An evolved oxazolidinone with selective potency against Mycobacterium tuberculosis and gram positive bacteria

• Innovation of new antibacterials to treat drug resistant infections is necessary.
• Two evolved oxazolidinone were developed and their potencies were assessed.
• T145, inhibited growth of a range of bacterial pathogens with sub μg/ml potencies.
• T145 is bactericidal against M. tuberculosis but bacteriostatic against E. faecalis and S. aureus.
• T145 minimizes selection of spontaneous resistant mutants.

Innovation of new antibacterials that are effective against strains that have developed resistance to existing drugs would strengthen our ability to treat and subsequently control spread of pathogenic bacteria. Increasing incidence of infections with drug resistant bacteria has become a common occurrence in recent times. We have developed an evolved oxazolidinone, T145, which inhibits growth of Enterococcus faecalis, Staphylococcus aureus and Mycobacterium tuberculosis (Mtb) with sub μg/ml potencies that are potentially therapeutically valuable. The oxazolidinone is bactericidal against Mtb but bacteriostatic against E. faecalis and S. aureus. In addition to therapeutically valuable potency and bactericidal activity against Mtb, T145 minimizes selection of spontaneous resistant mutants, a trait that prolongs longevity of a drug in clinical use.

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