Study of a combined biological product with antibacterial and probiotic activity
Authors: Neschislyaev V. A. , Shilova E. G. , Nikolaeva A. M. , Orlova E. V. 
Published: October 2023

Scientific relevance. The issue of antimicrobial resistance has acquired global significance, urging the search for and use of alternative antibacterial agents to treat infectious diseases. In particular, this situation prompts wider use of biotechnology-derived medicinal products based    on bacteriophages and probiotics, including those of the metabolite type. The bacteriotropic (antimicrobial and probiotic) properties of pharmaceutical compositions based on bacteriophages and metabolites of probiotic bacteria suggest a qualitatively new combined antibacterial effect, as well as effectiveness against microorganisms resistant to antibiotics.

Aim. The authors aimed to study the properties of a combined biological product with antibacterial and probiotic effects.

Materials  and  methods.  The  study  focused  on  a  combined  biological  product  consisting  of a probiotic agent based on  Lactobacillus  exometabolites  and  a  complex  bacteriophage. The antimicrobial activity evaluation involved the Appelmans method, a disc diffusion method using lawn cultures homologous (Staphylococcus spp., Pseudomonas aeruginosa, Escherichia coli, Proteus spp., Enterococcus spp., Salmonella spp., and Shigella spp.) and non-homologous (Acinetobacter baumannii, Klebsiella pneumoniae, and Yersinia enterocolitica) to the complex bacteriophage, and a bioluminescence inhibition test using  the  genetically  modified  indicator strain E. coli lum+. The study used bacterial strains isolated from various clinical samples and biotopes in bacteriological laboratories of healthcare institutions in the Perm Territory in 2019–2022. The probiotic activity was assessed by the stimulating effect on model microorganisms of the normal flora.

Results. The Appelmans method showed that the combined biological product had high antimicrobial activity against microorganisms homologous to the complex bacteriophage. The titres calculated for the combined biological product and its complex bacteriophage component were comparable and amounted to 10–6.6±0.01 and 10–6.9±0.01, respectively. The disc diffusion method demonstrated that the combined biological product had a more pronounced antibacterial effect on all tested strains than its individual components. The optical density values obtained with the combined biological product were 1.5 and 2 times higher than the values observed with control samples in Bifidobacterium bifidum 1 and Lactobacillus plantarum 8P-А3 cultures, respectively, which demonstrated the stimulating effect of the product on the normal flora.   The study results suggest the compatibility of the phage and probiotic components of the combined biological product, as well as its high antimicrobial activity.

Conclusions. The novel combined biological product has high specific and non-specific antimicrobial activity, which consists in the inhibition of pathogenic bacteria growth without affecting the normal flora. The combined biological product broadens the range of medicinal products having probiotic and antibacterial effects, particularly  on  microorganisms  resistant to antibiotics.