Differences in potential for selection of clindamycin-resistant mutants between inducible erm(A) and erm(C)

Claire Daurel1, Corinne Huet, Anne Dhalluin

  • 1Service de Microbiologie, CHU Côte de Nacre, 14033 Caen cedex, France.

Insights

The erm(C) gene in Staphylococcus aureus leads to a significantly higher mutation rate for clindamycin resistance compared to the erm(A) gene. This finding is crucial for understanding antibiotic resistance development in staphylococci.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Inducible macrolide-lincosamide-streptogramin B (MLS(B)) resistance in staphylococci is often mediated by erm(C) or erm(A) genes.
  • The D-zone test is used to identify this inducible resistance phenotype.
  • Clindamycin resistance can emerge in Staphylococcus aureus with inducible MLS(B) resistance, even when clindamycin appears effective in vitro.

Purpose of the Study:

  • To compare the frequencies of mutation to clindamycin resistance in Staphylococcus aureus isolates carrying erm(C) versus erm(A) genes.
  • To investigate the genetic potential of erm(C) and erm(A) in selecting for clindamycin-resistant mutants.

Main Methods:

  • Mutation frequency analysis for clindamycin resistance in 28 S. aureus isolates with inducible MLS(B) resistance (18 erm(C), 10 erm(A)).
  • Inclusion of control isolates with erythromycin susceptibility or msr(A) gene (efflux).
  • Cloning of erm(C) and erm(A) genes into S. aureus RN4220 to assess gene-specific effects.

Main Results:

  • Isolates with the erm(C) gene showed a 14-fold higher mean mutation frequency to clindamycin resistance (4.7 x 10(-7)) compared to isolates with the erm(A) gene (3.4 x 10(-8)).
  • Mutation frequencies for erm(A) isolates were only slightly higher than for control isolates (1.1 x 10(-8)).
  • The difference in mutation frequency between erm(C) and erm(A) was also observed when genes were cloned into S. aureus RN4220.

Conclusions:

  • The erm(C) and erm(A) genes possess distinct genetic potentials for selecting clindamycin-resistant mutants in S. aureus.
  • Distinguishing between erm(C) and erm(A) may be possible using the disk diffusion test based on high- versus low-level resistance to oleandomycin.

Related Concept Videos

Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Antibiotic Selection00:57

Antibiotic Selection

Overview
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...