Multi-resistant pathogens: This antibiotic comes from ourselves

Whether in the stable or in the clinic: multi-resistant germs threaten health. Researchers are looking for solutions – and have found a solution in the human body.

Multi-resistant pathogens: This antibiotic comes from ourselves

In order to kill pathogens, our immune, skin and mucosal cells, in a sense, release body-own antibiotics. These so-called antimicrobial peptides are highly effective against various germs. However, since y are also very unstable, y are not suitable for rapeutic use in ir natural form. Now Dutch researchers have changed one of se ingredients so that it is sufficiently stable for treatment of stubborn skin infections. Even multi-resistant bacteria and those protected by a biofilm were very effectively killed by new substance. Anor advantage is that bacteria have not developed resistance, even for prolonged use, as Doctors report in journal Science Translational Medicine (de Breij et al. 2018). A clinical trial will be started later this year.

"The peptide SAAP-148 has a broad spectrum of activities against multi-resistant bacteria, persistent forms of rest of bacteria and biofilms that cause difficult-to-treat infections," writes Anna de Breij from Medical Center of Leiden University and Your colleagues. Multi-resistant germs have evolved through mutation mechanisms that make a variety of antibiotics ineffective. In or ways, bacteria are protected within biofilms, a self-produced mucus layer. In addition, individual bacteria can enter a hibernation state and become persister cells. Then y are no longer vulnerable to such antibiotics, which are effective only in active cells. These different protection mechanisms of bacteria are causes of chronic or recurring infections.

Antimicrobial peptides consist of a chain of amino acids. They unfold ir effect by making cell membrane of bacteria holes. In order to develop an antibiotic-effective drug from such a peptide, it must be chemically modified in such a way that it remains stable in blood, in wound fluid or in urine. The starting point for search for such a "syntic antimicrobial anti-biofilm-peptide" (SAAP) was peptide LL-37, formed by human immune cells, from group of Calicidine. The researchers shortened molecule consisting of 37 amino acids to only 24 components and exchanged some of m against or amino acids, so that positive charge of molecular chain increased.

Active ingredient to be used soon

Of a total of 25 tested peptides, SAAP-148 proved to be particularly promising. It was in laboratory experiments – also in presence of blood serum – effective against multiresistant staph and Enterococci as well as various clinically significant stick bacteria, including Acinetobacter and pseudo-monad. Even after prolonged cultivation with low concentrations of SAAP-148, no bacterial strains resistant to peptides could be exhibited. In laboratory culture, peptide also killed Staphylococcus aureus and Acinetobacter in biofilms and was effective against Staphylococcus's persister cells. Finally, researchers treated a tissue culture of infected human skin with a gel that was added to SAAP-148. After four hours, multidrug-resistant staph (MRSA) or Acinetobacter bacteria were completely eliminated. There was no discernible damage to skin cells. The treatment of experimentally infected abrasions of mice yielded similar results.

The scientists hope to be able to use ir new active ingredient soon for local treatment of persistent skin infections – including infected burns and diabetic ulcers. A first clinical study is planned for beginning of this year. Before an application for treatment of infections in body, it is necessary to develop a suitable form of administration, for example with aid of special active ingredient capsules.

Date Of Update: 12 January 2018, 12:03
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