Multiple mutations and increased RNA expression in tetracycline-resistant Streptococcus pneumoniae as determined by

Andréanne Lupien1, Hélène Gingras1, Michel G Bergeron1

  • 1Centre de recherche en Infectiologie du Centre de recherche du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada.

Abstract

Insights

Novel chromosomal mutations in Streptococcus pneumoniae confer resistance to tetracycline. These include alterations in rpsJ and ABC transporter genes (patA, patB), impacting drug accumulation and thiamine pathways.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Tetracycline resistance is a growing concern in bacterial infections.
  • Understanding the genetic basis of resistance is crucial for developing new treatment strategies.

Purpose of the Study:

  • To identify and characterize chromosomal mutations conferring tetracycline resistance in Streptococcus pneumoniae.
  • To elucidate the molecular mechanisms underlying this resistance.

Main Methods:

  • Next-generation sequencing (whole-genome and RNA sequencing) was employed to analyze resistant mutants.
  • Functional validation was performed by reconstructing resistance mutations in a wild-type S. pneumoniae background.

Main Results:

  • Mutations in rpsJ (ribosomal protein S10) and ABC transporter genes (patA, patB) were identified.
  • Overexpression of PatA/PatB or mutations in patA conferred cross-resistance to ciprofloxacin and ethidium bromide.
  • Increased expression of thiamine biosynthesis/salvage pathway genes was observed in resistant strains.

Conclusions:

  • Genomic and transcriptomic analyses revealed novel tetracycline resistance mutations in S. pneumoniae.
  • The identified mutations and associated gene expression changes provide new insights into tetracycline resistance mechanisms.

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