Ticks and Tularemia: Do We Know What We Don't Know?

Francisella tularensis, the causative agent of the zoonotic disease tularemia, is characterized by high morbidity and mortality rates in over 190 different mammalian species, including humans. Based on its low infectious dose, multiple routes of infection, and ability to induce rapid and lethal disease, F. tularensis has been recognized as a severe public health threat—being designated as a NIH Category A Priority Pathogen and a CDC Tier 1 Select Agent. Despite concerns over its use as a bioweapon, most U.S. tularemia cases are tick-mediated and ticks are believed to be the major environmental reservoir for F. tularensis in the U.S. The American dog tick (Dermacentor variabilis) has been reported to be the primary tick vector for F. tularensis, but the lone star tick (Amblyomma americanum) and other tick species also have been shown to harbor F. tularensis. This review highlights what is known, not known, and is debated, about the roles of different tick species as environmental reservoirs and transmission vectors for a variety of F. tularensis genotypes/strains

Tick Extracellular Vesicles Enable Arthropod Feeding and Promote Distinct Outcomes of Bacterial Infection

Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases

Pathways between Primary Production and Fisheries Yields of Large Marine Ecosystems

The shift in marine resource management from a compartmentalized approach of dealing with resources on a species basis to an approach based on management of spatially defined ecosystems requires an accurate accounting of energy flow. The flow of energy from primary production through the food web will ultimately limit upper trophic-level fishery yields. In this work, we examine the relationship between yield and several metrics including net primary production, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production. We also evaluate the relationship between yield and two additional rate measures that describe the export of energy from the pelagic food web, particle export flux and mesozooplankton productivity. We found primary production is a poor predictor of global fishery yields for a sample of 52 large marine ecosystems. However, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production were positively associated with yields. The latter two measures provide greater mechanistic insight into factors controlling fishery production than chlorophyll concentration alone. Particle export flux and mesozooplankton productivity were also significantly related to yield on a global basis. Collectively, our analyses suggest that factors related to the export of energy from pelagic food webs are critical to defining patterns of fishery yields. Such trophic patterns are associated with temperature and latitude and hence greater yields are associated with colder, high latitude ecosystems

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Mechanisms Affecting the Acquisition, Persistence and Transmission of Francisella tularensis in Ticks

Over 600,000 vector-borne disease cases were reported in the United States (U.S.) in the past 13 years, of which more than three-quarters were tick-borne diseases. Although Lyme disease accounts for the majority of tick-borne disease cases in the U.S., tularemia cases have been increasing over the past decade, with >220 cases reported yearly. However, when comparing Borrelia burgdorferi (causative agent of Lyme disease) and Francisella tularensis (causative agent of tularemia), the low infectious dose (<10 bacteria), high morbidity and mortality rates, and potential transmission of tularemia by multiple tick vectors have raised national concerns about future tularemia outbreaks. Despite these concerns, little is known about how F. tularensis is acquired by, persists in, or is transmitted by ticks. Moreover, the role of one or more tick vectors in transmitting F. tularensis to humans remains a major question. Finally, virtually no studies have examined how F. tularensis adapts to life in the tick (vs. the mammalian host), how tick endosymbionts affect F. tularensis infections, or whether other factors (e.g., tick immunity) impact the ability of F. tularensis to infect ticks. This review will assess our current understanding of each of these issues and will offer a framework for future studies, which could help us better understand tularemia and other tick-borne diseases

Characterization of Francisella tularensis Outer Membrane Proteins

Francisella tularensis is a gram-negative coccobacillus that is capable of causing severe, fatal disease in a number of mammalian species, including humans. Little is known about the proteins that are surface exposed on the outer membrane (OM) of F. tularensis, yet identification of such proteins is potentially fundamental to understanding the initial infection process, intracellular survival, virulence, immune evasion and, ultimately, vaccine development. To facilitate the identification of putative F. tularensis outer membrane proteins (OMPs), the genomes of both the type A strain (Schu S4) and type B strain (LVS) were subjected to six bioinformatic analyses for OMP signatures. Compilation of the bioinformatic predictions highlighted 16 putative OMPs, which were cloned and expressed for the generation of polyclonal antisera. Total membranes were extracted from both Schu S4 and LVS by spheroplasting and osmotic lysis, followed by sucrose density gradient centrifugation, which separated OMs from cytoplasmic (inner) membrane and other cellular compartments. Validation of OM separation and enrichment was confirmed by probing sucrose gradient fractions with antibodies to putative OMPs and inner membrane proteins. F. tularensis OMs typically migrated in sucrose gradients between densities of 1.17 and 1.20 g/ml, which differed from densities typically observed for other gram-negative bacteria (1.21 to 1.24 g/ml). Finally, the identities of immunogenic proteins were determined by separation on two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analysis. This is the first report of a direct method for F. tularensis OM isolation that, in combination with computational predictions, offers a more comprehensive approach for the characterization of F. tularensis OMPs