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Suppression of intrinsic resistance to penicillins in Staphylococcus aureus by polidocanol, a dodecyl
Abstract:
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.
Insights
Polidocanol resensitizes resistant Staphylococcus strains to penicillins like methicillin by affecting intrinsic resistance mechanisms. This non-inhibitory substance enhances penicillin
Area of Science:
- Microbiology
- Pharmacology
Background:
- Antibiotic resistance in Staphylococcus strains poses a significant clinical challenge.
- Developing novel strategies to overcome existing antibiotic resistance mechanisms is crucial.
Purpose of the Study:
- To investigate the effect of polidocanol on antibiotic resistance in Staphylococcus strains.
- To elucidate the mechanism by which polidocanol resensitizes bacteria to penicillin.
Main Methods:
- Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays were performed.
- Resensitization of resistant strains to various penicillins was tested.
- Bacterial uptake, binding, beta-lactamase activity, and lysis induction were analyzed.
Main Results:
- Polidocanol reduced the MIC and MBC of methicillin, oxacillin, penicillin G, and ampicillin against resistant staphylococci.
- All tested strains were resensitized to methicillin and oxacillin, irrespective of initial resistance levels.
- Polidocanol alone did not inhibit Staphylococcus aureus or its beta-lactamase activity, suggesting an intrinsic resistance mechanism is targeted.
Conclusions:
- Polidocanol resensitizes resistant staphylococci to penicillins by interfering with an intrinsic resistance mechanism, not by improving drug accessibility.
- The observed lysis, induced by polidocanol-penicillin combinations, is antagonized by chloramphenicol, indicating the involvement of autolytic enzymes.
- Polidocanol substitutes for penicillin's lytic action but does not possess an independent lytic mechanism.