New broad-spectrum antibiotic did not cause resistance in bacteria

Scientists have discovered a new antibacterial substance active against gram-positive and gram-negative bacteria and does not cause resistance. As stated in the article, published in the journal Cell, the substance acts directly on two targets: on the metabolism of folate and on the cell membrane of bacteria. Due to the dual mechanism of action, bacteria could develop resistance to the new substance.

Over the last 20 years for practical use in medicine had been approved only six new classes of antimicrobials, and none of them are active against gram-negative bacteria. For comparison, during the first 30 years after the discovery of penicillin in 1929 was described and introduced in practice more than twenty classes of antibiotics. Such a sharp decline in the rate of development of new antimicrobial agents is often attributed to economic factors, because the creation of such a drug is expensive and takes a lot of time and clinical trials it may not pass.

Therefore, pharmaceutical companies rarely take risks, because of what the world has created a public health crisis: the evolution of multi-resistant bacteria, horizontal transfer of resistance genes between bacteria, coupled with old and no longer existing drugs — all this has led to the emergence of bacteria that are not operates virtually none of the currently known antibiotic. The brightest representative of this cohort — methicillinresistant Staphylococcus aureus, or MRSA. In our big article “the End of a great era” we talked about the main problems faced by doctors around the world, trying to cure infections caused by antibiotic-resistant bacteria, and how did it happen that the descendants who saved once millions of people penicillin can’t help us today.

The issue of treatment-resistant bacterial infections every year becomes more acute. With this aim modify old antibiotics used analogs of vitamin A, but may completely solve the problem of creation of new classes of antibiotics that do not cause resistance in microorganisms.

A group of scientists under the leadership of James Martin, II (James K. Martin II) from Princeton University were in search of broad-spectrum antibiotics with novel mechanisms of action on bacterial cells. The study was performed in E. coli, devoid of lipopolysaccharide. 33000 unique among molecules, scientists drew attention to the one — SCH-79797. It is an antagonist of the receptor-activated protease, the first type, which is found on platelets, immune cells, skin cells and many other cells. Receptors in this class are involved in the regulation of hemostasis and inflammation. The very same SCH-79797 increases the ability of neutrophils to kill bacteria, acting possibly as an antibiotic. Given that studieson its anticoagulant activity, showed that at least five milligrams SCH-79797 per kilogram of body weight can safely be carried in animals, the researchers decided to investigate how this substance kills bacteria.

When culture study revealed that SCH-79797 inhibits the growth of gram-negative bacteria Neisseria gonorrhoeae and Acinetobacter baumannii, and gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus. Including decreased growth of colonies of multi-resistant strains of N. gonorrhoeae and MRSA.

The study in vivo on the larvae of wax moth infected with a lethal dose of A. baumannii, showed low toxicity substances: the larvae were injected four times of the minimum inhibitory concentration of SCH-79797, and it did not cause significant changes of life. While the survival of larvae significantly increased (p < 0.001).

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