 L. pneumophila strains, and by the recombinant E. coli. Two of the six strains representing other Legionella species, and 22 of the 50 strains from the Pseudomonas group were also positive. No reaction was seen with any of the Enterobacteriaceae strains. Although there was functional homology between proteases from several bacterial groups, the high prevalence of S 2586-hydrolysing proteases within L. pneumophila indicates a potential usefulness for phenotypic identification.
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PMID:Rapid identification of Legionella pneumophila zinc metalloprotease using chromogenic detection. 203 13

The sequence of the structural gene encoding the Legionella pneumophila extracellular zinc metalloprotease has been determined and was found to possess a single large open reading frame (ORF) of 1,629 nucleotides (nt). This ORF was preceded by consensus promoter (TTAACT . . . 17 nt . . . TATAAC) and ribosome-binding (TAAGGAG) sequences. The deduced polypeptide contained a putative signal sequence and a total of 543 amino acid residues with a computed molecular size of 60,775 daltons, substantially larger than the observed 38,000 daltons of the native and recombinant proteins. A homology search revealed extensive amino acid identity with Pseudomonas aeruginosa elastase, a protein that is also encoded by an ORF substantially larger than that predicted for the mature size of the protein. The structural identity between the L. pneumophila protease and P. aeruginosa elastase was most pronounced in the regions forming the enzymatic active site of elastase. Amino acid residues constituting the active-site cleft of elastase were greater than 75% conserved. Elastase residues that interact with and mediate proteolysis of substrate peptides were 100% conserved. Competitive inhibitors of elastase and the structurally and functionally related thermolysin (phosphoramidon and a phosphoramidate analog, Z-GlyP(O)Leu-Ala), were shown to be equally potent at inhibiting the proteolytic activity of the L. pneumophila protease. These inhibitor studies along with the amino acid sequence similarities provide strong evidence that the L. pneumophila protease and P. aeruginosa elastase share a similar molecular mechanism of proteolysis.
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PMID:Legionella pneumophila zinc metalloprotease is structurally and functionally homologous to Pseudomonas aeruginosa elastase. 211 Jan 46

Approximately 4% of recipients of solid organ transplants in the United States develop bacterial pneumonia in the posttransplant period, often in the first 3 months following transplantation. The incidence of bacterial pneumonia is highest in recipients of heartlung (22%) and liver transplants (17%), intermediate in recipients of heart transplants (5%), and lowest in renal transplant patients (1 to 2%). The crude mortality of bacterial pneumonia in solid organ transplantation has exceeded 40% in most series. Beyond those risk factors identified for nosocomial pneumonia, the occurrence of primary cytomegalovirus (CMV) infection, graft rejection, maintenance antirejection therapy with prednisone, azathioprine, and antilymphocyte globulin, antirejection therapy with high-dose corticosteroids or OKT3 and splenectomy have been associated with a significantly increased risk of bacterial pneumonia in these patients. In the first 3 months posttransplant, gram-negative bacilli, Staphylococcus aureus and Legionella predominate and mortality is very high, in excess of 60%. Thereafter, bacterial pneumonias are caused primarily by Streptococcus pneumoniae and Hemophilus influenzae, with considerably lower mortality. Bacterial pneumonia must be suspected in any transplant patient presenting with fever and cough, especially associated with dyspnea or infiltrates on chest radiograph. If large numbers of bacteria and polymorphonuclear leukocytes are not visualized in respiratory secretions the work-up should proceed directly to fiberoptic bronchoscopy with bronchoalveolar lavage and/or protected brush specimen to establish the microbiologic diagnosis as accurately as possible. For presumptive gram-negative bacillary pneumonia, the initial regimen must be effective against Pseudomonas aeruginosa. Prevention of bacterial pneumonia in transplant patients must begin with immunization against S pneumoniae and Influenza A, and include precautions taken to prevent nosocomial pneumonia. It further may include measures to prevent CMV infection and the use of trimethoprim/sulfamethoxazole prophylaxis during the first year posttransplantation. Ultimately, novel technologies such as selective antimicrobial decontamination and/or protective isolation during the early postoperative period may prove effective.
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PMID:Bacterial pneumonia in solid organ transplantation. 218 17

An invasiveness-defective mutant of the fish-pathogenic bacterium Vibrio anguillarum was isolated. Compared with the wild type, this mutant had a 1,000-fold higher 50% lethal dose after immersion infection of rainbow trout, Oncorhynchus mykiss, while after intraperitoneal infection, the mutant had only a 10-fold higher 50% lethal dose. In addition, the mutant showed a lower level of protease activity. Two forms of the protease (Pa and Pb) were found after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of nonheated samples. Pa was found predominantly in protease preparations of the wild type, while Pb was the predominant form in the mutant. Conversion of Pb to Pa was observed in protease preparations after incubation at 4 degrees C. Characterization of the protease showed that it was an elastolytic enzyme which required Zn2+ for activity and Ca2+ for stability. The molecular mass of the protease was 36 kilodaltons. N-terminal amino acid sequence analysis of the protease of V. anguillarum revealed homology to the elastase of Pseudomonas aeruginosa and the protease of Legionella pneumophila.
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PMID:Identification and characterization of a zinc metalloprotease associated with invasion by the fish pathogen Vibrio anguillarum. 222 44

In a new hospital building, cold and warm water systems were examined for microbiological parameters before opening. All of the 35 sampling sites showed elevated colony counts, i.e. greater than 100 cfu/ml. 11 of these contained Legionella species at various times. While Escherichia coli, coliform bacteria and Pseudomonas aeruginosa could not be found, Legionella longbeachae serogroup 1 + 2 was identified in 13 samples. Only one sample contained Legionella pneumophila serogroup 3. Legionella species were detected using a commercial gene probe assay and culture techniques. The gene probe method proved to be superior to the culture techniques insofar as significantly positive results were obtained more frequently, and evidence for the presence of Legionella of different species and serogroups could be obtained with a single procedure. The gene probe method appears to be a suitable screening method for the detection of Legionella species.
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PMID:[The detection of legionellae in a water pipe system using gene probe technics and culture methods]. 239 93

In a previous study, all convalescent-phase sera from patients with culture-confirmed legionellosis reacted on immunoblots with a Legionella genus-wide 58-kilodalton (kDa) protein antigen (J.S. Sampson, B.B. Plikaytis, and H.W. Wilkinson, J. Clin. Microbiol. 23:92-99, 1986). The present study was done to immunologically characterize and determine the diagnostic relevance of this purified antigen. The antigen was precipitated from enriched cell extracts with ammonium sulfate and purified by high-pressure liquid chromatography. High-titered rabbit antiserum produced to the purified protein was used to show its presence on immunoblots in the 60-kDa range in 38 Legionella serogroups, representing 23 species, and in 39 non-Legionella bacteria. The antiserum was made specific for Legionella strains by sequential absorptions with Bordetella pertussis, Pseudomonas aeruginosa, and Pseudomonas fluorescens whole cells. Serum from legionellosis patients reacted with both specific and nonspecific epitopes. Results of indirect immunofluorescence experiments showed that neither specific nor nonspecific epitopes of the 60-kDa protein were surface exposed on Legionella cells and that cross-reactive epitopes were variably exposed on non-Legionella bacteria. The 60-kDa protein antigen should be useful in diagnostic tests for legionellosis if care is taken to expose cryptic epitopes and if the tests use or measure only the Legionella-specific epitopes.
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PMID:Purified 60-kilodalton Legionella protein antigen with Legionella-specific and nonspecific epitopes. 244 17

Serogroup-specificity of Legionella pneumophila is related to lipopolysaccharide (LPS), and few cross-reactions between serogroups have been observed with rabbit or monkey antisera. C57BL/6 mice were sequentially immunized with crude outer membrane fractions of L. pneumophila serogroups 1, 5, and 7, Legionella bozemanii, and Legionella micdadei. Spleen cells from these mice were then fused with the Sp2-0/Ag14 mouse myeloma cell line. Outer membrane-rich fractions and LPS were prepared from L. pneumophila serogroups 1 to 8 and other Legionella and non-Legionella species. Immunoblots of these extracts were performed with monoclonal antibody obtained from these fusions. One of these monoclonal antibodies recognized an epitope common to all tested serogroups of L. pneumophila and attached to the major constituent of the outer membrane, LPS. This antibody did not react with other Legionella species and numerous gram-negative rods other than Pseudomonas fluorescens CDC93. This monoclonal antibody may be useful in preliminary identification of L. pneumophila as an alternative to direct fluorescent-antibody testing.
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PMID:Common epitope on the lipopolysaccharide of Legionella pneumophila recognized by a monoclonal antibody. 245 35

The coumamidines are novel antibiotics with activity against a wide spectrum of aerobic Gram-positive and Gram-negative bacteria. All microbiological studies were performed on coumamidine gamma 1. The MIC90s (micrograms/ml) of coumamidine are as follows: Staphylococcus aureus 1.0, Streptococcus pyogenes 8, Enterobacteriaceae 2.0, Pseudomonas aeruginosa 8, Campylobacter jejuni and Campylobacter coli 1, Legionella pneumophila 8, Haemophilus influenzae 0.5, Neisseria gonorrhoeae 0.5. Coumamidine had MICs ranging from 8 to greater 0.5, Neisseria gonorrhoeae 0.5. Coumamidine had MICs ranging from 8 to greater than 64 for most anaerobes, except some Peptostreptococcus strains. The aminoglycoside super-sensitive strain, P. aeruginosa BMH 10, was also super-sensitive to coumamidine (MIC 0.2 micrograms/ml). Coumamidine was rapidly bactericidal for S. aureus. The viable bacterial count in logarithmic phase cultures was reduced to less than 10 cfu within 2 hours after exposure to 4 times the MIC (3.12 micrograms/ml) of coumamidine. The frequency of resistance development was less than 1 X 10(-9) for Escherichia coli and S. aureus when selected at 4 and 8 times the MIC. The Cmax in mouse serum after a single subcutaneous dose of 25 mg/kg of coumamidine was 4.5 micrograms/ml and t1/2 was 1 hour. Coumamidine is stable in serum. In mouse protection tests against S. aureus NCTC 10649 the ED50 was less than 0.6 mg/kg/day when it was administered subcutaneously at 1 and 5 hours after infection. Coumamidine was not absorbed after oral administration. The antibacterial spectrum, bactericidal activity, stability in serum and low frequency of resistance make this an interesting new class of antibiotics.
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PMID:Coumamidines, new broad spectrum antibiotics of the cinodine type. III. Microbiologic activity of coumamidine gamma 1. 249 68

Permissible conclusions both from recent available literature and our own field-study results concerning the problematic nature of microbial contamination of dental hygiene articles and the resulting possible health hazard for the consumer can be summarized as follows: Manufacturing practices as are given in the basic instructions for production sites of the cosmetic industry, render a possible degree of microbial contamination. This largely rules out the danger of infection of the consumer upon acquisition of the dental hygiene product. Secondary contamination of these products, as inevitably is the case during use of dental hygiene articles, leads to microbial colonization especially of toothbrush bristles. The extent of this colonization depends at least partially upon the utilization age of the toothbrush. Also for this reason a toothbrush should be replaced by a new one after period of three months, six months at the latest and in all cases of inflammatory changes of the mouth and throat region. The contamination of both the glass or plastic container used for rinsing the teeth after brushing or for gargling can be held within certain limits by dry storage. Only in exceptional cases do mouthwashes show a small degree of contamination. Provided they contain antimicrobial substances, no therapeutically serviceable possibilities worth mentioning follow for the reduction of oropharyngeal flora. Microbial colonization of toothpastes as a result of secondary contamination following use is observed only in exceptional cases due to their preservative content. Significant germination of stagnated residual water in waterpicks often occurs, achieving germ counts up to more than 10(7) cfu per ml. Moreover, waterpicks can represent a biotope for Pseudomonas aeruginosa, and should be used neither by patients with open wounds or mucous membrane lesions in the oropharyngeal area, nor by patients with reduced immune resistance. Manufacturers of waterpicks are urged to impede or prevent the stagnation of residual water more effectively by introducing constructive improvements. Denture and retainer cleansing agents presently on the market display a sufficient antimicrobial effect within the frame of their application, however do not meet the standards set for disinfectants. Dental hygiene products are without relevance for the epidemiology of Legionnaires' disease.
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PMID:[The significance of the contamination of dental care articles. The results of a field study]. 250 Aug 2

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.
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PMID:In vitro activity of AT-4140 against clinical bacterial isolates. 255 17


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