title: Stazyme, a mycobacteriolytic preparation from a Staphylococcus strain, is able to break the permeability barrier in multiple drug resistant Mycobacterium avium.
abstract: As a strategy to augment the potential of existing drugs against Mycobacterium avium we investigated a mycobacteriolytic preparation (stazyme) from the Staphylococcus strain Clavelis, which results in significant mycobacterial growth inhibition. A total of 10 specific protein bands were characterized in the stazyme preparation: three bands within a major 40-60 kDa fraction, five bands within the range of 30-90 kDa, and two bands of about 12 and 14 kDa respectively. Tested at concentrations of 50 and 200 microg ml(-1) of total protein, stazyme was highly bactericidal against M. smegmatis, and bacteriostatic against M. tuberculosis and M. avium. Stazyme was able to break the permeability barrier of M. avium isolates, significantly enhancing the activity of other antituberculous drugs (ethambutol, rifampicin, and amikacin), used at sub-MIC level. Stazyme essentially possessed a lytic activity as evidenced by its ability to lyse purified M. smegmatis cell walls. This lytic activity was also confirmed on intact M. smegmatis and M. avium bacilli by transmission electron microscopy. Precise identification of this mycobacteriolytic determinant(s) in stazyme may be helpful to define novel drug targets in mycobacteria.
authors.affiliation: Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Pointe à Pitre, Guadeloupe.
authors.forename: N
authors.initials: N
authors.lastname: Rastogi
authors.forename: K S
authors.initials: KS
authors.lastname: Goh
authors.forename: S
authors.initials: S
authors.lastname: Clavel-Sérès
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001433:Bacteriolysis / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D015169:Colony Count, Microbial; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D004591:Electrophoresis, Polyacrylamide Gel; D004977:Ethambutol / Q000494:pharmacology; D007202:Indicators and Reagents; D017348:Microscopy, Electron, Scanning Transmission; D009162:Mycobacterium avium / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009170:Nontuberculous Mycobacteria / Q000187:drug effects; D012293:Rifampin / Q000494:pharmacology; D012430:Ruthenium Red; D013210:Staphylococcus / Q000201:enzymology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004338:Drug Combinations; D007202:Indicators and Reagents; D012430:Ruthenium Red; D000583:Amikacin; D004977:Ethambutol; D012293:Rifampin