Bacterial Abscess Formation Is Controlled by the Stringent Stress Response and Can Be Targeted Therapeutically

Sarah C. Mansour, Daniel Pletzer, César de la Fuente-Núñez, Paul Kim, Gordon Y.C. Cheung, Hwang Soo Joo, Michael Otto, Robert E.W. Hancock

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cutaneous abscess infections are difficult to treat with current therapies and alternatives to conventional antibiotics are needed. Understanding the regulatory mechanisms that govern abscess pathology should reveal therapeutic interventions for these recalcitrant infections. Here we demonstrated that the stringent stress response employed by bacteria to cope and adapt to environmental stressors was essential for the formation of lesions, but not bacterial growth, in a methicillin resistant Staphylococcus aureus (MRSA) cutaneous abscess mouse model. To pharmacologically confirm the role of the stringent response in abscess formation, a cationic peptide that causes rapid degradation of the stringent response mediator, guanosine tetraphosphate (ppGpp), was employed. The therapeutic application of this peptide strongly inhibited lesion formation in mice infected with Gram-positive MRSA and Gram-negative Pseudomonas aeruginosa. Overall, we provide insights into the mechanisms governing abscess formation and a paradigm for treating multidrug resistant cutaneous abscesses.

Original languageEnglish
Pages (from-to)219-226
Number of pages8
JournalEBioMedicine
Volume12
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

Keywords

  • Cationic peptide
  • DJK-5
  • Pseudomonas aeruginosa
  • Staphylococcus aureus
  • ppGpp

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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