Identification and prioritization of macrolideresistance genes with hypothetical annotation inStreptococcus

Blue Goad1, Laura K Harris1

  • 1Davenport University, 200 S. Grand Ave, Lansing, MI, 48933, USA.

Bioinformation
|June 22, 2019
PubMed

Insights

Identifying novel macrolide resistance genes in Streptococcus pneumoniae is crucial. This study highlights hypothetical genes and domains of unknown function (DUFs) that could lead to new therapies against resistant bacterial infections.

Area of Science:

  • Microbiology
  • Genomics
  • Drug Discovery

Background:

  • Macrolide-resistant Streptococcus pneumoniae poses a significant treatment challenge.
  • Incomplete genome annotation, including hypothetical genes encoding domains of unknown function (DUFs), hinders understanding of resistance mechanisms.

Purpose of the Study:

  • To identify and confirm macrolide resistance genes in Streptococcus pneumoniae.
  • To explore DUFs within hypothetical macrolide resistance genes for prioritizing experimental characterization.

Main Methods:

  • Comparative analysis of gene expression signatures between untreated and macrolide-treated resistant Streptococcus pneumoniae strains.
  • Validation using independent datasets of resistant and sensitive Streptococcus pneumoniae strains.
  • Functional pathway analysis of identified resistance genes.

Main Results:

  • Identified gene similarities associated with macrolide resistance.
  • Confirmed gene sets linked to resistance mechanisms like increased amino acid biosynthesis and efflux, and decreased ribonucleotide biosynthesis.
  • Discovered 22 hypothetical genes, including 10 DUFs, associated with macrolide resistance.

Conclusions:

  • Characterizing DUFs in macrolide resistance genes may reveal novel co-therapies to restore macrolide efficacy.
  • The applied methodology shows predictive power and can be extended to other antibiotic resistance mechanisms.
  • This research could revolutionize the treatment of resistant bacterial infections.

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