Francisella tularensis is one of the most infectious organisms as inhalation of a single bacterium can lead to a fatal disease referred to as tularemia. It has therefore been categorized by the Centers for Disease Control and Prevention as a Category A biodefense agent. Many seminal studies have shown that the ability of F. tularensis to replicate within macrophages is a feature of this organism during infection. Only recently we have appreciated that interactions with non-macrophages are also extremely important during infection as these cells provide a niche for immune protection, proliferation, and other unexplored roles. Although much of the work in the field of F. tularensis has focused on the intra-macrophage biology of this organism, interactions with other cell types have not been thoroughly investigated. Using both in vivo and in vitro approaches, we present strong evidence that F. tularensis invades and persists in erythrocytes. The proposed work will provide an understanding of a previously uncharacterized phenomenon by a Category A biodefense agent - namely erythrocyte invasion by F. tularensis. The two aims to investigate erythrocyte invasion by F. tularensis are: 1) To examine the molecular mechanism of F. tularensis erythrocyte invasion. 2) To determine the role of erythrocyte invasion by F. tularensis. As erythrocyte invasion of F. tularensis has not yet been described in the literature, the studies proposed here will open up a new line of research. We will investigate a potential role in pathogenesis, arthropod transmission, and disease persistence. Our work will involve evaluation of fixed blood from tularemia patients to assess the degree of erythrocyte invasion during human infection. We will also examine the mechanism by which F. tularensis erythrocyte invasion occurs, exposing novel host-microbe molecular pathways. In addition to enhancing our understanding of an important Category A biodefense agent, the research proposed may also uncover general systems implemented by diverse intracellular pathogens. The bacterial pathogen Francisella tularensis is a signficant bioterror threat. The research descibed in this proposal will make important advances toward understanding how this organism invades red blood cells. The results of this work may lead to vaccine development and potential therapeutics that alter the Francisella- erythrocytre interactions.
The bacterial pathogen Francisella tularensis is a signficant bioterror threat. The research descibed in this proposal will make important advances toward understanding how this organism invades red blood cells. The results of this work may lead to vaccine development and potential therapeutics that alter the Francisella-erythrocytre interactions.
|Zdilla, Matthew J; Russell, Michelle L; Koons, Aaron W (2018) Infraorbital foramen location in the pediatric population: A guide for infraorbital nerve block. Paediatr Anaesth 28:697-702|
|Zdilla, Matthew J; Koons, Aaron W; Russell, Michelle L et al. (2018) The Infraorbital Foramen Is Located Midway Between the Nasospinale and Jugale: Considerations for Infraorbital Nerve Block and Maxillofacial Surgery. J Craniofac Surg 29:523-527|
|Zdilla, Matthew J; Skrzat, Janusz; Kozerska, Magdalena et al. (2018) Oval Window Size and Shape: a Micro-CT Anatomical Study With Considerations for Stapes Surgery. Otol Neurotol 39:558-564|
|Zdilla, Matthew J; Russell, Michelle L; Bliss, Kaitlyn N et al. (2017) The size and shape of the foramen magnum in man. J Craniovertebr Junction Spine 8:205-221|
|Kenney, Adam; Cusick, Austin; Payne, Jessica et al. (2017) The potential for flower nectar to allow mosquito to mosquito transmission of Francisella tularensis. PLoS One 12:e0175157|
|Zdilla, Matthew J (2017) Clival canal and clival foramen development in the fetal and infant basioccipital. Childs Nerv Syst 33:1209-1216|
|Eklund, Bridget E; Mahdi, Osama; Huntley, Jason F et al. (2017) The orange spotted cockroach (Blaptica dubia, Serville 1839) is a permissive experimental host forFrancisella tularensis. Proc W Va Acad Sci 89:34-47|
|Zdilla, Matthew J; Saling, Julia R; Starkey, Leah D (2016) Zinc sulfate taste acuity reflects dietary zinc intake in males. Clin Nutr ESPEN 11:e21-e25|
|Zdilla, Matthew J; Pancake, Alex R; Lambert, H Wayne (2016) Morphometrics of the Anterior Belly and Intermediate Tendon of the Digastric Muscle: Sexual Dimorphism and Implications for Surgery. J Craniofac Surg 27:1321-6|
|Zdilla, Matthew J; Hatfield, Scott A; Mangus, Kelsey R (2016) Angular Relationship Between the Foramen Ovale and the Trigeminal Impression: Percutaneous Cannulation Trajectories for Trigeminal Neuralgia. J Craniofac Surg 27:2177-2180|
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