Trends in Parasitology
Volume 37, Issue 8, August 2021, Pages 734-746
Journal home page for Trends in Parasitology

Review
Unpacking the intricacies of Rickettsia–vector interactions

https://doi.org/10.1016/j.pt.2021.05.008Get rights and content

Highlights

  • The incidence of rickettsioses is constricted by the geographic range, host preference, and feeding habits of their vector hosts.

  • Ranging from strict vector endosymbionts to severe human pathogens, Rickettsia evolved several mechanisms fostering its dynamic life cycles (navigating between vector and vertebrate hosts).

  • A distinct vector response to Rickettsia emphasizes an intricate Rickettsia–vector relationship, but our understanding of these associations remains limited.

  • Vector competence must be an interplay between rickettsial genetics, vector biology, and feeding habits, and sympatric microbial interactions.

Although Rickettsia species are molecularly detected among a wide range of arthropods, vector competence becomes an imperative aspect of understanding the ecoepidemiology of these vector-borne diseases. The synergy between vector homeostasis and rickettsial invasion, replication, and release initiated within hours (insects) and days (ticks) permits successful transmission of rickettsiae. Uncovering the molecular interplay between rickettsiae and their vectors necessitates examining the multifaceted nature of rickettsial virulence and vector infection tolerance. Here, we highlight the biological differences between tick- and insect-borne rickettsiae and the factors facilitating the incidence of rickettsioses. Untangling the complex relationship between rickettsial genetics, vector biology, and microbial interactions is crucial in understanding the intricate association between rickettsiae and their vectors.

Section snippets

Rickettsial diversity and vector transmission

With historical significance and recognized resurgence and emergence, vector-borne rickettsial diseases affecting human health are of critical importance worldwide. In the USA, this growing trend is evident in a recent report of notifiable diseases with cases of tick-borne spotted fever rickettsiosis increasing by 23% from 2016–2018i and the recent re-emergence of flea-borne rickettsiosis within endemic areas in the USA, including California and Texas [1]. Likewise, the reappearance of

The biology of rickettsial infection in arthropods

Rickettsiae can be acquired through feeding on a bacteremic host. Alternative acquisition routes have also been described, including cofeeding with an infected arthropod on a nonrickettsemic host or transovarial transmission. Due to the host cell requirement for rickettsiae to replicate, a critical initial step in rickettsial pathogenesis is the bacterial recognition of, and attachment to, target cells. Nevertheless, the study of Rickettsiology has been hampered by the lack of genetic tools to

Tick-borne rickettsiae

Classification of the genus Rickettsia is based on genetic and biological characteristics [44]. Tick-borne, SFG rickettsiae consist of species ranging from those that cause severe and often fatal human diseases, such as Rocky Mountain spotted fever, to strict tick endosymbionts. To ensure persistence within tick populations, tick-borne rickettsiae rely on both transovarial and transstadial transmission. If imbibed in a blood meal, it is presumed that rickettsiae traverse through the midgut

Insect-borne rickettsiae

Another group of Rickettsia species, the typhus group (TG), includes pathogenic Rickettsia typhi and Rickettsia prowazekii, associated with fleas and lice, respectively. Possessing shared genetic characteristics between SFG and TG yet maintaining distinguishable biological features, the transitional group (TRG) has been more recently classified [44]. The TRG contains species with varying pathogenicity, such as R. felis, that is associated with diverse arthropod hosts (e.g., fleas, lice, mites,

Microbial interactions and vector biology

In addition to vectors' chitinous exoskeleton, resident microflora can also defend against invading microorganisms. The role of endosymbionts in the transmission of vector-borne pathogens has gained increased attention due to their ability to alter an arthropod's vectorial capacity [40,43,80]. The influence of the microbiome in altering rickettsial vector immunity and metabolism is being assessed [53]. For example, tick endosymbionts in the genera Coxiella, Rickettsia, and Francisella, which

Concluding remarks

The diversity of Rickettsia genomes and transmitting vectors provide a rich substrate to interrogate host–pathogen interactions (see Outstanding questions). Untangling the complex events in which rickettsiae can adapt to the dynamic shift between vector and vertebrate hosts will enable a better understanding of the molecular drivers associated with transmission. Limiting rickettsial disease management is the scant knowledge of the molecular and biological factors conveying rickettsial virulence

Acknowledgments

We appreciate the reviewers' thorough effort in reviewing this manuscript and apologize for any references that were omitted due to space constraints. We would also like to thank members of the Macaluso laboratory for their valuable comments. This work was supported by the National Institutes of Health (NIH) to K.R.M (AI122672 and AI077784). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Declaration of interests

The authors declare no competing interests.

Glossary

Antimicrobial peptides (AMPs)
molecules that are secreted as an innate immune response to an infection via IMD or Toll pathways. AMPs directly act against microbial agents by causing membrane disruption, inhibition of membrane protein synthesis, metabolism interference, or direct lysis. These molecules can include defensins, varisins, lysozymes, lectins, and protease inhibitors.
Antioxidant enzymes
enzymes produced to decrease the effects of ROS, including catalase, superoxide dismutases, and

References (106)

  • J.H. Kim

    Comparison of the humoral and cellular immune responses between body and head lice following bacterial challenge

    Insect Biochem. Mol. Biol.

    (2011)
  • R.V.M. Rio

    Grandeur alliances: symbiont metabolic integration and obligate arthropod hematophagy

    Trends Parasitol.

    (2016)
  • C.D. Paddock

    Rickettsialpox

  • L.S. Blanton et al.

    Flea-borne rickettsioses and rickettsiae

    Am. J. Trop. Med. Hyg.

    (2017)
  • S.M. Akram

    Rickettsia prowazekii

    StatPearls

    (2021)
  • R.F. Felsheim

    Genome sequence of the endosymbiont Rickettsia peacockii and comparison with virulent Rickettsia rickettsii: identification of virulence factors

    PLoS One

    (2009)
  • D.W. Ellison

    Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Rickettsia rickettsii Iowa

    Infect. Immun.

    (2008)
  • T.P. Driscoll

    Wholly Rickettsia! reconstructed metabolic profile of the quintessential bacterial parasite of eukaryotic cells

    mBio

    (2017)
  • C. Suwanbongkot

    Spotted fever group Rickettsia infection and transmission dynamics in Amblyomma maculatum

    Infect. Immun.

    (2019)
  • J.J. Gillespie

    Phylogeny and comparative genomics: the shifting landscape in the genomics era

  • J.H. Werren

    Biology of Wolbachia

    Annu. Rev. Entomol.

    (1997)
  • H.R. Benatti

    Maintenance of the infection by Rickettsia amblyommatis in Amblyomma cajennense sensu stricto ticks and evaluation of vector competence

    Exp. Appl. Acarol.

    (2020)
  • M.L. Levin

    Incongruent effects of two isolates of Rickettsia conorii on the survival of Rhipicephalus sanguineus ticks

    Exp. Appl. Acarol.

    (2009)
  • L.F. Houhamdi

    An experimental model of human body louse infection with Rickettsia prowazekii

    J. Infect. Dis.

    (2002)
  • J.J. Gillespie

    A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of an obligate intracellular lifestyle

    J. Bacteriol.

    (2012)
  • K. Clay

    Microbial communities and interactions in the lone star tick, Amblyomma americanum

    Mol. Ecol.

    (2008)
  • K.B. Budachetri

    An insight into the microbiome of the Amblyomma maculatum (Acari: Ixodidae)

    J. Med. Entomol.

    (2014)
  • C.D. Paddock

    Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States

    Clin. Infect. Dis.

    (2004)
  • A.N. Snellgrove

    Assessment of the pathogenicity of Rickettsia amblyommatis, Rickettsia bellii, and Rickettsia montanensis in a guinea pig model

    Vector Borne Zoonotic Dis.

    (2021)
  • E. Esteves

    Comparative analysis of infection by Rickettsia rickettsii Sheila Smith and Taiacu strains in a murine model

    Pathogens

    (2020)
  • M.B. Labruna

    Comparative susceptibility of larval stages of Amblyomma aureolatum, Amblyomma cajennense, and Rhipicephalus sanguineus to infection by Rickettsia rickettsii

    J. Med. Entomol.

    (2008)
  • C.D. Paddock

    Phylogeography of Rickettsia rickettsii genotypes associated with fatal Rocky Mountain spotted fever

    Am. J. Trop. Med. Hyg.

    (2014)
  • R. Hagen

    Conjugative transposons and their cargo genes vary across natural populations of Rickettsia buchneri infecting the tick Ixodes scapularis

    Genome Biol. Evol.

    (2018)
  • J.J. Gillespie

    Genomic diversification in strains of Rickettsia felis isolated from different arthropods

    Genome Biol. Evol.

    (2014)
  • S.P. Healy

    Effect of Rickettsia felis strain variation on infection, transmission, and fitness in the cat flea (Siphonaptera: Pulicidae)

    J. Med. Entomol.

    (2017)
  • E.E. McClure

    Engineering of obligate intracellular bacteria: progress, challenges and paradigms

    Nat. Rev. Microbiol.

    (2017)
  • P. Engstrom

    Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence

    Nat. Microbiol.

    (2019)
  • R.L. Lamason

    A streamlined method for transposon mutagenesis of Rickettsia parkeri yields numerous mutations that impact infection

    PLoS One

    (2018)
  • Z.M. Liu

    Mariner-based transposon mutagenesis of Rickettsia prowazekii

    Appl. Environ. Microbiol.

    (2007)
  • A. Osterloh

    Immune response against rickettsiae: lessons from murine infection models

    Med. Microbiol. Immunol.

    (2017)
  • J. Salje

    Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle

    Nat. Rev. Microbiol.

    (2021)
  • E.K. Harris

    The role of Sca2 and RickA in the dissemination of Rickettsia parkeri in Amblyomma maculatum

    Infect. Immun.

    (2018)
  • J.J. Gillespie

    Louse- and flea-borne rickettsioses: biological and genomic analyses

    Vet. Res.

    (2009)
  • K.L. Rosche

    Arthropods under pressure: stress responses and immunity at the pathogen–vector interface

    Front. Immunol.

    (2020)
  • X. Yang

    A novel tick protein supports integrity of gut peritrophic matrix impacting existence of gut microbiome and Lyme disease pathogens

    Cell. Microbiol.

    (2021)
  • D.E. Sonenshine et al.

    Biology of Ticks

    (2014)
  • J.A. Vaughan et al.

    Patterns of erythrocyte digestion by bloodsucking insects: constraints on vector competence

    J. Med. Entomol.

    (1993)
  • A.C. Fogaca

    Tick immune system: what is known, the interconnections, the gaps, and the challenges

    Front. Immunol.

    (2021)
  • G.D. Baldridge

    Susceptibility of Rickettsia monacensis and Rickettsia peacockii to Cecropin A, Ceratotoxin A, and lysozyme

    Curr. Microbiol.

    (2005)
  • J. de la Fuente

    Tick–pathogen interactions and vector competence: identification of molecular drivers for tick-borne diseases

    Front. Cell. Infect. Microbiol.

    (2017)
  • Cited by (0)

    View full text