Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector

Abstract

Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, <i>Anaplasma phagocytophilum</i>. 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 <i>A. phagocytophilum</i> and symbiotic <i>Sphingomonas</i> identified by metaproteomics analysis in <i>Ixodes scapularis</i> midgut showed competition between both bacteria. Consequently, <i>Sphingomonas</i> was selected for frankenbacteriosis for the control of <i>A. phagocytophilum</i> infection and transmission. The results showed that Franken <i>Sphingomonas</i> producing <i>A. phagocytophilum</i> major surface protein 4 (MSP4) mimic pathogen and reduce infection in ticks by competition and interaction with cell receptor components of infection. Franken <i>Sphingomonas</i>-MSP4 transovarial and trans-stadial transmission suggests that tick larvae with genetically modified Franken <i>Sphingomonas</i>-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.