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Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae

J P Maskell1, A M Sefton, L M Hall

  • 1Department of Medical Microbiology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom. J.Maskell@mds.qmw.ac.uk

Antimicrobial Agents and Chemotherapy
|October 23, 1997
PubMed

Insights

Sulfonamide resistance in Streptococcus pneumoniae is caused by duplications in the sulA gene. These genetic changes, confirmed through DNA transformation experiments, lead to amino acid alterations and confer resistance.

Area of Science:

  • Microbiology
  • Genetics
  • Antimicrobial Resistance

Background:

  • Sulfonamides are crucial antibiotics, and resistance in Streptococcus pneumoniae poses a significant public health threat.
  • Understanding the genetic mechanisms of sulfonamide resistance is vital for developing effective treatment strategies.

Purpose of the Study:

  • To elucidate the genetic basis of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae.
  • To confirm the role of specific genetic alterations in conferring resistance.

Main Methods:

  • Analysis of the sulA gene in six resistant and six susceptible clinical isolates of Streptococcus pneumoniae.
  • Polymerase chain reaction (PCR) amplification and sequencing of sulA gene fragments.
  • Confirmation of resistance mechanism via DNA transformation experiments.

Main Results:

  • Three- or 6-bp duplications within the sulA gene were identified in all six resistant isolates.
  • These duplications resulted in amino acid repetitions within a specific region of the dihydropteroate synthase enzyme.
  • Sulfonamide-susceptible isolates lacked these duplications, and transformation experiments confirmed their role in resistance.
  • Analysis of a serotype 9V clone suggested potential horizontal gene exchange, while distinct mutations in other isolates indicated independent origins of resistance.

Conclusions:

  • Duplications in the sulA gene are the primary genetic cause of sulfonamide resistance in these clinical Streptococcus pneumoniae isolates.
  • The findings highlight the diverse evolutionary pathways leading to antimicrobial resistance, including independent mutations and potential horizontal gene transfer.

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