Introduction
Antimicrobial resistance is a global problem and antibiotic-resistant infections are one of the leading causes of death for people of all ages. Antibiotic-resistant Klebsiella pneumoniae has reached up to 70 percent of global drug resistance rates, with infection-related mortality rates ranging 40-70 percent [1,2]. K. pneumoniae is a causative agent of several types of infections: respiratory, urinary, gastrointestinal tract infections, and many others. Classically, these infections occur in hospitalized or otherwise immunocompromised patients and are routinely treated with β-lactams and other antibiotics effective against Enterobacteriaceae. However, antibiotic-resistant K. pneumoniae has emerged separately across the world [3]. For this reason, there is a rapidly growing demand for new antimicrobial agents, like recombinant bacteriocins, directed against antibiotic-resistant bacteria.
Aims & Methods
The aim of this study was to compare recombinant bacteriocins (klebicin-KvarM) and antibiotic efficacy against K. pneumoniae infection in the gastrointestinal tract. Antimicrobial efficacy of orally delivered klebicin KvarM and antibiotics in treatment of K. pneumoniae infection was tested using four study groups: control group (natural microbiota) (Group 1); K. pneumoniae (ATCC 43816; 107 CFU/50 µl) (Group 2); K. pneumoniae (ATCC 43816; 107 CFU/50 µl) and KvarM coated to be released in the small and large intestines (5 mg/ml) (Group 3); K. pneumoniae (ATCC 43816; 107 CFU/50 µl) and broad-spectrum ciprofloxacin (2 mg/200 µl) (Group 4). From faecal samples, which were collected on different experimental days, we performed real-time polymerase chain reaction (RT-PCR) to detect the amplification of the haemolysin gene (khe), which is a specific marker for Klebsiella genus bacteria.
Results
The gastrointestinal K. pneumoniae infection in mice was achieved orally using pipetting method without antibiotic pre-treatment. After induction of therapy substances once daily for 4 days, there was a significant difference between Group 2 and Group 3 (p = 0,05). In Group 3 the amounts of K. pneumoniae bacteria changed from 1,4 x 106 CFU after K. pneumoniae administration to 1,7 x 102 CFU after the last dose of therapy (63,9 percent efficacy) (p = 0,026). Comparing Group 2 and Group 4 results did not reach statistical significance (p = 0,423). In Group 4 K. pneumoniae count changed from 8,75 x 105 CFU after K. pneumoniaeadministration to 3,51 x 103 CFU after antibiotic therapy, having 37,1 percent of efficacy (p = 0,1002).
Conclusion
Comparing the antibiotic and bacteriocins efficacy, statistically significant results were obtained – the effect of bacteriocin KvarM was more effective in the treatment of Klebsiella pneumoniae colonization of the digestive tract.
References
1. Murray CJ, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet. 2022;12;399(10325):629–55.
2. Alvarez-Uria G, Gandra S, Mandal S, Laxminarayan R. Global forecast of antimicrobial resistance in invasive isolates of Escherichia coli and Klebsiella pneumoniae. International Journal of Infectious Diseases. 2018;1;68:50–3.
3. Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Vol. 8, Frontiers in Cellular and Infection Microbiology. Frontiers Media S.A.; 2018.
Disclosure
There was no conflict of interest
