# Regulation of the _Pseudomonas syringae_ Type III Secretion System by Host Environment Signals
## 5 Conclusions and Future Directions  
The deployment of the T3 SS by _P. syringae_ is a complex and environmentally attuned process. Given that the initial hours of _P. syringae_ infection critically determine the eventual outcome of disease, the elucidation of these early host-pathogen signaling events is fundamental to understanding _P. syringae_ pathogenesis as a whole. Key points highlighted in this review include:  
* _P. syringae_ rapidly deploys the T3 SS during the initial hours of plant host infection, and primarily relies on the T3 SS to establish growth within the host apoplast. T3 SS deployment may be negatively regulated in later stages of infection, possibly as a means to maximize fitness in the host environment. * T3 SS expression by _P. syringae_ is induced by specific organic acids and amino acids that are abundant in the plant environment. These T3 SS-inducing plant metabolites require the presence of a simple sugar such as fructose for maximal bioactivity, suggesting _P. syringae_ coordinates T3 SS deployment by sensing multiple distinct host signals. * The abundance of T3 SS-inducing metabolites in the host environment is genetically regulated by the plant host and significantly impacts the progression of _P. syringae_ disease, as evidenced by the enhanced disease resistance phenotypes of the _mkp1_ mutant of Arabidopsis. * AauSR, a two-component system in _P. syringae_ associated with the uptake of acidic amino acids by the ABC transporter AatQMP, directly regulates the expression of T3 SS genes in response to host-derived aspartic acid and glutamic acid signals. Additional proteins including RhpSR, CvsSR and SetA may also function as sensors for host signals leading to T3 SS regulation. However, the specific signal(s) these proteins detect and the means by which these various response pathways interact to synergistically regulate the T3 SS are unknown. Despite significant progress in identifying T3 SS-inducing signals and their putative receptors, many aspects of T3 SS regulation during host infection are poorly understood. Important questions remaining include:
* Do all _P. syringae_ detect and respond to the same T3 SS-inducing metabolites? Molecular studies of T3 SS induction have so far been limited to a small number of _P. syringae_ strains. Broadening future analyses to include additional strains that represent the diversity of the _P. syringae_ species complex will be necessary to fully evaluate the conservation of host-perception mechanisms. * How many distinct host signals does a single strain of _P. syringae_ respond to? Mutants lacking putative host signal receptors (e.g., AauSR, SetA) are only partially attenuated in virulence, suggesting that multiple input signals may additively or synergistically contribute to T3 SS induction in _P. syringae_. * Multiple regulatory systems in _P. syringae_ are known to influence T3 SS dynamics--how do these distinct pathways intersect and converge on T3 SS regulation? A newly published analysis of gene regulatory networks in _P. syringae_ (termed PSRnet) indicates that complex crosstalk occurs between multiple known virulence regulators [198]. * At what point(s) during _P. syringae_ infection is T3 SS deployment repressed, and why? While evidence suggests that T3 SS expression may be downregulated in _P. syringae_ on the leaf surface and/or during later stages of apoplast infection, the mechanisms responsible for T3 SS repression during host infection are not fully understood. Moreover, the role T3 SS repression may play in _P. syringae_ virulence and life cycle remains ambiguous. Further elucidation of how the T3 SS is co-regulated with other virulence-related processes in _P. syringae_, as well as the impact of T3 SS deployment on bacterial cell homeostasis and growth, may help to elucidate the potential benefits of T3 SS repression. * How is deployment of the T3 SS spatially regulated within the host environment? Additionally, how is T3 SS deployment regulated on the population level during _P. syringae_ infection?