Abstract
Insects are now well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens and they are routinely used in microbial pathogenesis studies. Unfortunately, these models have yet to be incorporated into the drug development pipeline. The purpose of this work was to begin to evaluate the utility of orange spotted (Blaptica dubia) cockroaches in early antibiotic characterization. To determine whether these model hosts could exhibit mortality when infected with bacteria that are pathogenic to humans, we subjected B. dubia roaches to a range of infectious doses of Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii to identify the medial lethal dose. These results showed that lethal disease did not develop following infection of high doses of S. aureus, and A. baumannii. However, cockroaches infected with E. coli and K. pneumoniae succumbed to infection (LD50s of 5.82 × 106 and 2.58 × 106 respectively) suggesting that this model may have limitations based on pathogen specificity. However, because these cockroaches were susceptible to infection from E. coli and K. pneumoniae, we used these bacterial strains for subsequent antibiotic characterization studies. These studies suggested that β-lactam antibiotic persistence and dose was associated with reduction of hemolymph bacterial burden. Moreover, our data indicated that the reduction of bacterial CFU was directly due to the drug activity. Altogether, this work suggests that the orange-spotted cockroach infection model provides an alternative in vivo setting from which antibiotic efficacy can be evaluated.
Highlights
Insects are well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens and they are routinely used in microbial pathogenesis studies
Based on these findings and the fact that other major multi-drug resistant (MDR) bacteria, mycobacteria, and fungi are pathogenic toward other insect species, we hypothesize that a broad range of clinically relevant human pathogens will establish productive infections in orange spotted (OS) cockroaches
This showed that both E. coli and K. pneumoniae were capable of establishing lethal infections in the OS cockroaches (LD50s of 5.82 × 1 06 and 2.58 × 106 respectively; Table 1 and Table S1 in the Supplemental Material)
Summary
Insects are well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens and they are routinely used in microbial pathogenesis studies. The purpose of this work was to begin to evaluate the utility of orange spotted (Blaptica dubia) cockroaches in early antibiotic characterization To determine whether these model hosts could exhibit mortality when infected with bacteria that are pathogenic to humans, we subjected B. dubia roaches to a range of infectious doses of Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii to identify the medial lethal dose. Insects are well recognized as biologically relevant alternative hosts for dozens of mammalian pathogens (both bacteria and fungi) and they are routinely used in molecular pathogenesis studies[8,9,10,11,12,13,14,15,16,17,18,19,20,21,22] Incorporation of these models into the drug development pipeline has not yet occurred in a meaningful way. The purpose of this study is to evaluate the utility of orange spotted (OS) cockroaches (Blaptica dubia) in early antibiotic characterization
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