Molecular design of multifunctional antibacterial agents against methicillin resistant Staphylococcus aureus (MRSA).
Antibacterial activity of a series of alkyl gallates (3,4,5-trihydroxybenzoates) against Gram-positive bacteria, especially methicillin resistant Staphylococcus aureus (MRSA) strains was evaluated. Gram-positive bacteria are all susceptible to alkyl gallates. Dodecyl gallate was the most effective against MRSA ATCC 33591 strain with the minimum bactericidal concentration (MBC) of 25 microg/mL (74 microM). The time-kill curve study showed that dodecyl gallate was bactericidal against this MRSA strain at any growth stage. This activity was observed even in the chloramphenicol-treated cells, but the rate of decrease of cell number was slower than that in the exponentially growing cells. The bactericidal activity of medium-chain alkyl gallates was noted in combination with their ability to disrupt the native membrane-associated function nonspecifically as surface-active agents (surfactants) and to inhibit the respiratory electron transport. Subsequently, the same series of alkyl protocatechuates (3,4-dihydroxybenzoates) were studied and the results obtained are similar to those found for alkyl gallates. The length of the alkyl chain is not a major contributor but is related to the activity.
Kubo
Isao
I
Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3112, USA. ikubo@uclink.berkeley.edu
Fujita
Ken-ichi
K
Nihei
Ken-ichi
K
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D015195:Drug Design; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013501:Surface-Active Agents / Q000737:chemistry
D000900:Anti-Bacterial Agents; D013501:Surface-Active Agents; C008259:lauryl gallate; D005707:Gallic Acid