AUTHOR=Cull Benjamin , Burkhardt Nicole Y. , Wang Xin-Ru , Thorpe Cody J. , Oliver Jonathan D. , Kurtti Timothy J. , Munderloh Ulrike G. 

TITLE=The Ixodes scapularis Symbiont Rickettsia buchneri Inhibits Growth of Pathogenic Rickettsiaceae in Tick Cells: Implications for Vector Competence

JOURNAL=Frontiers in Veterinary Science

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2021.748427

DOI=10.3389/fvets.2021.748427

ISSN=2297-1769

ABSTRACT=<p><italic>Ixodes scapularis</italic> is the primary vector of tick-borne pathogens in North America but notably does not transmit pathogenic <italic>Rickettsia</italic> species. This tick harbors the transovarially transmitted endosymbiont <italic>Rickettsia buchneri</italic>, which is widespread in <italic>I. scapularis</italic> populations, suggesting that it confers a selective advantage for tick survival such as providing essential nutrients. The <italic>R. buchneri</italic> genome includes genes with similarity to those involved in antibiotic synthesis. There are two gene clusters not found in other Rickettsiaceae, raising the possibility that these may be involved in excluding pathogenic bacteria from the tick. This study explored whether the <italic>R. buchneri</italic> antibiotic genes might exert antibiotic effects on pathogens associated with <italic>I. scapularis</italic>. Markedly reduced infectivity and replication of the tick-borne pathogens <italic>Anaplasma phagocytophilum, R. monacensis</italic>, and <italic>R. parkeri</italic> were observed in IRE11 tick cells hosting <italic>R. buchneri</italic>. Using a fluorescent plate reader assay to follow infection dynamics revealed that the presence of <italic>R. buchneri</italic> in tick cells, even at low infection rates, inhibited the growth of <italic>R. parkeri</italic> by 86–100% relative to <italic>R. buchneri</italic>-free cells. In contrast, presence of the low-pathogenic species <italic>R. amblyommatis</italic> or the endosymbiont <italic>R. peacockii</italic> only partially reduced the infection and replication of <italic>R. parkeri</italic>. Addition of host-cell free <italic>R. buchneri</italic>, cell lysate of <italic>R. buchneri-</italic>infected IRE11, or supernatant from <italic>R. buchneri-</italic>infected IRE11 cultures had no effect on <italic>R. parkeri</italic> infection and replication in IRE11, nor did these treatments show any antibiotic effect against non-obligate intracellular bacteria <italic>E. coli</italic> and <italic>S. aureus</italic>. However, lysate from <italic>R. buchneri-</italic>infected IRE11 challenged with <italic>R. parkeri</italic> showed some inhibitory effect on <italic>R. parkeri</italic> infection of treated IRE11, suggesting that challenge by pathogenic rickettsiae may induce the antibiotic effect of <italic>R. buchneri</italic>. This research suggests a potential role of the endosymbiont in preventing other rickettsiae from colonizing <italic>I. scapularis</italic> and/or being transmitted transovarially. The confirmation that the observed inhibition is linked to <italic>R. buchneri</italic>'s antibiotic clusters requires further investigation but could have important implications for our understanding of rickettsial competition and vector competence of <italic>I. scapularis</italic> for rickettsiae.</p>