deletions | additions       diff --git a/textbf_Introduction_emph_Francisella_tularensis__.tex b/textbf_Introduction_emph_Francisella_tularensis__.tex  index f83d488..0ff4eeb 100644  --- a/textbf_Introduction_emph_Francisella_tularensis__.tex  +++ b/textbf_Introduction_emph_Francisella_tularensis__.tex 
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\emph{Francisella tularensis} is a non-specific pathogen that causes lethal disease in at least 190 different species of mammals, 23 birds, 3 amphibians and 88 invertebrates (Morner and Addison, 2001). In experimental hosts, \emph{F. tularensis} invades and replicates within a wide variety of phagocytic and non-phagocytic cells (ref) and several studies have demonstrated that \emph{F. tularensis} survives engulfment by bacterivorous protists, often escaping from the food vacuole and replicating within the cytosol (Abd et al 2003; Lauriano et al 2004; others). The ability to survive intracellularly is thought to contribute to the low infectious dose of \textit{F. tularensis}, which is fewer than 10 cells in some cases (refs). Due to this high infectivity and an accompanying high rate of mortality and morbidity, \emph{F. tularensis} is of particular concern in terms of biological warfare (1, 2). An attenuated live vaccine strain (LVS) was created from a virulent isolate in the 1950s (3). [Sentence describing the attenuation]. In addition to its use as an IND human vaccine that is administered to patient populations at increased risk for tularemia (ref), the LVS strain allows for the study of \textit{F. tularensis} pathogenesis in biosafety level two laboratories (refs).   While mammalian models have historically been the main infection model for many pathogens, including \textit{F. tularensis}, non-vertebrate hosts continue to gain attention as an alternative approach for studying pathogenic microorganisms including bacteria and fungi (5). Studies In particular, studies  using the fruit fly \textit{Drosophila melanogaster} and larvae of the Greater Wax Moth \textit{Galleria mellonella} have significantly advanced our understanding of \textit{F. tularensis} pathogenesis (refs). \texit{D. melanogaster} offers powerful host genetics but it's small size makes delivering an exact dose of bacteria difficult without specialized equipment and training. Moreover, \textit{D. melanogaster} is temperature-restricted and cannot survive at typical mammalian body temperatures, making the host of limited use for analysis of pathogens with temperature-sensitive virulence patterns such as \textit{F. tularensis} (ref and fig). In contrast, \textit{G. mellonella} survives well at 37$^{\circ}$ Celsius and is large enough for confident dosing with a standard syringe. \textit{G. mellonella} larvae are also readily available in large quantities by a number of commercial suppliers. However, there are significant drawbacks to the use of \textit{G. mellonella} as well. Pupation, the process by which the larvae metamorphesize into adults, typically occurs within a short period of incubation at 37$^{\circ}$ Celsius, thereby limiting the experimental window available to researchers. In addition, lot-to-lot variability in the general health status of \textit{G. mellonella} larvae can be problematic. This latter drawback is often addressed by administering antibiotic or antifungal compounds to the insects during the course of the study, but it isn't clear the impact this may have on host immune system or on the pathogen under study. To overcome these drawbacks to the use of insects as alternative models for pathogenesis, we began to explore non-conventional host species. Our initial criteria were that an ideal insect host (a) is large enough to easily handle and inoculate with known doses of bacteria or fungi using standard gauge syringes, (b) will survive at 37$^{\circ}$ Celsius for at least two weeks, and (c) is simple and inexpensive to rear in the laboratory. ...MHC...advances to Bd. 
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