Nathan edited section_Discussion_textit_F_tularensis__.tex  over 8 years ago

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Temperature is known to regulate expression of \textit{F. tularensis} virulence factors \cite{18842136}. One of the advantages of insect systems in comparison with mammalian hosts is the ability to experimentally manipulate the temperature at which the host-pathogen interaction occurs. When we varied the temperature of incubation, we saw that as temperature decreased, so did \textit{F. tularensis} LVS virulence (Figure 2, Table 1). This observation raises the intriguing possibility to collect gene expression data from \textit{F. tularensis} LVS growing at different temperatures \textit{in vivo} and comparing the resulting patterns with cells grown at different temperatures \textit{in vitro}.   Host immune function is not static,but  rather it varies, sometimes dramatically, often varies dramatically  across developmental stages. \textcolor{red}{RED} red stages \cite{25730277}. We therefor sought to determine if OS cockroach susceptibility to \textit{F. tularensis} LVS varied by developmental stage. We determined the killing kinetics and LD_50s of \textit{F. tularensis} LVS against late-stage juvenile, adult female, and adult male OS cockroaches. The susceptibility pattern of juveniles (which we used for all other experiments reported here) and adult females were highly similar. But interestingly, adult males showed enhanced susceptibility in comparison, with a shorter median time to death (Figure 4) and lower LD_50 (Table 1). The reason for this difference is currently unknown and future experiments aimed at uncovering the mechanistic differences in immune responses between these groups could identify important anti-\textit{F. tularensis} host pathways.  Mutants.  In vivo growth.  Antibiotic rescue.  The results presented here indicate that the OS cockroach is susceptible to infection by \textit{F. tularensis} LVS and that full virulence requires environmental (temperature) and genetic factors known to contribute to \textit{Francisella spp} pathogenesis in mammals. Increasing doses of bacteria led to decreases in the percentage of cockroaches that survived challenge and a decrease in the time to death (Figure 1). \textit{F. tularensis} virulence factors induced by growth at 37°C are known to be important for virulence in mammalian hosts (refs). We have observed that pathogenesis in the OS cockroach model is also temperature-dependent, indicating that similar virulence factors may be involved. Moreover, four mutant strains devoid of specific virulence factors required for pathogenesis in mice were severely attenuated in OS cockroaches (Table 1).