Suppression of intrinsic resistance to penicillins in Staphylococcus aureus by polidocanol, a dodecyl polyethyleneoxid ether.
With polidocanol, it was possible to reduce the MIC as well as the MBC of methicillin, oxacillin, penicillin G, and ampicillin against resistant staphylococci. The strongest effects were obtained with methicillin and oxacillin. All strains tested could be resensitized to these penicillins independent of the original resistance levels. Polidocanol was not inhibitory by itself for Staphylococcus aureus. Furthermore, it did not inhibit the activity of staphylococcal beta-lactamase. This permits the conclusion that an intrinsic resistance mechanism is affected by this substance. Its action cannot be simply explained by an improved accessibility of the penicillin targets as uptake, and binding of methicillin and penicillin G in resistant cells was not changed by polidocanol. On the other hand, the lysis induced by combinations of this substance with small amounts of a penicillin was antagonized by chloramphenicol. This suggests that autolytic enzymes are involved in the polidocanol effect and possibly in the intrinsic resistance mechanism itself. Before polidocanol can trigger lysis, the penicillin must act first in some way. As could be seen with a susceptible strain, the resulting lysis did not exceed that obtained with penicillins alone. Thus, polidocanol does not exhibit an independent lytic mechanism but obviously is able to substitute penicillins in their lytic action.
D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002701:Chloramphenicol / Q000494:pharmacology; D003902:Detergents / Q000494:pharmacology*; D006602:Hexosyltransferases; D008712:Methicillin / Q000494:pharmacology; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D010068:Oxacillin / Q000494:pharmacology; D010400:Penicillin G / Q000494:pharmacology; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology*; D010458:Peptidyl Transferases; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects* / Q000201:enzymology; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D065093:beta-Lactamase Inhibitors
D001426:Bacterial Proteins; D002352:Carrier Proteins; D003902:Detergents; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D013501:Surface-Active Agents; D065093:beta-Lactamase Inhibitors; D000077423:Polidocanol; D011092:Polyethylene Glycols; D002701:Chloramphenicol; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G; D008712:Methicillin; D010068:Oxacillin