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Penicillin tolerance in multiply drug-resistant natural isolates of Streptococcus pneumoniae
Abstract:
Five of six multiply drug-resistant clinical isolates of Streptococcus pneumoniae from South Africa demonstrated penicillin tolerance. In contrast to the common wild-type strains of pneumococci, treatment of the tolerant strains with penicillin above the minimum inhibitory concentration did not induce cell wall degradation, lysis, or leakage of intracellular components, and the rate of loss of viability was reduced compared with that of nontolerant strains. While these South African strains contained lower specific activity of autolytic enzyme than did nontolerant strains, the residual autolytic activity (15%-26% of the nontolerant wild type) was much more than that found in lysis-defective laboratory mutants of pneumococci (less than or equal to 1%); the rate of penicillin-induced lysis did not correlate with the specific activity of residual autolysin. Also, in contrast to the complete lysis resistance of lysis-defective mutants to all lytic agents, the tolerant South African strains were resistant primarily to lysis by beta-lactam antibiotics but could still be lysed by other cell wall inhibitors (e.g., cycloserine) and detergents. The penicillin resistance and penicillin tolerance traits could be separated by genetic transformation. We suggest that the drug-specific tolerance of the South African pneumococcal strains is related to some alteration in the control of autolysin activity.
Insights
South African Streptococcus pneumoniae strains exhibit drug-specific penicillin tolerance, not complete lysis resistance. This tolerance, linked to altered autolysin activity control, impacts antibiotic treatment strategies.
Area of Science:
- Microbiology
- Molecular Biology
- Pharmacology
Background:
- Multiply drug-resistant Streptococcus pneumoniae (pneumococci) pose a significant public health challenge.
- Penicillin tolerance, distinct from resistance, affects bacterial response to antibiotic treatment.
- Clinical isolates from South Africa revealed unique resistance and tolerance profiles.
Purpose of the Study:
- To investigate the characteristics of penicillin tolerance in drug-resistant Streptococcus pneumoniae clinical isolates from South Africa.
- To differentiate tolerance mechanisms from complete lysis resistance observed in laboratory mutants.
- To explore the role of autolytic enzyme activity in penicillin tolerance.
Main Methods:
- Phenotypic characterization of clinical pneumococcal isolates regarding drug resistance and tolerance.
- Assessment of cell wall degradation, lysis, and viability loss upon penicillin treatment.
- Measurement of autolytic enzyme specific activity and correlation with lysis rates.
- Genetic transformation experiments to separate resistance and tolerance traits.
Main Results:
- Five of six multiply drug-resistant isolates demonstrated penicillin tolerance.
- Tolerant strains showed reduced cell wall degradation, lysis, and viability loss with penicillin.
- Autolytic enzyme activity was lower but residual activity was higher than in lysis-defective mutants.
- Tolerance was specific to beta-lactam antibiotics, with sensitivity to other lysis agents.
Conclusions:
- Drug-specific penicillin tolerance in South African pneumococcal strains is likely due to altered autolysin activity control.
- Tolerance mechanisms differ from complete lysis resistance seen in laboratory mutants.
- Understanding these mechanisms is crucial for optimizing antibiotic therapy for resistant pneumococcal infections.