Stazyme, a mycobacteriolytic preparation from aStaphylococcusstrain, is able to break the permeability barrier in multiple drug resistantMycobacterium 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.

Mannich Ketones as Possible Antimycobacterial Agents

“…The ruthenium red (RR) cytochemical staining under a transmission electron microscope permits the visualisation of both the mycobacterial cell envelope and the general bacterial morphology. The bacteria had a characteristic trilaminar cell wall made up of a basal peptidoglycan (PG) layer, intermediate electron‐transparent layer (ETL) and an outer layer (OL) which specifically reacted with the RR cytochemical staining (Fig. ).…”