P105 Treatment of the lower gastrointestinal tract Klebsiella infections by recombinant bacteriocin KvarIa
Karaliute, I.(1);Ramonaite, R.(1);Kupcinskas, J.(2);Misiunas, A.(3);Denkovskiene, E.(3);Gleba, Y.(4);Razanskiene, A.(3);Skieceviciene, J.(1);
(1)Lithuanian University of Health Sciences, Institute for Digestive Research, Kaunas, Lithuania;(2)Lithuanian University of Health Sciences, Department of Gastroenterology, Kaunas, Lithuania;(3)UAB Nomads, Nomad Bioscience Gmbh, Vilnius, Lithuania;(4)NOMAD Bioscience GmbH, NOMAD Bioscience GmbH, Halle, Germany;
Background
Hospital-acquired infections (HAI) are one of the leading worldwide health care issues. The most prevalent HAI are the Klebsiella species. K. quasipneumoniae strains tend to colonize the gastrointestinal tract (GI) and show high rates of resistance against antibiotics. Orally delivered recombinant bacteriocins, like klebicins, could be employed as oral antimicrobials to eradicate multidrug-resistant Klebsiella from the intestinal tract prior to/during hospitalization.
Methods
This study aimed to investigate the antimicrobial efficacy of orally delivered Eudragit - coated klebicin (KvarIa) in a murine lower gastrointestinal tract model of K. quasipneumoniae infection. Four study groups were used (3 animals/group) to test the antimicrobial efficacy of orally delivered klebicin KvarIa: vehicle-only group (control, phosphate-buffered saline), and other three groups with bacteria, antibiotic therapy, and 100 µg of uncoated Kvarla, 100 µg coated KvarIa, 1000 µg coated KvarIa. Faecal and tissue samples were used for Klebsiella haemolysin gene (khe) analysis using RT-PCR.
Results
The gastrointestinal K. quasipneumoniae colonization was achieved only in the antibiotic-treated mice groups ((i) penicillin, streptomycin or (ii) penicillin, streptomycin, and metronidazole) followed by the introduction of K. quasipneumoniae. Analysis of the antimicrobial efficacy of Kvarla showed that coated-KvarIa significantly reduced colonization of K. quasipneumoniae in both mice groups compared to the control group. The amounts of K. quasipneumoniae changed from 6.3 x 107 CFU/50mg on the 18th day to 3.9 x 105 CFU/50mg on the 22nd day (p = 0.01) in the Eudragit S100-coated KvarIa 100 µg group and from 4.0 x 107 CFU/50mg on the 18th day to 1.6 x 105 CFU/50mg on 22nd day (p = 0.009) in the Eudragit S100-coated KvarIa 1000 µg group.
Conclusion
Our study demonstrates that colonization of mice intestinal tract by K. quasipneumoniae can be achieved after eradication of resident gut microbiota with antibiotics. Furthermore, using this murine model, we showed that orally delivered encapsulated klebicins substantially reduce K. quasipneumoniae colonization in the lower gastrointestinal tract.