Antimicrobial Activity of Microorganisms Isolated from Ant Nests of Lasius niger.

In this study, the microbial communities of two nests of black garden ants (Lasius niger) in the hollows of stem branches of old apple trees were found to have similar species compositions: each community contained representatives of three species from the Bacillaceae family and one species of actinomycetes from the genus Streptomyces. In total, four types of bacilli and two actinomycetes were isolated. Actinomycetes were identified as Streptomyces antibioticus-like and Streptomyces sp. None of the bacilli had antibiotic activity, whereas both streptomycetes produced antibiotics that inhibited the growth of Gram-positive bacteria in vitro, including isolates from their community. Antibiotic compounds of S. antibioticus-like strain INA 01148 (Institute of New Antibiotics) were identified as actinomycin D and its closest homologue, actinomycin A. Actinomycins presumably change the microbial community of the ant nest substrate as they act against Gram-positive bacteria and against fungi and Gram-negative bacteria. The antibiotic activity of the isolated Streptomyces sp. INA 01156 is of interest, since the substances produced by this strain inhibit the growth of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and vancomycin-resistant strain Leuconostoc mesenteroides VKPM B-4177 (VR) (VKPM-National Collection of Industrial Microorganisms (Russian acronym)).

Synthesis of water-soluble prodrugs of 5-modified 2'-deoxyuridines and their antibacterial activity.

Recently we have synthesized a set of pyrimidine nucleoside derivatives bearing extended alkyltriazolylmethyl substituents at position 5 of the nucleic base, and showed their significant activity against Mycobacterium tuberculosis virulent laboratory strain H37Rv as well as drug-resistant MS-115 strain. The presence of a lengthy hydrophobic substituent leads to the reduction of nucleoside water solubility making their antibacterial activity troublesome to study. A series of water-soluble forms of 5-modified 2'-deoxyuridines 4a-c and 8a-c were synthesized. They appeared at least two orders more soluble compared with the parent compounds 1a and 1b. Their half-hydrolysis time was 5-12 h, which can be considered optimal for prodrugs used in clinics. Obtained compounds showed moderate activity (MIC 48-95 µg·ml-1) against some Gram-positive bacteria including resistant strains of Staphylococcus aureus and Mycobacterium smegmatis and were low cytotoxic for human cell lines (CD50 >> 100 µg·ml-1).

Novel 5-substituted derivatives of 2'-deoxy-6-azauridine with antibacterial activity.

The emergence of new drug-resistant strains of bacteria necessitates the development of principally new antibacterial agents. One of the novel classes of antibacterial agents is nucleoside analogs. We have developed a fast and simple one-pot method for preparation of α- and ß-anomers of 5-modified 6-aza- and 2-thio-6-aza-2'-deoxyuridine derivatives in high yields. 2-Thio derivatives demonstrated moderate activity against Mycobacterium smegmatis (MIC = 0.2-0.8 mM), Staphylococcus aureus (MIC = 0.03-0.9 mM) and some other Gram-positive bacteria. 2'-Deoxy-2-thio-5-phenyl-6-azauridine (2b) effectively suppressed the growth of Gram-negative bacteria Pseudomonas aeruginosa ATCC 27853 (MIC = 0.03 mM)-the one that causes diseases difficult to treat due to high resistance to antibiotics. 5'-Monophosphates of compounds 2a, b and 3a, b were docked into a binding site of Mycobacterium tuberculosis flavin-dependent thymidylate synthase (ThyX) enzyme. The molecular modeling demonstrates the possibility of binding of the 5-modified 2-thio-6-aza-2'-deoxyuridine 5'-monophosphates within the active site of the enzyme and thereby inhibiting the growth of the bacteria.