TABLE 1

Comparison of different model systems for studying pathogen social behavior and virulence

Category or concernData for model system (reference)
Petri dish/test tubeLive invertebrateLive mammalHuman cell or tissue cultureEx vivo pig lung culture
Example studiesReferences 2226Waxworm (27, 28), fruit fly (16), or nematode (29, 30)Usually mouse (14, 3136), occasionally other small mammals (37); also, a CF pig model exists (38)References 3941References 20, 21, 42
Chemical environmentCan be controlled to mimic CF sputum (24, 25)Not knownMouse metabolome (17) and gene expression (19) very different from humanControllable and can be made to mimic in vivo conditionsMetabolome more similar to human than a mouse is (17)
Spatial structureCan be controlled, but artificialLimitedBurn wounds, limited; lung infections, yesPossible with scaffolding or organ sectionsVery similar to human lung (18)
Immune systemNoneLimited similarity to humansLimited similarity to humansHumanVery similar to human (18) but largely lost ex vivo
Infection time scaleCan study hundreds to thousands of generationsAcute: host dies very quicklyAt best semichronic; rodent lung infections tend to be acute (days), though can sometimes last 1–4 weeks (43, 44); wound infections are usually limited to ca. 3 weeks (K. Rumbaugh, pers. commun.)aDays to weeksNot known
Large sample sizes (tens plus) possible?YesYesNo, due to cost and ethical considerationsNot usuallyYes
CostLow-mediumLowHighMedium to set up, low to runLow
Ease of methodSimple, requires only general microbiology techniquesMust learn how to inoculate but otherwise simpleRequires specialized expertise, an animal license and often a dedicated animal worker to carry out inoculationRequires expertise and dedicated lab space/equipment to minimize risk of contaminating cell linesLungs are readily obtained from commercial butchers; we developed dissection, infection, and culture techniques in ca. 3 months
Ethical considerationsNoneNoneYes—and limit sample size/infection durationMinimal (donor informed consent must be obtained)None if obtained from animals slaughtered for meat; little or no tissue is used for human consumption, so lungs are basically a waste product.
Review articlesReferences 45, 46References 37, 46, 47References 46, 48
  • a Infection duration depends on local rules governing animal welfare; e.g., in the United Kingdom, animals must be euthanized when the symptoms of infection become too severe. pers. commun., personal communication.