Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector
Lorena Mazuecos,
Pilar Alberdi,
Angélica Hernández-Jarguín,
Marinela Contreras,
Margarita Villar,
Alejandro Cabezas-Cruz,
Ladislav Simo,
Almudena González-García,
Sandra Díaz-Sánchez,
Girish Neelakanta,
Sarah I. Bonnet,
Erol Fikrig,
José de la Fuente
Affiliations
Lorena Mazuecos
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Pilar Alberdi
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Angélica Hernández-Jarguín
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Marinela Contreras
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Margarita Villar
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Alejandro Cabezas-Cruz
ANSES, INRAE, Ecole Nationale Vétérinaire d’Alfort, UMR BIPAR, Laboratoire de Santé Animale, 94700 Maisons-Alfort, France
Ladislav Simo
ANSES, INRAE, Ecole Nationale Vétérinaire d’Alfort, UMR BIPAR, Laboratoire de Santé Animale, 94700 Maisons-Alfort, France
Almudena González-García
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Sandra Díaz-Sánchez
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain
Girish Neelakanta
Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA; Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA
Sarah I. Bonnet
Functional Genetics of Infectious Diseases Unit, Institut Pasteur, CNRS UMR 2000, Université de Paris, 75015 Paris, France; Animal Health Department, INRAE, 37380 Nouzilly, France
Erol Fikrig
Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 208022, USA
José de la Fuente
SaBio. Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ronda de Toledo 12, 13005 Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA; Corresponding author
Summary: Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut showed competition between both bacteria. Consequently, Sphingomonas was selected for frankenbacteriosis for the control of A. phagocytophilum infection and transmission. The results showed that Franken Sphingomonas producing A. phagocytophilum major surface protein 4 (MSP4) mimic pathogen and reduce infection in ticks by competition and interaction with cell receptor components of infection. Franken Sphingomonas-MSP4 transovarial and trans-stadial transmission suggests that tick larvae with genetically modified Franken Sphingomonas-MSP4 could be produced in the laboratory and released in the field to compete and replace the wildtype populations with associated reduction in pathogen infection/transmission and HGA disease risks.