Bifidobacteria are some of the major agents that shaped the immune system of many members of the animal kingdom during their evolution. Over recent years, the question of concrete mechanisms underlying the immunomodulatory properties of bifidobacteria has been addressed in both animal and human studies. A possible candidate for this role has been discovered recently. The PFNA cluster, consisting of five core genes, pkb2, fn3, aaa-atp, duf58, tgm, has been found in all gut-dwelling autochthonous bifidobacterial species of humans. The sensory region of the species-specific serine-threonine protein kinase (PKB2), the transmembrane region of the microbial transglutaminase (TGM), and the type-III fibronectin domain-containing protein (FN3) encoded by the I gene imply that the PFNA cluster might be implicated in the interaction between bacteria and the host immune system. Moreover, the FN3 protein encoded by one of the genes making up the PFNA cluster, contains domains and motifs of cytokine receptors capable of selectively binding TNF-α. The PFNA cluster could play an important role for sensing signals of the immune system. Among the practical implications of this finding is the creation of anti-inflammatory drugs aimed at alleviating cytokine storms, one of the dire consequences resulting from SARS-CoV-2 infection.

Investigation of aminoglycoside acetyltransferases in actinobacteria of the genus Streptomyces is an integral part of the study of soil bacteria as the main reservoir and possible source of drug resistance genes. Previously, we have identified and biochemically characterized three aminoglycoside phosphotransferases, which cause resistance to kanamycin, neomycin, paromomycin, streptomycin, and hygromycin B in the strain Streptomyces rimosus ATCC 10970 (producing oxytetracycline), which is resistant to most natural aminoglycoside antibiotics. In the presented work, it was shown that the resistance of this strain to other AGs is associated with the presence of the enzyme aminoglycoside acetyltransferase, belonging to the AAC(2′) subfamily. Induction of the expression of the gene, designated by us as aac(2′)-If, in Escherichia coli cells determines resistance to a wide range of natural aminoglycoside antibiotics (neomycin, gentamicin, tobramycin, sisomycin, and paromomycin) and increases minimum inhibitory concentrations of these antibiotics.

The human gut microbiome is a complex ecosystem that plays a key role in maintaining overall homeostasis and is a dynamic reservoir of antibiotic resistance genes that can be transferred between bacteria in mixed populations. One of the main enzymes that carry out the acetylation of a wide range of substrates is aminoglycoside-N-acetyltransferase (AAC). Previously, the bifunctional enzyme AAC(6')-Ie/APH(2'')-Ia was identified and characterized in Enterococcus and Staphylococcus, which is a clinically important enzyme. Within the framework of this study, genes encoding AAC(3) were identified in the sequenced genomes of strains belonging to Bacteroides and Lactobacillus. In the genomes of strains belonging to most species of Bacteroides, Enterococcus, and Lactobacillus, genes encoding Eis have been identified. The sequences of all identified AAC(3) and Eis do not resemble the sequences of known enzymes. AAC(3) and Eis in these bacteria may have different functions in the human body, including participation in the acetylation of peptides, proteins, and other substrates.

The lack of success in combating the spread of multidrug resistance in pathogenic bacteria forces the scientific community to analyze at a new level of knowledge of the mechanisms, routes of spread, and natural reservoirs containing bacteria that carry antibiotic resistance genes. The classical mechanism of resistance to aminoglycoside antibiotics (AG) is the modification of AG by enzymes, the most common and clinically significant of which are aminoglycoside acetyltransferases (AAC). In this study, genes encoding enzymes belonging to the AAC(2'), AAC(3), AAC(6'), and Eis subfamilies were identified in the sequenced genomes of Streptomyces strains producing AG. Comparative analysis of amino acid sequences showed that the closest homologs for the identified AAC are acetyltransferases from other species of actinobacteria of the genus Streptomyces that do not produce AG (producers of other classes of antibiotics or not producing antibiotics). Comparative phylogenetic analysis of amino acid sequences showed that the enzymes AAC(2′) and Eis are homologs of the acetyltransferases AAC(2′)-I and Eis, previously identified in mycobacteria. The possible role of Eis acetyltransferases in the acetylation of various substrates upon entry into the human body through vesicles containing them is discussed.