Nathan edited subsection_Antibiotic_rescue_of_infected__.tex  over 8 years ago

Commit id: e89719b61d54fba7433c3bc2e5ae76e637fe243d

deletions | additions      

       

\subsection{Antibiotic rescue of infected OS cockroaches}  To explore whether OS cockroaches may be useful to model post-infection antibiotic treatment following \textit{F. tularensis} infection, we infected cockroaches with a high dose (3.4 x 10^{6} CFU) of \textit{F. tularensis} LVS by intrahemocoel injection and then administered antibiotics either by injection or by controlled feeding (\textbf{Figure 6}). As controls, cockroaches were either orally fed a sucrose solution or injected with PBS (neither contained antibiotics). All control cockroaches (no antibiotics) died by day 7 post-infection (Figure 7). (\textbf{Figure 7A}).  Doxycycline, an antibiotic known to absorb well through mucus membranes, effectively prevented cockroach death when delivered by either route (statistics???; Figure 7). However, streptomycin and gentamicin, (\textbf{Figure 7B}, p<0.0001). Ciprofloxacin,  which have poor oral bioavailbility in mammals, only were effective at preventing cockroach death when injected directly into the hemocoel (80 percent survival with streptomycin [p=0.00199]; 90 percent survival with gentamicin [p<0.001]; Figure 7). Ciprofloxacin is also readily absorbed orally,  failed to fully rescue OS cockroaches from LVS-induced death at the dose administered (1 ug per roach; 60 percent survival by ciprofloxacin injection; 50 percent survival by ciprofloxacin feeding; Figure 7), \textbf{Figure 7C}),  which may be due to differences in drug pharmacokinetics between insects and mammals. Streptomycin and gentamicin, which have poor oral bioavailbility in mammals, were effective at preventing cockroach death when injected directly into the hemocoel (80 percent survival with streptomycin [p=0.00199]; 90 percent survival with gentamicin [p<0.001]) but not not when delivered by forced feeding (\textbf{Figure 7D and 7E}).  Finally, Resazurin, a small-molecule dye that has anti-\textit{F. tularensis} activity \textit{in vitro} \cite{24367766}, failed to protect OS cockroaches from infection (no survival by either delivery route; Figure 7). \textbf{Figure 7F}).