New peptide prevents infection during treatment with urinary catheter
Utilizing a synthetic peptide developed at Uppsala University, researchers at KI have identified an alternative method to prevent and treat infection during care with urinary catheters. "If we reach clinic, this can generate great benefit for both patients and healthcare," states Ulf Göransson, Professor of Pharmacognosy.
(Image removed) Ulf Göransson, Professor, The Faculty of Pharmacy
The antimicrobial peptide CD4-PP, developed at Ulf Göransson's research environment in pharmacognosy, shows in a current study bactericidal abilities against several of the bacteria that cause urinary tract infections. Now, researchers hope that the peptide will provide a basis for an alternative treatment to reduce the risk of infection for patients with urinary catheters.
“Treatment with an indwelling catheter through the urethra is associated with a greatly increased risk of contracting bacterial infections, which can cause both difficult-to-treat and fatal disease. We have worked with the endogenous peptide LL-37, which controls several important functions during infectious diseases, and in particular the segment of LL-37 where its antimicrobial activity is concentrated. After some modifications, we succeeded in creating the more stable and potent CD4-PP, which attracted interest at Karolinska Institutet,” says Ulf Göransson, Professor of Pharmacognosy at Uppsala University.
(Image removed) Annelie Brauner, Karolinska Institutet
In the study, Annelie Brauner, Professor of Clinical Microbiology, concludes CD4-PP's effectiveness against the most common bacterial species that cause urinary tract infections, but also against antibiotic-resistant bacteria, which are very difficult to treat with ordinary antibiotics. This synthetically produced peptide is also active against biofilm, a form of mucus secreted by bacteria, which increases their resistance to both our immune system as well as various antibiotics.
“Our results show how the peptide dissolves existing biofilm, prevents the formation of new biofilm, and also activates the body's immune system in order to protect cells against infection. In addition, when we applied CD4-PP with a saline solution to the catheter, it prevented E. coli bacteria from attaching to its surface, which are all important steps in preventing infections,” states Annelie Brauner.
The development of CD4-PP was conducted within Taj Muhammad's PhD project at Uppsala University's Faculty of Pharmacy. By replacing certain amino acids and constructing a cyclically designed peptide, a stronger antimicrobial effect and an extended duration of action were achieved. Now, further studies await on how CD4-PP should be utilized to optimize the effect during catheter treatment. There are also hopes of applying the peptide against skin infections.
“The progress we have accomplished so far is the result of collaborations between different disciplines, including Natalia Ferraz's research team of material chemists here at Uppsala University. Together, we have good opportunities to reach significantly further. One obstacle is that the production of CD4-PP is both expensive and time-consuming. Therefore, Taj Muhammad is currently in Aberdeen to develop a more efficient production method. As soon as he succeeds, we will take another big step towards clinical treatment, which has obvious potential to be of great benefit to both patients and healthcare,” says Ulf Göransson.
FACTS
- Peptides and proteins are produced in all living organisms to fulfill important biological functions.
- The use of peptides and proteins in drug development is often prevented by their instability.
- Researchers at Uppsala University have shown that certain plants produce a cocktail of unusual polypeptides that are cyclized head-to-tail via amide bonds and exhibit exceptional chemical and biological stability.
LEARN MORE
- Research in Pharmacognosy at Uppsala University
- LL-37-derived cyclic antimicrobial drug leads: Design, synthesis, activity and different ways of creating them (Taj Muhammad, 2019)
- Read articleA stable cyclized antimicrobial peptide derived from LL‑37 with host immunomodulatory effects and activity against uropathogens (Cellular and Molecular Life Sciences, 11 July 2022)
CONTACT
(Image removed) Ulf Göransson, Professor
Department of Pharmaceutical Biosciences
Ulf.Goransson@farmbio.uu.se
text: Magnus Alsne, photo: Mikael Wallerstedt, Johannes Frandsen