Streptomyces phaeochromogenes BV-204, K-1115A Anthraquinone-Producing Strain: A New Protein Biosynthesis Inhibitor.

In the search for new antibiotics, it is a common occurrence that already known molecules are "rediscovered" while new promising ones remain unnoticed. A possible solution to this problem may be the so-called "target-oriented" search, using special reporter microorganisms that combine increased antibiotic sensitivity with the ability to identify a molecule's damaging effect. The use of such test organisms makes it possible to discover new promising properties even in known metabolites. In this study, we used a high-throughput screening method based on the pDualrep2 dual reporter system, which combines high sensitivity through the use of modified strains of test organisms and makes it possible to easily and accurately identify the interaction mechanisms of a substance and a bacterial cell at the initial stages of screening. This reporter system is unknown in Russia and is significantly superior to its global analogues. In the system, translation inhibition induces the expression of the fluorescent protein Katushka2s, while DNA damage is induced by TurboRFP. Using pDualrep2, we have isolated and described BV-204, an S. phaeochromogenes strain producing K-1115A, the biologically active substance that we have previously described. In our study, K-1115A for the first time has demonstrated antibiotic activity and an ability to inhibit bacterial translation, which was confirmed in vitro in a cell-free translation system for FLuc mRNA. K-1115A's antibacterial activity was tested and confirmed for S. aureus (MRSA) and B. subtilis, its cytotoxicity measured against that for the HEK293 cell line. Its therapeutic index amounted to 2 and 8, respectively. The obtained results open up prospects for further study of K-1115A; so, this can be regarded as the basis for the production of semi-synthetic derivatives with improved therapeutic properties to be manufactured in dosage forms.

Antibiotics from Extremophilic Micromycetes.

Extremophilic microorganisms, which are capable of functioning normally at extremely high or low temperatures, pressure, and in other environmental conditions, have been in the focus of microbiologists' attention for several decades due to the biotechnological potential of enzymes inherent in extremophiles. These enzymes (also called extremozymes) are used in the production of food and detergents and other industries. At the same time, the inhabitants of extreme econiches remained almost unexplored for a long time in terms of the chemistry of natural compounds. In recent years, the emergence of new antibiotic-resistant strains of pathogens, which affect humans and animals has become a global problem. The problem is compounded by a strong slowdown in the development of new antibiotics. In search of new active substances and scaffolds for medical chemistry, researchers turn to unexplored natural sources. In recent years, there has been a sharp increase in the number of studies on secondary metabolites produced by extremophiles. From the discovery of penicillin to the present day, micromycetes, along with actinobacteria, are one of the most productive sources of antibiotic compounds for medicine and agriculture. Many authors consider extremophilic micromycetes as a promising source of small molecules with an unusual mechanism of action or significant structural novelty. This review summarizes the latest (for 2018-2019) experimental data on antibiotic compounds, which are produced by extremophilic micromycetes with various types of adaptation. Active metabolites are classified by the type of structure and biosynthetic origin. The data on the biological activity of the isolated metabolites are summarized.

Antibiotic Activity of Probiotic Strain Bacillus subtilis 534 Against Clinical Isolates of Acinetobacter baumannii.

Probiotic strain Bacillus subtilis 534 is the base of sporobacterin, a pharmaceutical. In submerged culture it showed antibiotic activity against many of gram-positive and gram-negative bacteria and fungi. The spectrum of the antimicrobial activity of the culture fluid depended on the.cultivation time and aeration intensity. It was shown that component No. 1 of the antibiotic complex was effective against clinical isolates of Acinetobacter baumannii: 20 out of 24 isolates were susceptible to component No. 1, including 15 strains out of 16 panresistant isolates.