Mechanisms to achieve this target many components of the host cell death signalling pathways (reviewed in [39]). Manipulation of PCD by bacterial pathogens of animals and plants Bacterial pathogens of animals and plants can exert a pro-apoptotic effect Selleck Alvocidib on cells, or they can block apoptosis [40].Legionella pneumophila, the Legionnaires’ disease bacterium, induces host PCD as part of its pathogenic strategy through activation of the

mitochondrial apoptosis pathway, including activation of caspases, BAX activation, and release of cytochromec[41].Salmonella entericainduces apoptosis in intestinal cells, but in macrophages it induces pyroptosis, a recently described

caspase-1-dependent PCD pathway distinct from apoptosis [42], and for which a GO term has not yet been created.Mycobacterium tuberculosis, the causative agent of tuberculosis, induces macrophage Mdm2 antagonist apoptosis in humans by a tumour necrosis factor (TNF)-α-dependent mechanism. Induction of apoptosis byM. tuberculosisoccurs in a strain-dependent manner [43], underscoring the variability of symbiont-host interactions. Annotating characterized proteins fromL. pneumophila,S. enterica, orM. tuberculosiswith “”GO: 0052151 positive regulation by symbiont of host apoptosis”" would facilitate useful comparison (Figure2). In contrast,Rickettsia rickettsiican block apoptosis via activation of the

transcription factor nuclear factor kappa B (NF-κB) pathway [40]. To describe blockage of host apoptosis, “”GO: 0033668 negative regulation by symbiont of host apoptosis”", a child of “”GO: 0052150 modulation by symbiont of host apoptosis”" (both shown in Figure2), could be used. Many bacterial pathogens of plants, includingPseudomonas syringaepathovars,Ralstonia solanacearum, Xanthomonasspp., andErwiniaspp., secrete AZD2014 molecular weight effector proteins that can affect host cell defense signalling including the HR. Some are injected directly via type III or type IV fantofarone secretion machinery into the host cell (reviewed in [44] and in this supplement [36,37,45]). Here, and in a following section describing necrotrophic fungi and bacteria, the roles of effectors in modulating PCD duringP. syringaeandPectobacterium carotovorum(formerlyErwinia carotovora) infection are summarized briefly. Many effectors produced byP. syringaecan either elicit or suppress the HR depending on the effector andR-gene repertoires of the interacting strains and plants [46–49], and thusR-gene mediated resistance is a practical approach to the protection of crops againstP. syringae[50]. To annotate such effector proteins, one could use “”GO: 0034053 modulation by symbiont of host defense-related programmed cell death”", or either of its child terms, e.g.