Using free microorganisms for industrial processes has some limitations, such as the extensive consumption of substrates for growth, significant sensitivity to the microenvironment, and the necessity of separation from the product and, therefore, the cyclic process. It is widely acknowledged that confining or immobilizing cells in a matrix or support structure enhances enzyme stability, facilitates recycling, enhances rheological resilience, lowers bioprocess costs, and serves as a fundamental prerequisite for large-scale applications. This report summarizes the various cell immobilization methods, including several synthetic (polyvinylalcohol, polyethylenimine, polyacrylates, and Eudragit) and natural (gelatin, chitosan, alginate, cellulose, agar–agar, carboxymethylcellulose, and other polysaccharides) polymeric materials in the form of thin films, hydrogels, and cryogels. Advancements in the production of well-known antibiotics like penicillin and cephalosporin by various strains were discussed. Additionally, we highlighted cutting-edge research related to strain producers of peptide-based antibiotics (polymyxin B, Subtilin, Tyrothricin, varigomycin, gramicidin S, friulimicin, and bacteriocin), glusoseamines, and polyene derivatives. Crosslinking agents, especially covalent linkers, significantly affect the activity and stability of biocatalysts (penicillin G acylase, penicillinase, deacetoxycephalosporinase, L-asparaginase, β-glucosidase, Xylanase, and urease). The molecular weight of polymers is an important parameter influencing oxygen and nutrient diffusion, the kinetics of hydrogel formation, rigidity, rheology, elastic moduli, and other mechanical properties crucial for long-term utilization. A comparison of stability and enzymatic activity between immobilized enzymes and their free native counterparts was explored. The discussion was not limited to recent advancements in the biopharmaceutical field, such as microorganism or enzyme immobilization, but also extended to methods used in sensor and biosensor applications. In this study, we present data on the advantages of cell and enzyme immobilization over microorganism (bacteria and fungi) suspension states to produce various bioproducts and metabolites—such as antibiotics, enzymes, and precursors—and determine the efficiency of immobilization processes and the optimal conditions and process parameters to maximize the yield of the target products.

Hospital-acquired infections are a generally recognized problem for healthcare professionals. Clinical variants of Gram-negative and Gram-positive pathogens are characterized with enhanced antibiotic resistance and virulence due to mutations and the horizontal acquisition of respective genetic determinants. In this study, two Escherichia coli, two Klebsiella pneumoniae, three Pseudomonas aeruginosa, two Staphylococcus aureus, one Staphylococcus epidermidis and one Streptococcus pneumoniae showing broad spectra of antibiotic resistance were isolated from patients suffering from nosocomial infections in a local hospital in Almaty, Kazakhstan. The aim of the study was to compare general and species-specific pathways of the development of virulence and antibiotic resistance through opportunistic pathogens causing hospital-acquired infections. The whole-genome PacBio sequencing of the isolates allowed for the genotyping and identification of antibiotic resistance and virulence genetic determinants located in the chromosomes, plasmids and genomic islands. It was concluded that long-read sequencing is a useful tool for monitoring the epidemiological situation in hospitals. Marker antibiotic resistance mutations common for different microorganisms were identified, which were acquired due to antibiotic-selective pressure in the same clinical environment. The genotyping and identification of strain-specific DNA methylation motifs were found to be promising in estimating the risks associated with hospital infection outbreaks and monitoring the distribution and evolution of nosocomial pathogens.

The new iodine complex (FS-1), including molecular iodine, which is coordinated by lithium, magnesium halides, and bioorganic ligands, possesses high bactericidal activity against various microorganisms, including Mycobacterium sp., Staphylococcus aureus MRSA and MSSA, Escherichia coli, Pseudomonas aeruginosa, etc. FS-1 has synergistic properties with a broad class of antibiotics. The experimental model of tuberculosis in guinea pigs caused by clinical multidrug-resistant strains of Mycobacterium tuberculosis shows antituberculosis, immunomodulatory, and anti-inflammatory activity. FS-1 is characterized by low acute toxicity and lack of genotoxicity and mutagenicity. FS-1 is well distributed to organs and tissues; its pharmacokinetics is linear. The maximum nontoxic dose is 100 mg/kg for rats after 28-day oral administration and 30 mg/kg for rabbits after 180-day oral administration.

Results of inhibitory action of FS-1 drug on antioxidant system of pathogenic mycobacteria tuberculosis, including resistant MDR strain, are presented. The study of the effect of FS-1 drug on the activity of the antioxidant system was carried out on the reference strain Mycobacterium tuberculosis H37Rv and MDR (rifampicin, isoniazid, streptomycin, ethambutol,.thionamide, kanamycin, cycloserine and pyrazinamide resistant) strain Mycobacterium tuberculosis 320. FS-1 drug under experimental conditions in vitro showed a new mechanism of action on mycobacteria tuberculosis - suppression of functional activity of the enzyme superoxide dismutase, which protects the microorganism from oxidative stress. The loss of resistance to oxidative stress by a bacterial cell, i.e. the ability to neutralize highly toxic oxygen radicals, leads to the destruction of cellular structures, metabolic and energy processes, disruption of the respiratory system and, as a result, its death. Antioxidant activity of Mycobacterium tuberculosis H37Rv after exposure with FS-1 preparation at concentrations of 4 mu g/ml is inhibited by 90.64 %, while at concentration of 2 mu g/ml on bacterial culture of this strain - by 89.07 %. The obtained results show significant suppression of functional activity of superoxide dismutase enzyme in bacterial culture of Mycobacterium tuberculosis H37Rv under the influence of FS-1 in these concentrations, showing pronounced inhibitory effect. Similar studies of the effect of iodine-containing FS-1 drug on the antioxidant system were carried out on the bacterial culture of M. tuberculosis multidrug resistant strain 320. It was found that antioxidant activity of FS-1 preparation in concentration 4 mu g/ml is inhibited by 99 %, while in concentrations 2 mu g/ml FS-1preparation suppresses antioxidant activity of strain 320 by 98 %. Thus, the studies showed that the FS-1 preparation at the test concentrations of 4 mu g/ml and 2 mu g/ml has a mechanism for pronounced inhibition of the functional activity of the enzyme superoxide dismutase in Mycobacterium tuberculosis of both the reference sensitive strain H37Rv and the multidrug resistant strain 320. This leads to disruption of the redox transformations of various chemical compounds that form the respiratory process in the bacterial culture, providing the energy demand of the microorganism.

Context: One approach to assessing pharmacodynamic drug interactions is the practical application of the Chou-Talalay theory and its combination index theorem. The algorithm for studying and analysing the effects of combinations, according to Chou-Talalay, allows for the calculation of the direction and strength of pharmacodynamic interactions using the combination index (CI) values and to establish the dose reduction index (DRI) for each component of the combination. The algorithm allows for the analysis of combinations of different qualitative and quantitative compositions and calculates the result of interaction at any level of toxicological effect in laboratories engaged in drug development and research. Aims: To evaluate the effect of FS-1 on the toxicity of rimantadine, oseltamivir, and acetylsalicylic acid (ASA) in combined in vitro experiments. Methods: The combined cytotoxicity effect of drugs was evaluated using neutral red on MDCK cells. The type of drug interaction was determined using the principle of median-effect and CI by correlation of doses and effects, the ratio of the value of programmed cell death to the value of actual cell death using the Chou-Talalay method. Results: It was found that the combination FS-1/rimantadine, FS-1/oseltamivir, and FS-1/ASA can significantly reduce their toxic properties. The CI of the combined use of FS-1/rimantadine was CI = 2.018; FS-1/oseltamivir CI = 13.726, and FS-1/ASA CI = 1.518. Conclusions: The use of Chou-Talalay algorithm makes it possible to develop recommendations for the rational use and dosing of drug combinations in clinical practice, as well as to assess the prospects for the development of new combined therapeutic technologies.