Probiotic Lactobacillus casei expressing human lactoferrin elevates antibacterial activity in the gastrointestinal tract.
In this study, Lactobacillus casei was used to deliver and express human lactoferrin (hLF) to protect the host against bacterial infection. Full-length hLF cDNA was cloned into a Lactobacillus-specific plasmid to produce the L. casei transformants (rhLF/L. casei). Antimicrobial activity of recombinant hLF was examined in inhibition of bacteria growth in vitro. A mouse model was established to test in vivo antibacterial activity and protective effect of orally-administered probiotic L. casei transformant in the gastrointestinal tract. Trials were conducted in which animals were challenged with E. coli ATCC25922. E. coli colony numbers in duodenal fluid from the group fed with rhLF/L. casei were significantly lower than those of the group fed with wild-type L. casei or placebo (P < 0.01). Histopathological analyses of the small intestine, showed both decreased intestinal injury and increased villi length were observed in the mice fed with rhLF/L. casei as compared with the control groups (P < 0.01). Our results demonstrate that L. casei expressing hLF exhibited antibacterial activity both in in vitro and in vivo. It also provides a potentially large-scale production of hLF as applications for treatment of infections caused by clinically relevant pathogens.
Department of Molecular Biotechnology, Da-Yeh University, Changhwa 515, Taiwan.
Hsiao-Ling
HL
Chen
Yi-Wen
YW
Lai
Chua-Shun
CS
Chen
Te-Wei
TW
Chu
Willie
W
Lin
Chih-Ching
CC
Yen
Ming-Fong
MF
Lin
Ming-Yu
MY
Tu
Chuan-Mu
CM
Chen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D004926:Escherichia coli / Q000254:growth & development; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D007780:Lacticaseibacillus casei / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D007781:Lactoferrin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D019936:Probiotics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D007781:Lactoferrin