MC21-A, a bactericidal antibiotic produced by a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30(T), against methicillin-resistant Staphylococcus aureus.
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 micro g/ml; vancomycin MICs, <0.25 to 2 micro g/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 micro g/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.
Isnansetyo
Alim
A
Marine and Highland Bioscience Center, Saga University, 152-1 Shonan-cho, Karatsu, Saga 847-0021, Japan.
Kamei
Yuto
Y
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D005285:Fermentation; D006461:Hemolysis / Q000187:drug effects; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D011075:Polybrominated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D031161:Pseudoalteromonas / Q000502:physiology*; D013211:Staphylococcus aureus / Q000187:drug effects*
C476154:3,3',5,5'-tetrabromo-2,2'-biphenyldiol; D000900:Anti-Bacterial Agents; D011075:Polybrominated Biphenyls