Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary tract infections (UTIs) afflict over 9 million women in America every year, often necessitating long-term prophylactic antibiotics. One risk factor for UTI is frequent sexual intercourse, which dramatically increases the risk of UTI. The mechanism behind this increased risk is unknown; however, bacteriuria increases immediately after sexual intercourse episodes, suggesting that physical manipulation introduces periurethral flora into the urinary tract. In this paper, we investigated whether superinfection (repeat introduction of bacteria) resulted in increased risk of severe UTI, manifesting as persistent bacteriuria, high titer bladder bacterial burdens and chronic inflammation, an outcome referred to as chronic cystitis. Chronic cystitis represents unchecked luminal bacterial replication and is defined histologically by urothelial hyperplasia and submucosal lymphoid aggregates, a histological pattern similar to that seen in humans suffering chronic UTI. C57BL/6J mice are resistant to chronic cystitis after a single infection; however, they developed persistent bacteriuria and chronic cystitis when superinfected 24 hours apart. Elevated levels of interleukin-6 (IL-6), keratinocyte cytokine (KC/CXCL1), and granulocyte colony-stimulating factor (G-CSF) in the serum of C57BL/6J mice prior to the second infection predicted the development of chronic cystitis. These same cytokines have been found to precede chronic cystitis in singly infected C3H/HeN mice. Furthermore, inoculating C3H/HeN mice twice within a six-hour period doubled the proportion of mice that developed chronic cystitis. Intracellular bacterial replication, regulated hemolysin (HlyA) expression, and caspase 1/11 activation were essential for this increase. Microarrays conducted at four weeks post inoculation in both mouse strains revealed upregulation of IL-1 and antimicrobial peptides during chronic cystitis. These data suggest a mechanism by which caspase-1/11 activation and IL-1 secretion could predispose certain women to recurrent UTI after frequent intercourse, a predisposition predictable by several serum biomarkers in two murine models.
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PMID:Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection. 2556 99

Klebsiella pneumoniae (Kp) reference strain Kp52.145 is widely used in experimental Klebsiella pathophysiology. Since 1935, only one other strain of the same sublineage (sequence type ST66, capsular serotype K2) was isolated (AJ210, Australia). Here, we describe a community-acquired invasive infection caused by a ST66-K2 Kp strain in France. Four hypermucoviscous Kp isolates responsible for acute otitis media, meningitis, bacteraemia and bacteriuria, respectively, were obtained from a patient with a history of chronic alcoholism and diabetes mellitus, and infected with HIV. The isolates were characterized by phenotypic and genomic methods. The four genetically identical ST66-K2 isolates presented a full antimicrobial susceptibility profile, including to ampicillin, corresponding to a single strain (SB5881), which was more closely related to AJ210 (135 SNPs) than to Kp52.145 (388 SNPs). Colibactin and yersiniabactin gene clusters were present on the integrative and conjugative element ICEKp10 in the chromosome. The two plasmids from Kp52.145 were detected in SB5881. In addition to carrying genes for virulence factors RmpA, aerobactin and salmochelin, plasmid II has acquired in SB5881, the conjugation machinery gene cluster from plasmid I. We report the first case of community-acquired infection caused by a hypervirulent ST66-K2 Kp strain in Europe. This demonstrates the long-term persistence of the high-virulence and laboratory model ST66-K2 sublineage. The combination of a conjugative apparatus and major virulence genes on a single plasmid may contribute to the co-occurrence of hypervirulence and multidrug resistance in single Kp strains.
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PMID:Community-acquired infection caused by the uncommon hypervirulent Klebsiella pneumoniae ST66-K2 lineage. 3274 55