The hydrolysis of methicillin by the penicillinase produced by 108 epidemiologically distinct methicillin-resistant strains of has been investigated. In no case is there evidence for a variant enzyme with increased efficiency of hydrolysis of methicillin. Cultures of penicillinase-negative variants of methicillin-resistant strains are heterogeneous in their resistance to methicillin. In all but one case, organisms resistant to a high concentration of methicillin revert to a heterogeneous resistance pattern on subculture in the absence of methicillin. Methicillin-resistant strains do not grow slowly in the absence of methicillin, but are more resistant to methicillin when grown at low temperature or when grown in the presence of sodium chloride. The mucopeptide of methicillin-resistant cells does not differ from that of methicillin-sensitive cells either in amount or composition. Possible mechanisms of methicillin resistance are discussed.


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