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Antimicrobial Agents and Chemotherapy, February 2003, p. 480-488, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.480-488.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

MC21-A, a Bactericidal Antibiotic Produced by a New Marine Bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30^T, against Methicillin-Resistant Staphylococcus aureus

Alim Isnansetyo and Yuto Kamei^*

Marine and Highland Bioscience Center, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan

Received 25 June 2002/ Returned for modification 21 August 2002/ Accepted 5 November 2002

We previously reported a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30^T, which produced a bactericidal antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we purified an anti-MRSA substance (MC21-A) from the methanol extract of the cells of P. phenolica O-BC30^T and analyzed its chemical structure. MC21-A was determined to be 3,3',5,5'-tetrabromo-2,2'-biphenyldiol by spectrometric analyses. Its anti-MRSA activity against 10 clinical isolates of MRSA was comparable to that of vancomycin (MC21-A MICs, 1 to 2 µg/ml; vancomycin MICs, <0.25 to 2 µg/ml). This substance was also high active against Enterococcus serolicida, Enterococcus faecium, and Enterococcus faecalis but was less active against Streptococcus spp. A time-kill study also demonstrated that MC21-A was bactericidal and that its killing rate was much higher than that of vancomycin. The postantibiotic effect (PAE) of MC21-A against a clinical MRSA isolate, strain E 31243, was also comparable to that of vancomycin (MC21-A PAEs, 1.46 to 1.65 h; vancomycin PAEs, 0.84 to 1.43 h). However, a lysis experiment demonstrated that this substance failed to lyse MRSA cells. This substance also did not lyse human erythrocytes. A SYTOX Green staining experiment implied that this substance permeabilized the cell membrane of MRSA as its mode of action. When its activities against a hypersensitive Escherichia coli mutant (KO 1489) and wild-type strains were tested, MC21-A exhibited higher levels of activity against the former. Furthermore, MC21-A was not cytotoxic to human normal fibroblast, rat pheochromocytoma, and Vero cells at concentrations up to 50 µg/ml. These results suggest that MC21-A might be useful as a lead compound in the development of new types of anti-MRSA substances with modes of action different from those of vancomycin and teicoplanin.

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* Corresponding author. Mailing address: Marine and Highland Bioscience Center, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan. Phone: 81-955-77-4484. Fax: 81-955-77-4486. E-mail: kameiy{at}cc.saga-u.ac.jp.

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Antimicrobial Agents and Chemotherapy, February 2003, p. 480-488, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.480-488.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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