Identification and characterization of Epp, the secreted processing protease for the Vibrio anguillarum EmpA metalloprotease.

The zinc metalloprotease EmpA is a virulence factor for the fish pathogen Vibrio anguillarum. Previous studies demonstrated that EmpA is secreted as a 46-kDa proenzyme that is activated extracellularly by the removal of an approximately 10-kDa propeptide. We hypothesized that a specific protease is responsible for processing secreted pro-EmpA into mature EmpA.

Pyrrolidine dithiocarbamate and diethyldithiocarbamate are active against growing and nongrowing persister Mycobacterium tuberculosis.

Diethyldithiocarbamate (DETC) and pyrrolidine dithiocarbamate (PDTC) were highly active against tubercle bacilli, with MICs of 8 microg/ml and 0.13 microg/ml, respectively. DETC and PDTC were active against old cultures, enhanced pyrazinamide or pyrazinamide/rifampin activity, and had serum inhibitory titers of 1:2 and 1:4, respectively, in mice given 100 mg/kg orally.

Activity of ketoconazole against Mycobacterium tuberculosis in vitro and in the mouse model.

There is an urgent need for the development of new drugs that are active against drug-resistant Mycobacterium tuberculosis strains and can shorten tuberculosis (TB) therapy. It has previously been reported that the azole class of antifungals has anti-TB activity in vitro. This study evaluated ketoconazole (KTC) for activity against M.

Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis.

Objectives: Aspirin (acetylsalicylic acid) or ibuprofen [2-(4-isobutyl-phenyl)-propionic acid] was administered to mice undergoing treatment of tuberculosis infection with pyrazinamide to determine if these non-steroidal anti-inflammatory drugs (NSAIDs) enhance pyrazinamide activity in vivo.

Methods: BALB/c mice were infected with Mycobacterium tuberculosis H37Rv through aerosol exposure. Mice were treated orally with aspirin, ibuprofen or pyrazinamide, alone and in combination.

Aspirin antagonism in isoniazid treatment of tuberculosis in mice.

Salicylate has previously been shown to reduce the susceptibility of Mycobacterium tuberculosis to several drugs in vitro. In this study, aspirin, a salicylate anti-inflammatory, antagonized isoniazid treatment of murine pulmonary tuberculosis, whereas the nonsalicylate ibuprofen did not. These results may have implications on concurrent administration of anti-inflammatory and antituberculosis drugs.

Regulation of the Vibrio anguillarum metalloprotease EmpA by posttranslational modification.

The zinc metalloprotease EmpA is a virulence factor in the fish pathogen Vibrio anguillarum. Previous studies have shown that two strains of V. anguillarum regulate empA differently.

Gel shift analysis of the empA promoter region in Vibrio anguillarum.

Background: The induction of metalloprotease encoded by empA in Vibrio anguillarum occurs at high cell density in salmon intestinal mucus. Previously we have shown that there are significant differences in empA expression in two strains of V. anguillarum, M93Sm and NB10.

Regulation of Vibrio anguillarum empA metalloprotease expression and its role in virulence.

Atlantic salmon (Salmo salar) were challenged with Vibrio anguillarum strains M93Sm and NB10 and empA null mutants M99 and NB12. Both wild types were virulent when administered by intraperitoneal (i.p.