Unpacking the intricacies of Rickettsia-vector interactions

Abstract

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.

Keywords: Rickettsia; vector; vector transmission; vector–pathogen interactions.

Figure 1.. Attributes of rickettsiae guiding the interaction within arthropod vectors.

Upon early infection within their vector hosts, rickettsiae must modulate the arthropod immune response to facilitate survival, cellular invasion, and replication. Due to their intracellular lifestyle, all rickettsiae must sequester host metabolites to ensure replication. Distinguishing factors proposed that enhance virulence among rickettsial species include genome reduction or gene regulation [3]; the expression of Omps involved in adhesion, invasion, or motility [4, 5]; metabolic reprogramming [6, 7]; and increased bacterial loads within vector tissues, such as salivary glands [8]. Red depicts factors indicative of pathogens, and green represents attributes of endosymbionts. Pathogenic Rickettsia spp. tend to favor horizontal transmission due to potential detrimental effects on fecundity or fitness of their arthropod hosts; therefore, decreasing the efficiency of vertical transmission [11, 12]. However, increasing reports have incriminated rickettsial endosymbionts as causes of disease in vertebrates inferring their ability also to be horizontally transmitted [19]. A defining characteristic of endosymbionts is their high-efficiency rates of vertical transmission within vector populations [11], which is facilitated by their ability to provide nutritional symbiosis to their vector hosts [9]. Additionally, restrictions such as truncated Omps are thought to play a role in tissue dissemination, limiting rickettsial spread to salivary glands [4]. Confounding the virulence spectrum is the presence of plasmids among Rickettsia species, while common among most rickettsial endosymbionts, species known to be pathogenic to humans also possess these genetic elements [3, 44]. Thus, their function remains unknown. Abbreviations: Omps, outer membrane proteins.

Figure 2, Key Figure.. Transmission mechanisms of rickettsiae.

After arthropods imbibe an infectious bloodmeal, rickettsiae encounter the MG of ticks, lice, or fleas where recognition causes the secretion of various soluble effectors, such as AMPs (A, G), ROS (A, D, G), serine proteases (G), and serpins (G) into the MG lumen. As rickettsiae attach to unknown receptors and invade MG epithelial cells, interactions with resident endosymbionts occur (A, D, H). The rapid digestion of host cells in insect vectors such as lice and fleas prompt efficient attachment to MG epithelial cells and internalization of rickettsiae to avoid destruction by proteolytic compounds (D, G). For tick-borne rickettsiae, it is presumed that rickettsiae are internalized by receptor-mediated endocytosis of MG epithelial cells initiated by the digestive process of Hb (B). Tick-borne rickettsiae spread cell-to-cell, ultimately traversing to the H, where they gain access to both the SG and OV for transmission (C). As insect-borne rickettsiae replicate, host cell lysis occurs, releasing rickettsiae back into the MG lumen enabling transmission to vertebrate hosts through the inoculation of infectious feces in abrasions of the skin (E, I). Although increased MG epithelial permeability causes mortality of lice vectors (F), flea-borne rickettsiae can navigate to the H, disseminating to SG and OV for transmission (I). Green and orange arrows represent arthropod/vertical and vertebrate/horizontal transmission, respectively. Abbreviations: AMPs, antimicrobial peptides; H, hemocoel; Hb, hemoglobin; MG, midgut; OV, ovaries; RBCs, red blood cells; ROS, reactive oxygen species; serpins, serine protease inhibitors; SG, salivary gland.