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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Streptococcus pyogenes genes that promote pharyngitis in primates.

Luchang Zhu1, Randall J Olsen1,2, Stephen B Beres1

  • 1Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist Research Institute, and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.

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Researchers identified 115 key genes and potential vaccine targets for Streptococcus pyogenes (group A Streptococcus; GAS) pharyngitis by studying nonhuman primates. This advances understanding of GAS upper respiratory tract colonization and disease.

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Area of Science:

  • Microbiology
  • Immunology
  • Vaccinology

Background:

  • Streptococcus pyogenes (group A Streptococcus; GAS) causes significant global pharyngitis burden.
  • No licensed human GAS vaccine exists despite extensive research.
  • GAS upper respiratory tract colonization and pathogenesis mechanisms remain poorly understood.

Purpose of the Study:

  • To identify novel GAS fitness genes and virulence factors crucial for pharyngitis.
  • To discover potential vaccine targets for GAS infection.
  • To elucidate molecular processes underlying GAS colonization and persistence in the oropharynx.

Main Methods:

  • Genome-wide screens using dense transposon mutant libraries and transposon-directed insertion sequencing (Tn-seq) in a nonhuman primate (NHP) oropharyngeal model.
  • Identification of GAS fitness genes common to both M1 and M28 serotypes.
  • Targeted gene deletion to validate identified virulence factors.

Main Results:

  • Identified a common set of 115 GAS fitness genes essential for virulence in both M1 and M28 strains during experimental NHP pharyngitis.
  • Confirmed the critical role of four newly identified fitness genes/operons in GAS virulence.
  • Discovered several surface-exposed or secreted proteins, including lipoprotein HitA, as potential vaccine substrates.
  • Demonstrated that pooled human immune globulin reacts with HitA, indicating human antibody response.

Conclusions:

  • This study provides novel insights into GAS fitness and virulence in the upper respiratory tract.
  • Identified potential vaccine candidates, such as HitA, for developing a human GAS vaccine.
  • Findings support translational research for novel GAS vaccines and therapeutic strategies.