15 January 2021

Formicamycin against MRSA

GM bacteria have been taught to produce ten times more antibiotic against Staphylococcus

Vasily Parfenov, Naked Science

In the war of mankind against pathogenic bacteria, people are rapidly losing the initiative: microbes are adapting better to the effects of antibiotics. The recognized champion in this discipline is methicillin–resistant Staphylococcus aureus (MRSA). This infection is extremely difficult to suppress by known methods, and if the patient's immune system is weakened, MRSA can provide a whole range of severe complications in the shortest possible time.

staphylococcus.jpg

A photo of a biofilm of Staphylococcus aureus taken with a scanning electron microscope. The width of the image is 25.1 micrometers / ©Paul Gunning, Spot On Micro.

However, as often happens, there are a lot of solutions to this problem in nature. Some microorganisms have long learned to effectively resist their competitors. For example, bacteria of the species Streptomyces formicae produce a specific protein formicamycin, which kills other microbes. For unknown reasons, staphylococcus is not able to develop resistance to it. But to understand the properties of this natural antibiotic and find out why it is so effective, you need to learn how to produce enough protein.

In vivo, Streptomyces formicae secrete formicamycin only under certain circumstances. To stimulate this process, researchers from the John Innes Center (UK) studied the genome of the bacterium. They found both sites responsible for the production of the necessary protein and suppressing it. Through modifications using the CRISPR/Cas9 method, scientists have improved the hereditary material of microorganisms.

The scientists published details about their work in the peer-reviewed journal Cell Chemical Biology (Devine et al., Re-wiring the regulation of the formicamycin biosynthetic gene cluster to enable the development of promising antibacterial compounds).

The modified streptomyces not only has two copies of genes stimulating the production of formicamycin at once, but also lacks "brakes". As a result, the production of a natural antibiotic increased more than the most optimistic forecasts of scientists – ten times. Moreover, disabling the repressor brought an additional advantage of modified bacteria. Now they can produce formicamycin in a liquid medium, which is very convenient for the industrial production of an antibiotic.

Of course, this is not yet a breakthrough on the way to creating a universal cure for MRSA, but a big step. Microbiologists now have the opportunity to obtain formicamycin in large quantities and study it in detail. This will help, if not to develop a new antibiotic based on it, then at least draw conclusions about how staphylococcus becomes vulnerable.

An interesting fact: it was not people who first learned to use streptococci against staphylococci and other bacteria. Ants of the Tetraponera penzigi species live in symbiosis with Streptomyces formicae, which kills pathogenic microbes on the body and in insect dwellings.

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