Many pathogenic bacteria produce toxins that are generally considered their principal virulence factor [1
]. They help to circumvent the host immune system and to promote bacterial niche establishment by disrupting host cell tissues and/or by controlling their competitors’ population [2
]. Therefore, they directly participate in bacterial replication and transmission to new hosts [3
]. Not all toxinogenic bacteria have received equal interest. In vertebrates, the most studied are those responsible for deleterious human diseases while in invertebrates, research is focused on the most virulent ones usable as biological insecticides for pest control [5
]. This led to a restricted list of pathogens to become biological models for a wide range of experiments spanning different fields of research.
Toxinogenic bacteria targeting vertebrates, especially humans, have received reasonably special attention [2
]. Toxins are generally produced during host infection and most of them have been known to interact with the immune system, either directly because immune cells are their primary target, or indirectly as the immune system reacts to toxin activity on the host’s tissues [6
]. Therefore, in vertebrates, the study of the mechanisms of response to the toxin is inseparable from the immune response to the pathogen. Such integrative approach allows deciphering the fine regulatory mechanisms underlying the evolution of host-pathogen interaction. In invertebrates, however, the adaptation to toxinogenic bacteria has been investigated by two complementary but distinct fields of research: toxinology and immunology. While toxinologists consider that toxins are the major toxic component that drives the adaptation of the insect host, mostly neglecting the role of the bacteria, immunologists rather deem that toxins are just one virulence factor among others and that the real adaptation of the insects is to the bacteria through its immune system.
Among the toxinogenic bacteria targeting insects, the spore-forming bacterium Bacillus thuringiensis
) is by far the most studied, notably because it is the most used biocontrol agent for agricultural pests and disease-carrying insects [7
is genetically indistinguishable from the two human pathogens B. cereus
and B. anthracis
(forming the B. cereus
group) and it only differs by the production during its sporulation of a crystal of invertebrate-specific toxins, whose genes are located in plasmids [8
became an unavoidable model of gram-positive bacteria due to the easiness to maintain and grow Bt
using artificial media in the lab and to produce and store its toxins as crystals, despite its very specific sequential multi-step mode of action (Figure 1
produces pore-forming toxins (PFTs) that disrupt the host’s gut (steps 1 to 6) to trigger the colonization of the hemolymph by the spores (step 7) in which they can germinate and bacteria proliferate (steps 8 to 9) in order to produce new crystals during sporulation (step 10) [10
]. The complexity and specificity of Bt
ecology and mode of infection, notably its capacity to make spores and the fact that the fitness cost of toxin production is born by the parental generation [12
], require a lot of caution when using Bt
as a model for immunological and toxinological experiments. Observations made on host response to Bt
might not be universal and readily expandable to all gram-positive bacteria or even all bacteria, as it is often done. Only considering a part of the host response, solely to the toxins, to the bacteria, or to the spores, might, therefore, lead to partial and/or erroneous conclusions.