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Paradoxical response of Enterococcus faecalis to the bactericidal activity of penicillin is associated with reduced
R Fontana1, M Boaretti, A Grossato
1Institute of Microbiology, University of Verona, Italy.
Abstract:
Ten clinical isolates of Enterococcus faecalis were examined for susceptibility to the bactericidal activity of penicillin. Four of these had MBCs of penicillin equal to 2 to 4 x the MIC, and six exhibited a paradoxical response to penicillin, i.e., the bactericidal activity of the antibiotic had a concentration optimum at 2 to 4 x the MIC and decreased significantly at concentrations above this. We found that the paradoxical response to penicillin was an intrinsic and stable property of a strain, but that its phenotypic expression was not homogeneous; only a fraction of the cell population that died at low concentrations was able to survive at high penicillin concentrations. The size of this fraction increased with increasing antibiotic concentration and reached a maximum in the late-log phase of growth. All 10 strains produced a lytic enzyme that was active on Micrococcus luteus heat-killed cells, whereas only some strains lysed E. faecalis heat-killed cells. Strains producing large amounts of the latter enzyme did not show the paradoxical response to penicillin, whereas mutants of these strains that lacked this enzymatic activity paradoxically responded to the antibiotic activity. In addition, from strains that showed paradoxical response to penicillin and produced only the enzyme that was active on M. luteus, it was possible to isolate mutants that were also capable of lysing E. faecalis cells and that were killed with similar efficiency by all concentrations above the MBC. On the basis of these findings, the paradoxical response to penicillin is explained as a property of certain strains of E. faecalis; this property is genetically characterized by alterations in synthesis or activity of one autolysin but phenotypically expressed only by a few cells that are in a particular physiological condition when exposed to high concentrations of antibiotics.
Insights
Certain Enterococcus faecalis strains show a paradoxical response to penicillin, where high concentrations are less effective. This phenomenon is linked to autolysin activity and specific cell growth phases, impacting antibiotic efficacy.
Area of Science:
- Microbiology
- Bacteriology
- Antibiotic Resistance
Background:
- Penicillin is a key antibiotic for treating Enterococcus faecalis infections.
- Understanding bacterial responses to antibiotics is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the paradoxical response of Enterococcus faecalis to penicillin's bactericidal activity.
- To elucidate the underlying mechanisms, including the role of lytic enzymes and cell physiology.
Main Methods:
- Assessed penicillin Minimum Bactericidal Concentrations (MBCs) and Minimum Inhibitory Concentrations (MICs) for ten clinical isolates.
- Examined the activity of lytic enzymes on heat-killed cells (Micrococcus luteus and E. faecalis).
- Isolated and analyzed mutants to understand the genetic and phenotypic basis of the paradoxical response.
Main Results:
- Six of ten E. faecalis strains exhibited a paradoxical response to penicillin, with reduced efficacy at high concentrations.
- The paradoxical response was an intrinsic strain property, influenced by cell growth phase and autolysin activity.
- Strains producing high levels of E. faecalis-lysing enzyme did not show the paradoxical response, while mutants lacking it did.
Conclusions:
- The paradoxical response in E. faecalis is linked to alterations in autolysin synthesis or activity.
- Phenotypic expression is heterogeneous, with a subpopulation surviving high penicillin concentrations.
- This finding has implications for optimizing penicillin therapy against E. faecalis infections.