Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human isolates of Streptococcus pneumoniae tested by traditional immunochemical methods produce a protease that cleaves human immunoglobulin A1 (IgA1) into Fab and Fc fragments. The protease may be an important virulence factor, but studies of its pathogenetic significance have been hampered by lack of a suitable animal model. Since S. pneumoniae is a respiratory pathogen for several species of animals, we sought to determine whether isolates of this organism from animals with pneumococcal infection, including fatal diplococcal pneumonia, produced an IgA protease. Isolates from six animal species including the mouse, rat, dog, guinea pig, rhesus monkey, and chimpanzee were tested for protease activity against IgA preparations from the mouse, rat, dog, guinea pig, rabbit, rhesus and cynomolgus monkeys, gorilla, and human. Cleavage of IgA was demonstrated by the appearance of Fc fragments in Western blots (immunoblots) treated with specific antisera. All these isolates except that from the guinea pig produced a protease that cleaved IgA of human, rhesus monkey, and gorilla origin. Cleavage was inhibited by 5 mM EDTA. IgA cleavage from the other species could not be demonstrated. Although S. pneumoniae can colonize the respiratory tracts of several animal species, it is a significant pathogen principally of humans and some other primates. Our data suggest that some species of nonhuman primates including the rhesus monkey could be suitable for experimental studies on the significance of IgA protease in the pathogenesis of pneumococcal disease.
 ...
PMID:Production of immunoglobulin A protease by Streptococcus pneumoniae from animals. 211 67

Haemophilus pleuropneumoniae, the etiological agent of porcine contagious pneumonia, was examined for the ability to produce an immunoglobulin A (IgA) protease specific for porcine IgA. No IgA protease activity against either porcine or human IgA was detected. Furthermore, no sequence homology was found between H. pleuropneumoniae chromosomal DNA and the gene which specifies IgA protease in Haemophilus influenzae.
 ...
PMID:Examination of Haemophilus pleuropneumoniae for immunoglobulin A protease activity. 632 57

The ZmpC zinc metalloproteinase of Streptococcus pneumoniae, annotated in the type 4 genome as SP0071, was found to cleave human matrix metalloproteinase 9 (MMP-9). The previously described IgA protease activity was confirmed to be specifically linked to the IgA1-protease/SP1154 zinc metalloproteinase. MMP-9 is a protease cleaving extracellular matrix gelatin and collagen and is activated by proteolytic cleavage like most proteases. MMP-9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood-brain barrier. While TIGR4 (serotype 4) and G54 (serotype 19) pneumococcal genome strains have a highly conserved copy of zmpC, the genome of R6 (a derivative of serotype 2 D39 strain) lacks zmpC. Both the analysis for zmpC presence and MMP-9 cleavage activity in various pneumococcal strains showed correlation of ZmpC with MMP-9 cleavage activity. When assaying clinical isolates of S. pneumoniae, the zmpC gene was not found in any of the nasal and conjunctival swab isolates, but it was present in 1 out of 13 meningitis isolates and in 6 out of 11 pneumonia isolates. In a murine pneumonia model, infection with a zmpC-mutant reduced mortality at 3-4 days post-infection by 75%, when compared with infection with wild-type strains. These data indicate that the ZmpC pneumococcal protease may play a role in pneumococcal virulence and pathogenicity in the lung.
 ...
PMID:Pneumococcal zinc metalloproteinase ZmpC cleaves human matrix metalloproteinase 9 and is a virulence factor in experimental pneumonia. 1286 60

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide, and the human Ureaplasma species are most frequently isolated from the amniotic fluid and placenta in these cases. Ureaplasma colonisation is associated with infertility, stillbirth, histologic chorioamnionitis, and neonatal morbidities, including congenital pneumonia, bronchopulmonary dysplasia, meningitis and perinatal death. The human Ureaplasma spp. are separated into Ureaplasma urealyticum and Ureaplasma parvum with 14 known serotypes. The small genome has several genes, which code for surface proteins; most significantly the Multiple Banded Antigen (MBA) where an antigenic C-terminal domain elicits a host antibody response. Other genes code for various virulence factors such as IgA protease and urease. Ureaplasma spp. infection is diagnosed by culture and polymerase chain reaction (PCR) and commercial assays are available to improve turnaround time. Microbroth dilution assays are routinely used to test antimicrobial susceptibility of clinical Ureaplasma spp. especially against doxycycline, azithromycin, ofloxacin and josamycin. Resistance to macrolides, fluoroquinolones and tetracyclines has been reported. A concise review of Ureaplasma spp. and their role in pregnancy outcomes, especially preterm birth, offers insight into the early diagnosis and appropriate antibiotic therapy to prevent long-term complications of Ureaplasma spp. infections.
 ...
PMID:Ureaplasma species and preterm birth: current perspectives. 3214 97