Heterogeneous macrolide resistance and gene conversion in the pneumococcus

Area of Science:

• Microbiology
• Molecular Biology
• Antimicrobial Resistance

Background:

• Macrolide antibiotics are crucial for treating Streptococcus pneumoniae infections.
• Emergence of antibiotic resistance, particularly macrolide resistance, poses a significant public health threat.
• Understanding the genetic and phenotypic basis of macrolide resistance in pneumococci is essential for effective treatment strategies.

Purpose of the Study:

• To investigate the genetic and phenotypic characteristics of a macrolide-resistant clinical isolate of Streptococcus pneumoniae.
• To determine the mechanism underlying the heterogeneous expression of macrolide resistance.
• To elucidate the stability of macrolide resistance in the absence of antibiotic pressure.

Main Methods:

• Characterization of a clinical Streptococcus pneumoniae isolate exhibiting macrolide resistance.
• Genetic transformation experiments using mutant 23S rRNA genes.
• Culturing of resistant strains under non-selective conditions to observe phenotypic changes.
• Analysis of gene conversion events between 23S rRNA alleles.

Main Results:

• A clinical isolate of Streptococcus pneumoniae with 23S rRNA mutations displayed heterogeneous macrolide resistance.
• Introduction of mutant 23S rRNA genes conferred resistance to a susceptible strain (R6).
• In the absence of antibiotic pressure, gene conversion between 23S rRNA alleles led to reversion to susceptibility.
• The resistant phenotype was associated with a fitness cost, explaining its instability.

Conclusions:

• Heterogeneous macrolide resistance in Streptococcus pneumoniae is linked to specific 23S rRNA mutations.
• Gene conversion mechanisms contribute to the loss of resistance upon prolonged culturing without antibiotics.
• The fitness cost associated with resistance can drive the reversion to susceptibility, impacting resistance prevalence.