Synthetic peptides to target the stringent stress response as potential new therapeutic approach
There has been enormous publicity about the inexorable rise of antibiotic resistance and the lack of new therapies. However, less attention has been placed on multidrug-resistant biofilm or high-density infections for which antibiotics are highly used but no effective therapies currently exist. Here we show how synthetic peptides can be used as an adjuvant therapy to target bacterial infections in a cutaneous mouse model of chronic infection. Synthetic peptides interact with the stringent stress response and promote the hydrolysis of the nucleotide signaling molecule GDP,3’-diphosphate (ppGpp). Pharmacokinetics showed that the peptide remained within the host tissue for several hours to days depending on the route of administration. We further explored the potential of synthetic peptides to target motility in Pseudomonas aeruginosa and show how this could be used to interfere with dissemination and colonization in an acute infection model. Since these peptides have the potential to broaden our limited antibiotic arsenal for extremely difficult to treat infections, we investigated the mechanisms of stringent stress regulation under relatively unstressed conditions. Overall, this expands our knowledge about the stringent stress response and provides information about the consequences of targeting this ubiquitous bacterial signaling molecule.
|Date||Tuesday, 29 September 2020|
|Time||12:00pm - 1:00pm|
|Event Category||Health Sciences|
|Location||Biochemistry Seminar Room G13|
University of Otago
|Contact Name||The Department of Biochemistry|