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    In vitro and in vivo activities of antibiotic PM181104

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    Antimicrob_Agents_Chemotherapy_57_5315a.pdf (500.6Kb)
    Date
    2013
    Author
    Mahajan, G.B.
    Thomas, B.
    Parab, R.
    Patel, Z.E.
    Kuldharan, S.
    Yemparala, V.
    Mishra, P.D.
    Ranadive, P.
    DeSouza, L.
    Pari, K.
    Sivaramkrishnan, H.
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    Abstract
    Drug resistance has become a global threat that, if not addressed, may return us to the preantibiotic era. A way to overcome the problem of growing incidence of global antibiotic resistance is to introduce compounds belonging to classes that are new to the clinic. During a screening of the marine microbial extract library for new antibiotics, one of the extracts showed promising antibacterial activity against Gram-positive organisms. Bioactivity-guided isolation and characterization of active metabolites led to the discovery of a novel thiazolyl cyclic-peptide antibiotic, PM181104. It was isolated and characterized from a marine sponge-associated actinobacterium strain of the genus Kocuria (MTCC 5269). The compound exhibited a potent in vitro antibacterial activity against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The MIC values evaluated for the compound were found to be in the single-digit nanomolar range. In in vivo studies of PM181104 in a BALB/c murine septicemia model, the compound displayed 100% effective dose (ED100) values of 2.5 and 5.0 mg/kg of body weight against MRSA and 10.0 mg/kg against VRE. In this report, in vitro and in vivo studies of PM181104 are described
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    http://drs.nio.org/drs/handle/2264/4401
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