Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preterm delivery remains a preeminent problem in reproductive and pediatric care worldwide. Recent data suggest that cervicovaginal microflora and/or the inflammatory response they engender produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be "recognized pathogens" and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Quantitative, as well as qualitative aspects of cervicovaginal microflora may be important. Multiple cervicovaginal microorganisms produce IgA protease, neuraminidase, and mucinase which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can focally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, as well as platelet-activating factor (PAF) and lymphokines which can also initiate or further potentiate labor-inducing mechanisms. Recognition of microbe-induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women with preterm labor. Further microbiological and clinical studies are ongoing. "Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics."
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PMID:Prevention of preterm birth: new initiatives based on microbial-host interactions. 327 1

The literature dealing with the pathogenicity of anaerobic gram-negative rods in humans is reviewed. Knowledge concerning definite pathogenic mechanisms is, at best, cursory. There is evidence that encapsulation plays a role in the pathogenicity of Bacteroides fragilis and some of the black-pigmented Bacteroides. A range of enzymes, among them collagenase and IgA protease, are produced by several Bacteroides species. Supernatants of Fusobacterium necrophorum cultures may be leukotoxic. Synergism between anaerobic gram-negative rods and other bacterial species has been demonstrated in experimental animals.
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PMID:Pathogenicity of anaerobic gram-negative rods: possible mechanisms. 672 37

Proteus mirabilis, a motile gram-negative bacterium, is a principal cause of urinary tract infections in patients with functional or anatomical abnormalities of the urinary tract or those with urinary catheters in place. Thus far, virulence factors including urease, flagella, haemolysin, various fimbriae, IgA protease and a deaminase have been characterized based on the phenotypic traits conferred by these proteins. In this study, an attempt was made to identify new virulence genes of P. mirabilis that may not have identifiable phenotypes using the recently described technique of signature-tagged mutagenesis. A pool of chromosomal transposon mutants was made through conjugation and kanamycin/tetracycline selection; random insertion was confirmed by Southern blotting of chromosomal DNA isolated from 16 mutants using the aphA gene as a probe. From the total pool, 2.3% (9/397) auxotrophic mutants and 3.5% (14/397) swarming mutants were identified by screening on minimal salts agar and Luria agar plates, respectively. Thirty per cent of the mutants, found to have either no tag or an unamplifiable tag, were removed from the input pool. Then 10(7) c.f.u. from a 96-mutant pool (approximately 10(5) c.f.u. of each mutant) were used as an input pool to transurethrally inoculate seven CBA mice. After 2 d infection, bacteria were recovered from the bladders and kidneys and yielded about 10(5) c.f.u. as an output pool. Dot blot analysis showed that two of the 96 mutants, designated B2 and B5, could not be hybridized by signature tags amplified from the bladder output pool. Interrupted genes from these two mutants were cloned and sequenced. The interrupted gene in B2 predicts a polypeptide of 37.3 kDa that shares amino acid similarity with a putative protease or collagenase precursor. The gene in B5 predicts a polypeptide of 32.6 kDa that is very similar to that encoded by ORF284 of the rpoN operon controlling expression of nitrogen-regulated genes from several bacterial species. The virulence of the two mutants was tested further by co-challenging CBA mice with each mutant and the parental strain. After 1 week of infection, the B2 and B5 mutants were recovered in numbers 100-fold and 1000-fold less than the parental strain, respectively. Using an in vitro assay, it was shown that the B2 mutant had significantly less (P = 0.0001) extracellular protease activity than the wild-type strain. These findings demonstrate that signature-tagged mutagenesis is a viable approach to identify bacterial genes associated with the ability to infect the urinary tract.
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PMID:Identification of protease and rpoN-associated genes of uropathogenic Proteus mirabilis by negative selection in a mouse model of ascending urinary tract infection. 1020 98