Functional protective role for mucin glycosylated repetitive domains

Mucins carry out a number of protective roles, some of which are more easily studied than others. One mucin function is believed to be the protection of the mucosal epithelium against acidic and proteolytic damage in the stomach and intestines. In the present work, a portion of stomach mucin tandem repeat sequence (Muc6) was joined to the catalytic domain of a reporter enzyme [human milk cholesterol esterase (CE)] to determine whether the former can protect the latter protein from damage. This Muc6 domain replaced a unique series of glycosylated C-terminal repeats normally present in CE. The chimeric protein (CE/Muc6) was expressed in two different cell lines and its properties compared to recombinant full-length CE and a truncated version of CE which contained only the catalytic domain (CE/trunc). Results showed that both CE and CE/Muc6 were resistant to denaturation by acid and to proteolysis by pepsin at low pH values or by pancreatic proteases compared to CE/trunc. Thus, a stomach Muc6 domain is sufficient to confer stability on the CE catalytic domain, demonstrating a protective effect by a glycosylated mucin sequence

Twelve Years Of Fluconazole In Clinical Practice: Global-Trends In Species Distribution And Fluconazole Susceptibility Of Bloodstream Isolates Of Candida

We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI)isolates ofCandidaspp. collected from 250 medical centres in 32 nations over a 10-year period from 1992through 2001. The species included 3401C. albicans, 984C. glabrata, 796C. parapsilosis, 585C. tropicalis,153C. krusei,67C. lusitaniae,48C. guilliermondii,10C. famata,10C. kefyr, sixC. pelliculosa, fiveC. rugosa,fourC. lipolytica, threeC.dubliniensis, threeC. inconspicua, twoC. sakeand one isolate each ofC. lambica,C. norvegensisandC. zeylanoides. Minimum inhibitory concentration determinations were made usingthe National Committee for Clinical Laboratory Standards reference broth microdilution method.Variation in the rank order and frequency of the different species ofCandidawas observed over time andby geographic area. The proportion of BSI due toC. albicansandC. glabrataincreased andC. parapsilosisdecreased over time in Canada, the USA and Europe.C. glabratawas an infrequent cause of BSI in LatinAmerica and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observedamong isolates ofC. albicans,C. tropicalisandC. parapsilosis. These species accounted for 78%of all BSIand remained highly susceptible (91–100%susceptible) to fluconazole from 1992 to 2001 irrespective ofgeographic origin. The prevalence of fluconazole resistance amongC. glabrataisolates was variable bothover time and among the various countries and regions. Resistance to fluconazole amongC. glabrataisolates was greatest in the USA and varied by US census region (range 0–23%). These observations aregenerally encouraging relative to the sustained usefulness of fluconazole as a systemically activeantifungal agent for the treatment of candida BSI.Scopu