A New Therapy to Combat Drug-Resistant Bacteria

Antibiotics, also referred to as antimicrobial drugs, are one of the most frequently used drugs in medicine. They treat bacterial infections by either killing the bacteria or preventing the bacteria from reproducing and spreading. The emergence of drug-resistant bacteria has reduced the effectiveness of antibiotics. It is projected that approximately 10 million people will die by the year 2050 due to drug-resistant bacteria. Therefore, it is extremely important that new methods are produced to successfully treat bacteria that has adapted over time to resist antibiotics. The researchers suggest that antimicrobial peptides (AMPs) could be a good substitute for current antibiotics. These peptides are present in all living organisms and help defend against microbial infections. Approximately half of the amino acids present in AMPs are hydrophobic, but can adopt amphipathic structures (molecules containing hydrophobic and hydrophilic regions), which allows them to penetrate cell membranes. Franco et. al generated a synthetic peptide known as clavanin-MO. A marine tunicate antimicrobial peptide was used to derive this synthetic peptide.

            Their experiments, which were performed in vitro and in vivo, showed that clavanin-MO contained antimicrobial and immunomodulatory properties. The peptide was successfully active against all the bacterial strains that were tested. Additionally, its efficacy for killing gram-negative and gram-positive bacteria was investigated, and it produced more successful results than the human cathelicidin AMP-LL37. The effectiveness of the peptide was also compared to two commonly used antibiotics, gentamicin and imipenem. Clavinin-MO proved to be more effective, even for multidrug resistant E. coli 2101123. These results exhibit clavanin-MO’s ability to treat a wide range of infections.

            The researchers also performed studies in vitro and in vivo to assess the toxic effects of clavanin-MO. Mouse red blood cells (mRBCs), RAW264.7 macrophage, L929 mouse fibroblast cell lines, and human embryonic kidney cells 293 (HEK-293) were used to perform the experiments. Concentrations of clavanin-MO necessary to produce antimicrobial activity were introduced to RAW264.7, L929 cells, and HEK-293 cells, and no cytotoxic effects were observed. A dose five times the amount necessary for successful antimicrobial treatment was administered to the mice, and still no toxicity was observed. Side effects must be considered when creating new treatments. It is very encouraging that such a large dose did not produce toxic effects. This demonstrates that the treatment can be not only effective, but also safe, which is just as important.

            Clavanin-MO was also found to contain beneficial immunomodulatory properties. One experiment was performed in vivo using the mice to track the migration of leukocytes to the infected area. A major component of treating infections involves inducing leukocytes to travel to the area of infection. Some peptides are able to perform this immunomodulatory activity. The results showed that clavanin-MO significantly increased the number of leukocytes present in the infected area of the mice.

            The increase in antibiotic-resistant bacteria coupled with the lack of antimicrobial therapy development has caused an urgency to create alternative treatments for bacterial infections. Franco et. al have introduced a possible alternative that is very promising. A single peptide, clavanin-MO, has the ability to kill bacteria directly, but can also stimulate immune cells to attack the host. Additionally, throughout the treatment process, the peptide failed to produce toxic effects. While more research is needed, this new therapy moves us considerably closer to a method that combats the rise of antibiotic-resistant bacteria.

References:

http://www.nature.com/articles/srep35465

http://www.cdc.gov/drugresistance/index.html