Illuminating pathogen–host intimacy through optogenetics
(A) Strategic stages during the development of 2 parasitic protists (Toxoplasma gondii, Trypanosoma cruzi) and a bacterium (Chlamydia). Note that only selected features are highlighted. The shared events include invasion, proliferation, and egress. The tachyzoite stage of T. gondii actively invades host cells, reorders several organelles (not depicted for simplicity), replicates by endodyogeny in a nonfusogenic vacuole, and then exits by lysing the vacuolar and host membranes. Cyclic nucleotides (cAMP, cGMP) and ions (Ca2+, K+) play very important roles during the lytic cycle. The trypomastigote stage of T. cruzi enters the host cell by recruiting lysosomes and then escapes into cytoplasm (mediated by TcTox), where they reproduce asexually as amastigotes. Among others, Ca2+, pH, and ROS are major factors during T. cruzi infection. The EBs of Chlamydia are endocytosed into membranous vacuoles, which fuse to form an inclusion, the replicative compartment. Later on, they differentiate into larger metabolically active RBs, which replicate by binary fission before converting back to EBs. Similar to tachyzoites, Chlamydia is known to intercept/recruit many host organelles, such as Golgi, lipid droplets, and endolysosomes, probably for acquiring nutrients. Again, cAMP and cGMP, along with prokaryote-specific c-di-GMP, control the stage differentiation and STING-mediated modulation of host immunity genes, respectively. (B) Abridged lifecycle of viruses infecting a host cell. Key second messengers, ions, and metabolites potentially regulatable or detectable by optogenetic means are shown in relation to specific events during the course of infection. In particular, calcium, pH, ROS, and phosphoinositide signaling regulate a repertoire of phenomena. For additional details, please refer to the table outlining different tools, pathogens, and paradigms (Table 1). EBs, elementary bodies; RBs, reticulate bodies; ROS, reactive oxygen species; STING, stimulator of interferon genes; TcTox, T. cruzi toxin (hemolysin).