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Cyclic dominant negative competence stimulating peptide analogs to treat Streptococcus pneumoniae infections

Description:

Background

Streptococcus pneumoniae (pneumococcus) is a bacterial pathogen responsible for many diseases in humans including pneumonia, meningitis, sepsis, and otitis media. It is a prevalent source of health and economic burden, with a death toll of >22,000 a year and >$3.5 billion in direct medical costs in the US alone. Concerns for current S. pneumoniae treatment methods arises in the development of antibiotic resistant and vaccine-escape strains. This is due to its highly recombinogenic nature and ability to rapidly acquire new genetic materials from the environment through activation of its competence regulon. Additionally, the currently prescribed 4th-generation fluoroquinolone antibiotics have been reported to activate the competence regulon, which may exacerbate the negative side effects of these essential antibacterials.

 

Description

Researchers at University of Nevada, Reno and University of Illinois at Urbana-Champaign have invented a novel method for treating S. pneumoniae infections, focused on targeting the competence regulon, a quorum sensing circuitry that regulates virulence in S. pneumoniae. To this end, they have designed and developed cyclic peptide scaffolds that mimic the native competence stimulating peptide (CSP) pheromone. These dominant negative competence stimulating peptides (dnCSPs) inhibit the quorum sensing circuitry and attenuate S. pneumoniae virulence. In vitro use of dnCSPs decrease pneumococcal virulence by inhibiting the release of pneumolysin toxin. In vivo mouse studies demonstrate that dnCSPs effectively attenuate acute lung infections, with evidence for a pan-dnCSP that cover the majority of pneumococcal strains. Because quorum sensing is not essential for bacterial growth, the use of a dnCSPs will reduce virulence and improve lung conditions, with minimal selective pressures for the development of resistant pneumococcal strains.

 

Advantages

  1. Novel treatment method using dnCSPs to inhibit quorum sensing
  2. Non-antibiotic treatment method
  3. Treatment of antibiotic resistant pneumococcus infections
  4. Alleviate adverse side-effects of currently used pneumococcal antibiotics
  5. Reducing selective pressures and the likelihood of developing antibiotic resistance
  6. dnCSPs are effective against the majority of S. pneumoniae strains

Related Links

 

UNR19-015

Patent Information:
For Information, Contact:
Cara Baird
Licensing Associate
University of Nevada, Reno
carab@unr.edu
Inventors:
Keywords: