Francisella-arthropod vector interaction and its role in patho-adaptation to infect mammals

Abstract

Francisella tularensis is a Gram-negative, intracellular, zoonotic bacterium, and is the causative agent of tularemia with a broad host range. Arthropods such as ticks, mosquitoes, and flies maintain F. tularensis in nature by transmitting the bacteria among small mammals. While the tick is largely believed to be a biological vector of F. tularensis, transmission by mosquitoes and flies is largely believed to be mechanical on the mouthpart through interrupted feedings. However, the mechanism of infection of the vectors by F. tularensis is not well understood. Since F. tularensis has not been localized in the salivary gland of the primary human biting ticks, it is thought that bacterial transmission by ticks is through mechanical inoculation of tick feces containing F. tularensis into the skin wound. Drosophila melanogaster is an established good arthropod model for arthropod vectors of tularemia, where F. tularensis infects hemocytes, and is found in hemolymph, as seen in ticks. In addition, phagosome biogenesis and robust intracellular proliferation of F. tularensis in arthropod-derived cells are similar to that in mammalian macrophages. Furthermore, bacterial factors required for infectivity of mammals are often required for infectivity of the fly by F. tularensis. Several host factors that contribute to F. tularensis intracellular pathogenesis in D. melanogaster have been identified, and F. tularensis targets some of the evolutionarily conserved eukaryotic processes to enable intracellular survival and proliferation in evolutionarily distant hosts.

Keywords: Drosophila; F. tularensis; arthropod; tularemia; vector; virulence factor.

Figure 1

The role that arthropods play in the transmission of F. tularensis type A and B. Arthropods maintain F. tularensis infections in nature by transmitting F. tularensis between small mammals, such as rabbits and beavers in order to maintain the reservoir. Type A strain of F. tularensis is commonly transmitted by ticks and by tabanid flies, whereas Type B strain is commonly transmitted by ticks, blood-feeding mosquitoes, and by tabanid flies. In USA, bites by ticks are the predominant mode of tularemia transmission. Transmission by biting flies is observed in western regions of the USA and in Russia. Transmission by mosquitoes is observed in the northern countries of Sweden, Finland, and Russia. Classification of hosts of F. tularensis based on the subspecies of F. tularensis associated with them indicates that there are two cycles of F. tularensis: terrestrial and aquatic. Type A has a terrestrial cycle with the main reservoirs being cottontail rabbits and ticks. Type B has mainly a water-borne cycle with semi-aquatic rodents as reservoirs of infection, such as muskrats and beaver in North America, and ground voles in the former Soviet Union. Type B infections have also been associated with rivers, streams, and temporarily flooded landscapes. Asterisk (*) indicates reservoirs of F. tularensis infections.