An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector

Yongguo Cao; Connor Rosen; Gunjan Arora; Akash Gupta; Carmen J Booth; Kristen E Murfin; Jiri Cerny; Alejandro Marin Lopez; Yu-Min Chuang; Xiaotian Tang; Utpal Pal; Aaron Ring; Sukanya Narasimhan; Erol Fikrig

doi:10.1128/IAI.00426-20

An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector

Infect Immun. 2020 Nov 16;88(12):e00426-20. doi: 10.1128/IAI.00426-20. Print 2020 Nov 16.

Authors

Yongguo Cao^{1

2}, Connor Rosen³, Gunjan Arora², Akash Gupta², Carmen J Booth⁴, Kristen E Murfin², Jiri Cerny², Alejandro Marin Lopez², Yu-Min Chuang², Xiaotian Tang², Utpal Pal⁵, Aaron Ring³, Sukanya Narasimhan⁶, Erol Fikrig^{2

7}

Affiliations

¹ Department of Clinical Veterinary Medicine, and Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China [email protected] [email protected].
² Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
³ Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
⁴ Department of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
⁵ Department of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
⁶ Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA [email protected] [email protected].
⁷ Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.

Abstract

Borrelia burgdorferi causes Lyme disease, the most common tick-transmitted illness in North America. When Ixodes scapularis feed on an infected vertebrate host, spirochetes enter the tick gut along with the bloodmeal and colonize the vector. Here, we show that a secreted tick protein, I. scapularisprotein disulfide isomerase A3 (IsPDIA3), enhances B. burgdorferi colonization of the tick gut. I. scapularis ticks in which ispdiA3 has been knocked down using RNA interference have decreased spirochete colonization of the tick gut after engorging on B. burgdorferi-infected mice. Moreover, administration of IsPDIA3 antiserum to B. burgdorferi-infected mice reduced the ability of spirochetes to colonize the tick when feeding on these animals. We show that IsPDIA3 modulates inflammatory responses at the tick bite site, potentially facilitating spirochete survival at the vector-host interface as it exits the vertebrate host to enter the tick gut. These data provide functional insights into the complex interactions between B. burgdorferi and its arthropod vector and suggest additional targets to interfere with the spirochete life cycle.

Keywords: Borrelia burgdorferi; Ixodes scapularis; colonization; protein disulfide isomerase.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Arachnid Vectors / microbiology
Borrelia burgdorferi / physiology*
Cell Line
Gene Knockdown Techniques
Humans
Immunity, Humoral
Inflammation / enzymology
Inflammation / genetics
Inflammation / metabolism
Ixodes / enzymology
Ixodes / genetics
Ixodes / metabolism*
Lyme Disease / transmission*
Membrane Proteins / metabolism
Mice
Phylogeny
Protein Disulfide-Isomerases / genetics
Protein Disulfide-Isomerases / immunology
Protein Disulfide-Isomerases / metabolism*
RNA Interference
Recombinant Proteins
Sequence Alignment
Spirochaetales / physiology

Substances

Membrane Proteins
Recombinant Proteins
Protein Disulfide-Isomerases

Abstract

Publication types

MeSH terms

Substances

Grants and funding