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Background Klebsiella quasipneumoniae  is an opportunistic pathogen causing antibiotic-resistant infections of the gastrointestinal tract in many clinical cases. Orally delivered bioactive  Klebsiella -specific antimicrobial proteins, klebicins, could be a promising method to eradicate  Klebsiella  species infecting the gut. Methods Mouse infection model was established based on infection of antibiotic-treated BALB/C mice with  K. quasipneumoniae  strain DSM28212. 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. Because of the general sensitivity of bacteriocins to gastroduodenal proteases, Kvarla doses were coated with Eudragit®, a GMP-certified formulation agent that releases the protein at certain pH. The coating treatment was selected based on measurements of mouse GI tract pH. The quantity of  Klebsiella  haemolysin gene ( khe ) in faecal samples of the study animals was used to quantify the presence of  Klebsiella . Results GI colonization of  K. quasipneumoniae  was achieved only in the antibiotic-treated mice groups. Significant changes in  khe  marker quantification were found after the use of Eudragit® S100 formulated klebicin KvarIa, at both doses, with a significant reduction of  K. quasipneumoniae  colonization compared to the vehicle-only control group. Conclusions Mouse GI tract colonization with  K. quasipneumoniae  can be achieved if natural gut microbiota is suppressed by prior antibiotic treatment. The study demonstrates that GI infection caused by  K. quasipneumoniae  can be significantly reduced using Eudragit®-protected klebicin KvarIa.

Reduction of gastrointestinal tract colonization by Klebsiella quasipneumoniae using antimicrobial protein KvarIa