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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02665

A novel Single Domain Antibody Targeting FliC flagellin of Salmonella enterica for effective inhibition of host cell invasion

 Jennifer Huen1, 2, Zhun Yan1,  Jeremy Iwashkiw1, Shraddha Dubey1,  Maria C. Gimenez2,  Maria E. Ortiz2, Saumil V. Patel1, Michael D. Jones1, Ali Riazi1,  Mauricio Terebiznik2*,  Saeid Babaei1* and  Dea Shahinas1*
  • 1AbCelex Technologies Inc., Canada
  • 2University of Toronto Scarborough, Canada

The enteric pathogen, Salmonella enterica is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies (sdAbs), the smallest antibody fragments that retain antigen binding specificity and affinity, are derived from variable heavy-chain only fragments (VHH) of camelid heavy-chain-only immunoglobulins. SdAbs typically contain a single disulfide bond simplifying recombinant protein production in microbial systems. These factors make sdAbs ideally suited for the development of effective anti-bacterial therapeutics. To this end, we generated an anti-Salmonella VHH library from which we screened for high affinity sdAbs. We present a novel sdAb (Abi-Se07) that targets the Salmonella virulence factor, FliC, required for bacterial motility and invasion of host cells. We demonstrate that Abi-Se07 bound FliC with a KD of 16.2 ± 0.1 nM. In addition, Abi-Se07 exhibited cross-serovar binding to both whole cells of S. enterica serovar Typhimurium, Heidelberg, and Hadar. Abi-Se07 significantly inhibited bacterial motility and significantly reduced S. enterica colonization in a more native environment of chicken jejunum epithelium. Taken together, we have identified a novel anti-Salmonella sdAb and discuss future efforts toward therapeutic development.

Keywords: single domain antibody (sdAb), Salmonella enterica, Food Safety, pathogen, Bacterial motility, bacterial invasion, binding affinity

Received: 22 Feb 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Huen, Yan, Iwashkiw, Dubey, Gimenez, Ortiz, Patel, Jones, Riazi, Terebiznik, Babaei and Shahinas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Mauricio Terebiznik, University of Toronto Scarborough, Toronto, M1C 1A4, Ontario, Canada, terebiznik@utsc.utoronto.ca
Dr. Saeid Babaei, AbCelex Technologies Inc., Mississauga, L4V 1T4, Ontario, Canada, sbabaei@abcelex.com
Dr. Dea Shahinas, AbCelex Technologies Inc., Mississauga, L4V 1T4, Ontario, Canada, dea.shahinas@alum.utoronto.ca