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Sensitivity of Pseudomonas aeruginosa envelope mutants to alkylbenzyldimethylammonium chlorides
Abstract:
A series of stepwise polymyxin-resistant envelope mutants of Pseudomonas aeruginosa was used to test the activity of a homologous series (C10-C18) of alkylbenzyldimethylammonium chlorides. A sterilization kinetics procedure in deionized water was devised to avoid amounts quaternary compound above the critical micelle concentration. In all cases, there was a linear relationship between the logarithm of the rate of change of the colony count with time and the logarithm of the homolog concentration. For all strains, there was a linear relationship between alkyl chain length and the concentration required to reduce the colony count to 10% in 2 hr. The stepwise series of polymyxin-resistant strains increased in resistance to polymyxin about threefold for each step. In general, this increase resulted in a similar increase in resistance to the quaternary compound. It is proposed that death in this system may primarily be a consequence of damage to the outer membrane rather than to the cytoplasmic membrane.
Insights
Pseudomonas aeruginosa mutants resistant to polymyxin also showed increased resistance to quaternary ammonium compounds. This suggests outer membrane damage is key to bacterial death from these agents.
Area of Science:
- Microbiology
- Bacteriology
- Antimicrobial Resistance
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic resistance to many antimicrobial agents.
- Polymyxins are last-resort antibiotics, and resistance is a growing concern.
- Quaternary ammonium compounds are widely used disinfectants and antiseptics.
Purpose of the Study:
- To investigate the relationship between polymyxin resistance and susceptibility to a homologous series of alkylbenzyldimethylammonium chlorides in Pseudomonas aeruginosa.
- To determine the influence of alkyl chain length on the antimicrobial activity of these quaternary compounds.
- To elucidate the potential mechanism of cell death induced by quaternary ammonium compounds.
Main Methods:
- Utilized stepwise polymyxin-resistant envelope mutants of Pseudomonas aeruginosa.
- Employed a sterilization kinetics procedure in deionized water to control quaternary compound concentration below the critical micelle concentration.
- Quantified bacterial killing rates and determined concentrations for a 90% reduction in colony count over 2 hours.
Main Results:
- Demonstrated a linear correlation between the logarithm of the killing rate and the logarithm of the quaternary compound concentration.
- Established a linear relationship between alkyl chain length and the concentration required to achieve 90% bacterial reduction.
- Observed that increased polymyxin resistance (approximately threefold per step) correlated with a similar increase in resistance to the quaternary compounds.
Conclusions:
- Bacterial resistance to polymyxins is associated with cross-resistance to certain quaternary ammonium compounds.
- Antimicrobial activity of alkylbenzyldimethylammonium chlorides is influenced by both bacterial resistance mechanisms and alkyl chain length.
- Bacterial death induced by these quaternary compounds likely results primarily from damage to the outer membrane, not the cytoplasmic membrane.
