Surface display of uropathogenic Escherichia coli FimH in Lactococcus lactis: In vitro characterization of recombinant bacteria and its protectivity in animal model

• Published in: Microbial pathogenesis Vol. 141; p. 103974
• Main Authors: Derakhshandeh, Soodabeh, Shahrokhi, Nader, Khalaj, Vahid, Habibi, Mehri, Moazzezy, Neda, Asadi Karam, Mohammad Reza, Bouzari, Saeid
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2020
• Subjects: Adhesins, Escherichia coli - genetics; Animals; Biofilms; Cell Surface Display Techniques; Cloning, Molecular; Disease Models, Animal; Escherichia coli Infections - microbiology; Escherichia coli Infections - pathology; Fimbriae Proteins - genetics; FimH; Gene Expression; Hemagglutination Tests; Lactococcus lactis; Lactococcus lactis - genetics; Mice; Peptide Library; Plasmids - genetics; Probiotic; Recombinant Proteins; Urinary tract infection; Urinary Tract Infections - microbiology; Urinary Tract Infections - pathology; Uropathogenic Escherichia coli; Uropathogenic Escherichia coli - drug effects; Uropathogenic Escherichia coli - genetics; Probiotic; Uropathogenic Escherichia coli; Lactococcus lactis; Urinary tract infection; FimH
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2020.103974

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are very common, leading to high patient morbidity and substantial medical costs. The development of non-antibiotic strategies such as food-grade lactic acid bacterium can be recognized as an attractive and safe alternative way against UTI. Here, we report the construction of Lactococcus lactis (L. lactis) strain genetically modified to produce FimH virulence factor of UPEC on the cell surface. We showed the FimH inserted into the pT1NX vector is actively synthesized on L. lactis. The L. lactis-pT1NX-FimH exhibited an auto-aggregation phenotype in liquid cultures and formed robust biofilm on abiotic surface compared to vector-only bacteria. Then, we developed protective biofilms with L. lactis strains and examined their inhibitory effect for exclusion of uropathogenic biofilm formation. In the natural protective biofilm assays, L. lactis-pT1NX-FimH resulted in significant reduction in the pathogen load when compared to the L. lactis-pT1NX. Evaluation of the colonization ability in the bladder showed that L. lactis expressing FimH survived better in the mice bladder than L. lactis harboring vector. Protection assay against UPEC infection was investigated using a UTI mouse model. L. lactis-pT1NX-FimH displayed high effectiveness in the protection of the bladder as compared to the control group after UPEC challenge. The results suggest that genetically engineered L. lactis-pT1NX-FimH can be used as a safe alternative way for control of biofilm formation in UPEC. Furthermore, the possibility of using L. lactis-pT1NX-FimH as a new promising strategy against UTIs caused by UPEC strains is proposed. •We designed a Lactococcus lactis to express FimH antigen of UPEC on the cell surface.•Recombinant L. lactis exhibited an altered new phenotype compared with L. lactis-pT1NX.•L. lactis-pT1NX-FimH survived better in the mice bladder than L. lactis-pT1NX.•L. lactis-pT1NX-FimH provided better protection against UTI than L. lactis-pT1NX.•L. lactis-pT1NX-FimH can be used as a promising construct against UTIs caused by UPEC.