Foods and Raw Materials Foods and Raw Materials Foods and Raw Materials 2308-4057 2310-9599 39541 10.21603/2308-4057-2020-2-377-384 Research Article Research Article Research Article Antibiotic activity and resistance of lactic acid bacteria and other antagonistic bacteriocin-producing microorganisms Antibiotic activity and resistance of lactic acid bacteria and other antagonistic bacteriocin-producing microorganisms Yang Yong Yang Yong https://orcid.org/0000-0002-4921-8997 Babich Olga O. Babich Olga O. https://orcid.org/0000-0001-7910-8388 Sukhikh Stanislav A. Sukhikh Stanislav A. stas-asp@mail.ru https://orcid.org/0000-0002-4622-8241 Zimina Mariya I. Zimina Mariya I. https://orcid.org/0000-0002-3536-562X Milentyeva Irina S. Milentyeva Irina S. Qiqihar University Qiqihar Китайская Республика Qiqihar University Qiqihar Taiwan Immanuel Kant Baltic Federal University Kaliningrad Россия Immanuel Kant Baltic Federal University Kaliningrad Russian Federation Immanuel Kant Baltic Federal University Kaliningrad Россия Immanuel Kant Baltic Federal University Kaliningrad Russian Federation Immanuel Kant Baltic Federal University Kaliningrad Россия Immanuel Kant Baltic Federal University Kaliningrad Russian Federation Kemerovo State University Kemerovo Россия Kemerovo State University Kemerovo Russian Federation 8 2 377 384 http://jfrm.ru/en/issues/1629/1725/

Introduction. Increased resistance of microorganisms to traditional antibiotics has created a practical need for isolating and synthesizing new antibiotics. We aimed to study the antibiotic activity and resistance of bacteriocins produced by lactic acid bacteria and other microorganisms. Study objects and methods. We studied the isolates of the following microorganism strains: Bacillus subtilis, Penicillium glabrum, Penicillium lagena, Pseudomonas koreenis, Penicillium ochrochloron, Leuconostoc lactis, Lactobacillus plantarum, Leuconostoc mesenteroides, Pediococcus acidilactici, Leuconostoc mesenteroides, Pediococcus pentosaceus, Lactobacillus casei, Lactobacillus fermentum, Bacteroides hypermegas, Bacteroides ruminicola, Pediococcus damnosus, Bacteroides paurosaccharolyticus, Halobacillus profundi, Geobacillus stearothermophilus, and Bacillus caldotenax. Pathogenic test strains included Escherichia coli, Salmonella enterica, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus mycoides, Alcaligenes faecalis, and Proteus vulgaris. The titer of microorganisms was determined by optical density measurements at 595 nm. Results and discussion. We found that eleven microorganisms out of twenty showed high antimicrobial activity against all test strains of pathogenic and opportunistic microorganisms. All the Bacteroides strains exhibited little antimicrobial activity against Gramnegative test strains, while Halobacillus profundi had an inhibitory effect on Gram-positive species only. The Penicillium strains also displayed a slight antimicrobial effect on pathogenic test strains. Conclusion. The antibiotic resistance of the studied lactic acid bacteria and other bacteriocin-producing microorganisms allows for their use in the production of pharmaceutical antibiotic drugs.

Introduction. Increased resistance of microorganisms to traditional antibiotics has created a practical need for isolating and synthesizing new antibiotics. We aimed to study the antibiotic activity and resistance of bacteriocins produced by lactic acid bacteria and other microorganisms. Study objects and methods. We studied the isolates of the following microorganism strains: Bacillus subtilis, Penicillium glabrum, Penicillium lagena, Pseudomonas koreenis, Penicillium ochrochloron, Leuconostoc lactis, Lactobacillus plantarum, Leuconostoc mesenteroides, Pediococcus acidilactici, Leuconostoc mesenteroides, Pediococcus pentosaceus, Lactobacillus casei, Lactobacillus fermentum, Bacteroides hypermegas, Bacteroides ruminicola, Pediococcus damnosus, Bacteroides paurosaccharolyticus, Halobacillus profundi, Geobacillus stearothermophilus, and Bacillus caldotenax. Pathogenic test strains included Escherichia coli, Salmonella enterica, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus mycoides, Alcaligenes faecalis, and Proteus vulgaris. The titer of microorganisms was determined by optical density measurements at 595 nm. Results and discussion. We found that eleven microorganisms out of twenty showed high antimicrobial activity against all test strains of pathogenic and opportunistic microorganisms. All the Bacteroides strains exhibited little antimicrobial activity against Gramnegative test strains, while Halobacillus profundi had an inhibitory effect on Gram-positive species only. The Penicillium strains also displayed a slight antimicrobial effect on pathogenic test strains. Conclusion. The antibiotic resistance of the studied lactic acid bacteria and other bacteriocin-producing microorganisms allows for their use in the production of pharmaceutical antibiotic drugs.

 Lactic acid bacteria bacteriocins antibiotic properties antibiotic resistance natural sources isolates Lactic acid bacteria bacteriocins antibiotic properties antibiotic resistance natural sources isolates

INTRODUCTIONNew microorganisms that are resistant to traditionalantibiotics have recently become known to medicine [1].Today, large numbers of people worldwide are dyingfrom various infections caused by antibiotic-resistantstrains of microorganisms [2]. Therefore, there is anincreasingly important scientific and practical need fornew antimicrobial drugs with a wide spectrum of action.Modern researchers are actively studyingbacteriocins produced by Gram-positive bacteria,which are antibiotic proteins [3]. Due to their complexstructure, bacteriocins can be classified as peptideswith different activity, gene control, and biochemicalprocesses [4, 5]. They do not develop antimicrobialresistance and therefore are widely used in medicineand pharmacology [4, 6]. These substances are known  for high antibiotic activity against closely related strainsof microorganisms. Lactic acid microorganisms areamong the most effective producers of bacteriocins andbacteriocin-like agents [3].Bacteriocinogenesis has apparently evolved asa result of adaptation and survival in a harmfulenvironment, having occupied a certain niche inmicrobiology [7]. Bacteriocins are produced by lacticacid bacteria – natural microbiota in the digestivesystem of humans and animals, as well as in foodraw materials, products, or animal feed. Bacteriocinscolonize natural and industrial substrates [8–10].Most often, they do not dominate over saprophyticmicroorganisms of spore and non-spore forms, overcocci, yeasts, molds, and Gram-negative bacteria, whichinhibit antibiotics [11, 12].Bacteriocin production is a complex process thatrequires optimal parameters to affect the system. Notall bacteria can synthesize bacteriocins. It has beenproved that the ability to synthesize a small amountof bacteriocinogenic substances by individual strainsis hereditary [13, 14]. However, the synthesis canbe improved by genetic engineering, DNA-tropicsubstances ultraviolet rays, peroxides, chemicalmutagens, and other agents [15, 16]. Since mid-20thcentury, extensive experiments have been in operation tocreate new bacteriocin-producing bacteria.A number of Gram-positive strains, such asLactobacillus, Streptococcus, Bacillus, Mycobacterium,Staphylococcus, Corynebacterium, Leuconostoc, Sarcina,Micrococcus, Clostridium and Streptomyces, have beenreported to synthesize bacteriocins [2, 3, 17, 18].A lot of current research is focused on bacteriocinsproduced by lactic acid microorganisms. For example,diacetin B-1, a bacteriocin isolated from Lactococcuslactis, consists of 37 amino acid residues and has amolecular weight of 4300 Da [19–21]. Scientists know of14 strains of Lactococcus lactis capable of synthesizingbacteriocins. All bacteriocins inhibit the growth ofS. aureus, P. acidilactici, L. Plantarum, and manyListeria species [14, 22, 23].Amylovorin 471, a bacteriocin produced byLactobacillus amylovorus D CE 4 71, i s u sed a s a b iopreservativein food and feed [24].A purified form of enterocin A obtained fromEnterococcus faecium contains 47 amino acid residues,including 4 cystine residues, and has a molecular weightof 4289 Da. Enterocin A has a similar amino acidsequence to that of nisin, a bacteriocin produced bylactic acid bacteria [25].Bacteriocins are also formed by other types ofenterococci. For example, E. faecalis S-48 produces a80 kDa bacteriocin that is sensitive to proteases and hasan inhibitory effect on E. faecalis [26].Thus, many infectious diseases can be preventedand treated by isolating new strains of lactic acidmicroorganisms that produce bacteriocins withantibacterial action [27, 28]. Unlike Lactobacillusstrains, the antimicrobial activity of Lactococcus strainshas not been well studied [2, 14].Therefore, there is an urgent need for isolating newantimicrobial and antibiotic-resistant bacteriocinsformed by lactic acid bacteria and other antagonistmicroorganisms, as well as studying their properties andprospects for the pharmaceutical industry [29, 30].We aimed to study the antibiotic activity andresistance of bacteriocins produced by lactic acidbacteria and other antagonist microorganisms isolatedfrom natural systems in the Kemerovo region.In particular, we aimed to:– study the antimicrobial effect of lactic acidbacteria and other antagonist bacteriocin-producingmicroorganisms on pathogenic and opportunisticmicroflora that can cause severe infectious diseases inhumans;– select the isolates of microorganisms with bacteriocinproperties (antimicrobial activity) to determine theirantibiotic resistance; and– examine the resistance of lactic acid bacteria and otherantagonist microorganisms to the main antibiotics ofvarious series.STUDY OBJECTS AND METHODSMicrobial communities in various habitats(soil, water, animal gastrointestinal tract, animalproducts, etc.) were used as natural systems fromwhich we isolated strains of bacteriocin-producingmicroorganisms. The sampling took place in theKemerovo region.Our objects of study included the isolates ofbacteriocin-producing microorganism strains, suchas Bacillus subtilis, Penicillium glabrum, Penicilliumlagena, Pseudomonas koreenis, Penicilliumochrochloron, Leuconostoc lactis, Lactobacillusplantarum, Leuconostoc mesenteroides, Pediococcusacidilactici, Leuconostoc mesenteroides, Pediococcuspentosaceus, Lactobacillus casei, Lactobacillusfermentum, Bacteroides hypermegas, Bacteroidesruminicola, Pediococcus damnosus, Bacteroidespaurosaccharolyticus, Halobacillus profundi,Geobacillus stearothermophilus, and Bacilluscaldotenax.Prior to isolation, we incubated microorganismson an agar medium melted and poured into Petridishes (covering a third or a quarter of the area), thensterilized and cooled. The incubation lasted 4–5 daysat 30°C (until complete or almost complete sporulationby vegetative cells). Then, the grown colonies weresuspended in 30 mL of a sterile liquid T3 medium.The flasks with the inoculated medium were placedon an orbital shaker (220 rpm, 72–80 h, 30°C). Thestage of sporulation was determined by phase contrastmicroscopy. At the end of incubation, we found98–100% of spores and crystals in the liquid medium379Yang Y. et al. Foods and Raw Materials, 2020, vol. 8, no. 2, pp. Х–Хin relation to the vegetative cells. The number ofcolony-forming units per ml of culture fluid (CFU/mL)was determined with a series of dilutions followedby incubation in Petri dishes with a T3 medium (fivereplicates) for 24 h at 30°C. After incubation, wecounted the grown colonies and expressed the results inCFU/ml, or spores/ml in our case.We used the following pathogenic test strains:– Escherichia coli ATCC 25922 – opportunistic bacteriacausing gastroenteritis in humans;– Salmonella enterica ATCC 14028 – pathogenicbacteria causing gastroenteritis in humans;– Staphylococcus aureus ATCC 25923 – pathogenicbacteria causing pneumonia, meningitis, osteomyelitis,endocarditis, infectious toxic shock and sepsis inhumans;– Pseudomonas aeruginosa B6643 – opportunisticbacteria causing nosocomial infections in humans;– Bacillus mycoides EMTC (Russian collection ofextremophilic microorganisms and type cultures)9 – opportunistic bacteria causing foodborne toxicinfections in humans;– Alcaligenes faecalis EMTC 1882 – opportunisticbacteria causing septicemia and meningitis in newbornsand intra-abdominal infections in adults;– Proteus vulgaris ATCC 63 – opportunistic bacteriacausing acute intestinal infections in humans.Cultivation of microorganism test strains.Escherichia coli ATCC 25922 was cultivated on amedium composed of 10 g tryptone, 5 g yeast extract,10 g sodium chloride, and 1 L water (pH 7.5–8.0, 37°C).Salmonella enterica ATCC 14028 was cultivated on amedium composed of 10 g peptic digest of animal tissue,5 g meat extract, 5 g glucose, 4 g sodium hydrogenphosphate, 0.3 g iron sulfate, 8 g bismuth sulfite,0.025 g brilliant green, 20 g agar-agar, and 1 L water(pH 7.5–7.9, 35°С).Staphylococcus aureus ATCC 25923 was cultivatedon a medium composed of 10 g casein hydrolysate,2.5 g yeast extract, 30 g gelatin, 10 g D-mannitol, 55 gsodium chloride, 75 g ammonium sulfate, 5 g potassiumhydrogen phosphate, 15 g agar-agar, and 1 L water(рН 6.8–7.2, 30°С).Pseudomonas aeruginosa B6643 was cultivated on amedium composed of 1 L meat water, 5 g NaCl, and 10 gpeptone (рН 6.8–7.0, 37°С).Bacillus mycoides EMTC 9 was cultivated on amedium composed of 10 g casein hydrolysate, 2.5 gyeast extract, 5 g glucose, 2.5 g potassium hydrogenphosphate, 3 g agar-agar, and 1 L water (рН 7.2–7.6,30°С).Alcaligenes faecalis EMTC 1882 was cultivated on amedium composed of 10 g special peptone, 5 g sodiumchloride, 0.3 g sodium azide, 0.06 g chromogenicmixture, 2 g Tween-80, 1.25 g sodium hydrogenphosphate, 15 g agar-agar, and 1 L water (рН 7.3–7.5,37°С).Proteus vulgaris ATCC 63 was cultivated on amedium composed of 8 g peptone, 5 g sodium chloride,1 g sodium deoxycholate, 1.5 g chromogenic mixture,10.5 g propylene glycol, 15 g agar-agar, and 1 L water(рН 7.1–7.5, 37°С).The quantity of microorganisms (titer) in thesuspensions of overnight broth cultures grown onstandard media was determined by optical densitymeasurements at 595 nm.Lactic acid bacteria and other antagonistmicroorganisms isolated from natural sources in theKemerovo region were assessed for their antimicrobialaction in two ways, using the diffusion method andmeasuring optical density.Diffusion method. Test strain bacteria inoculatedonto an agar medium using the spread plate techniquewere immediately covered with paper disks impregnatedwith the metabolites of microorganisms under study(10 μL/disk). A disc with a nutrient medium was usedas a control, and a disc with ciprofloxacin (a standardantibiotic) was used as a reference drug. The plates wereincubated for 24 h at a temperature optimal for each teststrain. The quantity of microorganisms was determinedby measuring the size (mm) of a transparent zone aroundthe disc, indicating the absence of microbial growth [31].Optical density measurement. Test strain bacteriawere incubated with the metabolites in 96-well cultureplates [32]. We resuspended broth cultures aged for12 h in a medium corresponding to the species ofmicroorganisms to inoculate, bringing their amountto ~ 105 CFU/mL. At the same time, we added thecell suspension and the metabolites under study to thewells in an amount of 1/10 of the total volume. A liquidnutrient medium was used as a control and ciprofloxacinwas used as a reference drug (10 μg/mL). The totalvolume of the suspension in the well was 200 μL. Theexperiments were performed in duplicate. Incubationwas carried out on a shaker at 580 rpm at a temperatureoptimal for each test strain. After 24 h, we measuredthe optical density on a PICO01 spectrophotometer(Picodrop Limited, UK) at 595 nm. The bactericidalactivity was determined by changes in the opticaldensity compared to the control. In the wells where cellgrowth stopped or slowed down, the optical density waslower than in those with normal growth.Microbial spores were stained according to theSchaeffer-Fulton method. The method uses a combinedeffect of a concentrated brilliant green solution andtemperature on the impermeable spore membrane withfurther decolorization of the cytoplasm of a vegetativecell and its contrast staining with safranin. Microscopicexamination showed that the spores were stained greenand the cells, red. To establish the presence of flagella,we studied the mobility of cultures in the “squashedstraw” preparations [33].The antibiotic resistance was determined by thezones of growth inhibition for the isolates with antibioticdiscs. For this, we inoculated isolate cells onto atemporary medium using the spread plate technique,380Yang Y. et al. Foods and Raw Materials, 2020, vol. 8, no. 2, pp. Х–Хwith antibiotic discs on the agar. The experimentalresults were recorded after 24 hours of cultivation in theincubator at 28°C [31].RESULTS AND DISCUSSIONTable 1 shows the results of using the diffusionmethod to assess the antimicrobial properties of lacticacid bacteria and other microorganisms isolated fromnatural sources in the Kemerovo region.Of the twenty microorganism strains under study,eleven exhibited high antimicrobial activity againstall test strains of pathogenic and opportunisticmicroorganisms (Bacillus subtilis, Leuconostoclactis, Lactobacillus plantarum, LeuconostocTable 2 Antibiotic resistance of Bacillus subtilis isolateAntibiotic Diameter of a growth inhibition zone, mmContent of bacteria in 1 ml of strain culture1×107 5×107 1×108 5×108 1×109 5×109Ampicillin 0 0 0 0 0 0Benzylpenicillin 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5Carbenicillin 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0Polymyxin 0 0 0 0 0 0Streptomycin 13.5 ± 2.5 13.5 ± 2.5 13.5 ± 2.5 13.5 ± 2.5 13.5 ± 2.5 13.5 ± 2.5Gentamicin 0 0 0 0 0 0Clotrimazole 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0Levomycitin 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0 19.0 ± 1.0Tetracycline 0 0 0 0 0 0Monomycin 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5 1.5 ± 0.5Neomycin 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5Ceporin 17.5 ± 1.5 17.5 ± 1.5 17.5 ± 1.5 17.5 ± 1.5 17.5 ± 1.5 17.5 ± 1.5Kanamycin 18.5 ± 2.5 18.5 ± 2.5 18.5 ± 2.5 18.5 ± 2.5 18.5 ± 2.5 18.5 ± 2.5Novogramon 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5Table 1 Antimicrobial activity of natural microorganism isolates by the diffusion method (solid nutrient medium)Microorganism isolates Lysis zone diameter, mmEscherichiacoli ATCC25922–SalmonellaentericaATCC14028–StaphylococcusaureusATCC25923+PseudomonasaeruginosaB6643–BacillusmycoidesEMTC 9+AlcaligenesfaecalisEMTC1882–ProteusvulgarisATCC 63–Control 0 0 0 0 0 0 0Ciprofloxacin (C) 21.0 ± 1.1 24.0 ± 1.2 19.0 ± 1.0 22.0 ± 1.1 25.0 ± 1.3 23.0 ± 1.2 20.0 ± 1.0Bacillus subtilis 18.0 ± 0.9 20.0 ± 1.0 17.0 ± 0.9 20.0 ± 1.0 22.0 ± 1.1 20.0 ± 1.0 17.0 ± 0.9Penicillium glabrum 0 0 5.0 ± 0.3 0 0 0 7.0 ± 0.4Penicillium lagena 6.0 ± 0.3 10.0 ± 0.5 0 0 0 0 0Pseudomonas koreenis 12.0 ± 0.6 5.0 ± 0.3 18.0 ± 0.9 0 0 17.0 ± 0.9 15.0 ± 0.8Penicillium ochrochloron 0 0 0 0 0 6.0 ± 0.3 0Leuconostoc lactis 20.0 ± 1.0 22.0 ± 1.1 17.0 ± 0.9 21.0 ± 1.1 24.0 ± 1.2 21.0 ± 1.1 18.0 ± 0.9Lactobacillus plantarum 19.0 ± 1.0 18.0 ± 0.9 15.0 ± 0.8 19.0 ± 1.0 22.0 ± 1.1 21.0 ± 1.1 17.0 ± 0.9Leuconostoc mesenteroides 17.0 ± 0.9 20.0 ± 1.0 16.0 ± 0.8 19.0 ± 1.0 22.0 ± 1.1 20.0 ± 1.0 18.0 ± 0.9Pediococcus acidilactici 20.0 ± 1.0 21.0 ± 1.1 17.0 ± 0.9 19.0 ± 1.0 23.0 ± 1.2 21.0 ± 1.1 18.0 ± 0.9Leuconostoc mesenteroides 15.0 ± 0.8 18.0 ± 0.9 14.0 ± 0.7 17.0 ± 0.9 20.0 ± 1.0 17.0 ± 0.9 15.0 ± 0.8Pediococcus pentosaceus 21.0 ± 1.1 20.0 ± 1.0 17.0 ± 0.9 19.0 ± 1.0 24.0 ± 1.2 22.0 ± 1.1 18.0 ± 0.9Lactobacillus casei 18.0 ± 0.9 19.0 ± 1.0 15.0 ± 0.8 10.0 ± 0.5 20.0 ± 1.0 17.0 ± 0.9 15.0 ± 0.8Lactobacillus fermentum 15.0 ± 0.8 18.0 ± 0.9 14.0 ± 0.7 19.0 ± 1.0 21.0 ± 1.1 17.0 ± 0.9 15.0 ± 0.8Bacteroides hypermegas 12.0 ± 0.6 10.0 ± 0.5 0 14.0 ± 0.7 0 9.0 ± 0.5 11.0 ± 0.6Bacteroides ruminicola 7.0 ± 0.4 11.0 ± 0.6 0 12.0 ± 0.6 0 7.0 ± 0.4 10.0 ± 0.5Pediococcus damnosus 17.0 ± 0.9 22.0 ± 1.1 16.0 ± 0.8 20.0 ± 1.0 23.0 ± 1.2 19.0 ± 1.0 18.0 ± 0.9Bacteroides paurosaccharolyticus 15.0 ± 0.8 13.0 ± 0.7 0 16.0 ± 0.8 0 12.0 ± 0.6 14.0 ± 0.7Halobacillus profundi 0 0 11.0 ± 0.6 0 14.0 ± 0.7 0 0Geobacillus stearothermophilus 20.0 ± 1.0 22.0 ± 1.1 18.0 ± 0.9 19.0 ± 1.0 22.0 ± 1.1 20.0 ± 1.0 18.0 ± 0.9Bacillus caldotenax 18.0 ± 0.9 23.0 ± 1.2 17.0 ± 0.9 20.0 ± 1.0 21.0 ± 1.1 22.0 ± 1.1 19.0 ± 1.0381Yang Y. et al. Foods and Raw Materials, 2020, vol. 8, no. 2, pp. Х–Хmesenteroides, Pediococcus acidilactici, Pediococcuspentosaceus, Lactobacillus casei, Lactobacillusfermentum, Pediococcus damnosus, Geobacillusstearothermophilus, Bacillus caldotenax).Bacteroides hypermegas, Bacteroides ruminicola,and Bacteroides paurosaccharolyticus showedinsignificant antimicrobial activity against Gramnegativetest strains, while Halobacillus profundi hadan inhibitory effect on Gram-positive species only.Penicillium glabrum had a slight antimicrobial effect onStaphylococcus aureus, Proteus vulgaris, and Shigellaflexneri; Penicillium lagena, on the test strains ofEscherichia coli, Salmonella enterica, Shigella flexneri,Aspergillus flavus, and Penicillium citrinum; Penicilliumochrochloron, on the test strains of Alcaligenes faecalisand Listeria monocytogenes.For further studies of antibiotic resistance, weselected four isolates with maximum antimicrobialactivity against pathogenic and opportunistic teststrains, namely Bacillus subtilis, Leuconostoclactis, Lactobacillus plantarum, and Leuconostocmesenteroides.These isolates were tested for antibiotic resistance,i.e. resistance of a strain to one or more antibacterialdrugs, or decreased sensitivity (immunity) of a cultureto the action of an antibacterial substance.Antibiotic resistance can develop as a result ofnatural selection through random mutations and/or antibiotic exposure. Microorganisms are able totransmit genetic information about antibiotic resistancethrough horizontal gene transfer. In addition, antibioticresistance can be induced artificially by genetictransformation, for example, by introducing artificialgenes into the genome of a microorganism [13].Tables 2–5 show the results of studying the antibioticresistance of microorganisms isolated from naturalsources in the Kemerovo region.Table 3 Antibiotic resistance of Leuconostoc lactis isolateAntibiotic Diameter of a growth inhibition zone, mmContent of bacteria in 1 ml of strain culture1×107 5×107 1×108 5×108 1×109 5×109Ampicillin 29.0 ± 1.0 29.0 ± 1.0 29.0 ± 1.0 29.0 ± 1.0 29.0 ± 1.0 29.0 ± 1.0Benzylpenicillin 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5Carbenicillin 19.0 ± 2.0 19.0 ± 2.0 19.0 ± 2.0 19.0 ± 2.0 19.0 ± 2.0 19.0 ± 2.0Polymyxin 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5Streptomycin 0 0 0 0 0 0Gentamicin 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5 22.5 ± 2.5Clotrimazole 4.0 ± 1.0 4.0 ± 1.0 4.0 ± 1.0 4.0 ± 1.0 4.0 ± 1.0 4.0 ± 1.0Levomycitin 18.0 ± 2.0 18.0 ± 2.0 18.0 ± 2.0 18.0 ± 2.0 18.0 ± 2.0 18.0 ± 2.0Tetracycline 0 0 0 0 0 0Monomycin 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0 6.0 ± 1.0Neomycin 11.0 ± 1.0 11.0 ± 1.0 11.0 ± 1.0 11.0 ± 1.0 11.0 ± 1.0 11.0 ± 1.0Ceporin 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0Kanamycin 0 0 0 0 0 0Novogramon 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5Table 4 Antibiotic resistance of Lactobacillus plantarum isolateAntibiotic Diameter of a growth inhibition zone, mmContent of bacteria in 1 ml of strain culture1×107 5×107 1×108 5×108 1×109 5×109Ampicillin 25.0 ± 2.0 25.0 ± 2.0 25.0 ± 2.0 25.0 ± 2.0 25.0 ± 2.0 25.0 ± 2.0Benzylpenicillin 28.5 ± 1.5 28.5 ± 1.5 28.5 ± 1.5 28.5 ± 1.5 28.5 ± 1.5 28.5 ± 1.5Carbenicillin 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0 20.0 ± 2.0Polymyxin 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5 21.5 ± 1.5Streptomycin 0 0 0 0 0 0Gentamicin 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5 16.5 ± 1.5Clotrimazole 0 0 0 0 0 0Levomycitin 27.0 ± 1.0 27.0 ± 1.0 27.0 ± 1.0 27.0 ± 1.0 27.0 ± 1.0 27.0 ± 1.0Tetracycline 30.0 ± 2.0 30.0 ± 2.0 30.0 ± 2.0 30.0 ± 2.0 30.0 ± 2.0 30.0 ± 2.0Monomycin 15.0 ± 2.0 15.0 ± 2.0 15.0 ± 2.0 15.0 ± 2.0 15.0 ± 2.0 15.0 ± 2.0Neomycin 10.0 ± 2.0 10.0 ± 2.0 10.0 ± 2.0 10.0 ± 2.0 10.0 ± 2.0 10.0 ± 2.0Ceporin 0 0 0 0 0 0Kanamycin 0 0 0 0 0 0Novogramon 10.0 ± 1.0 10.0 ± 1.0 10.0 ± 1.0 10.0 ± 1.0 10.0 ± 1.0 10.0 ± 1.0382Yang Y. et al. Foods and Raw Materials, 2020, vol. 8, no. 2, pp. Х–ХAs we can see, Bacillus subtilis proved to beresistant to ampicillin, gentamicin, and tetracycline. Itexhibited high sensitivity to neomycin, novogramon,kanamycin, carbenicillin, levomycitin, and ceporin,but low sensitivity to benzylpenicillin, monomycin andclotrimazole.Leuconostoc lactis was highly sensitive toampicillin, gentamicin, benzylpenicillin, andnovogramon, insensitive to clotrimazole andmonomycin, and resistant to streptomycin, tetracyclineand kanamycin.Lactobacillus plantarum showed resistance tostreptomycin, clotrimazole, ceporin and kanamycin,high sensitivity to tetracycline, benzylpenicillin, andlevomycitin, and low sensitivity to neomycin andnovogramon.Leuconostoc mesenteroides was resistant tostreptomycin, tetracycline, and kanamycin, insensitiveto clotrimazole and monomycin, and highly sensitiveto ampicillin, ceporin, benzylpenicillin, gentamicin,levomycitin, and novogramon.We found that the isolates with differentconcentrations of microorganisms displayed the sameantibiotic resistance. The diameter of the growthinhibition zone was the same for all concentrations ofmicroorganisms.CONCLUSIONThus, we studied the antibiotic activity andresistance of lactic acid bacteria and other antagonistmicroorganisms isolated from natural sources in theKemerovo region. We established a correlation betweenthe type of isolate and the type of antibiotic. Accordingto the study, eleven microorganisms out of twentyexhibited high antimicrobial activity, while the rest ofthe strains had an insignificant effect on the test strainsand opportunistic microorganisms.We found that all the isolates showed some degreeof resistance to the following antibiotics used to treatinfectious diseases: ampicillin, benzylpenicillin,carbenicillin, polymyxin, streptomycin, gentamicin,clotrimazole, levomycitin, tetracycline, monomycin,neomycin, ceporin, kanamycin, and novogramon.The progressive resistance of the studied bacteriocinproducingmicroorganisms to antibiotics allows for theiruse in the production of pharmaceutical antibiotic drugs.CONTRIBUTIONThe authors were equally involved in the writingof the manuscript and are equally responsible forplagiarism.CONFLICT OF INTERESTThe authors state that there is no conflict of interest.

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