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Published on: June 5, 2012
High temperature induced antibiotic sensitivity changes in Pseudomonas aeruginosa
1Defence Research Establishment Suffield, Ralston, Alberta, Canada.
Abstract:
Pseudomonas aeruginosa, which was resistant to a wide variety of antibiotics, became sensitive to several of these antibiotics when grown and tested at 46 degrees C. Cell wall antibiotics such as penicillin G and ampicillin were only effective when added to cells growing at 46 degrees C prior to a temperature shift to 37 degrees C. Antibiotics which penetrate the cytoplasmic membrane to express their inhibiting action present a pattern different from those which are active against the outer cell wall. In order that these compounds be effective, the permeability of the cytoplasmic membrane must be further altered with agents such as EDTA which allow the penetration of actinomycin D. Inhibitors of protein synthesis, such as streptomycin and chloramphenicol, have increased access to their sites of action in cells grown at 46 degrees C. Cells grown at 46 degrees C have 40% less lipopolysaccharide (LPS) than cells grown at 37 degrees C and the LPS aggregates were of large molecular size in cells grown at 46 degrees C. Growth at 46 degrees C affects the permeability properties of the outer cell wall more than the permeability properties of the cytoplasmic membrane and this was due, in part, to the selective release of LPS of LPS-protein complexes at elevated growth temperatures.
Insights
Elevating growth temperature to 46°C re-sensitizes Pseudomonas aeruginosa to antibiotics by altering cell wall permeability. This temperature shift impacts lipopolysaccharide structure and release, enhancing antibiotic efficacy.
Area of Science:
- Microbiology
- Bacteriology
- Antibiotic Resistance
Background:
- Pseudomonas aeruginosa exhibits resistance to numerous antibiotics.
- Understanding mechanisms of antibiotic resistance is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effect of elevated growth temperature (46°C) on the sensitivity of Pseudomonas aeruginosa to various antibiotics.
- To elucidate the impact of temperature on bacterial cell wall and membrane permeability.
Main Methods:
- Culturing Pseudomonas aeruginosa at 46°C and 37°C.
- Testing antibiotic susceptibility at different temperatures.
- Analyzing cell wall composition, specifically lipopolysaccharide (LPS) content and aggregation.
- Assessing the role of EDTA in enhancing antibiotic penetration.
Main Results:
- Pseudomonas aeruginosa grown at 46°C showed increased sensitivity to several antibiotics.
- Cell wall-acting antibiotics required pre-incubation at 46°C before temperature shift.
- Elevated temperature reduced lipopolysaccharide (LPS) content by 40% and altered LPS aggregation.
- Growth at 46°C increased permeability of the outer cell wall, partly due to LPS release.
Conclusions:
- Increased growth temperature (46°C) can restore antibiotic sensitivity in Pseudomonas aeruginosa.
- Temperature-dependent alterations in the outer cell wall, particularly LPS structure and release, are key to this phenomenon.
- Targeting cell wall permeability offers a potential strategy to overcome antibiotic resistance.
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