# Regulation of the _Pseudomonas syringae_ Type III Secretion System by Host Environment Signals
## 4 Additional Global Regulators of the T3 SS in _P. syringae_
### Dual Positive and Negative Regulation of the T3 SS by Bifunctional Lon Protease  
Lon is an ATP-dependent protease and a DNA-binding transcription factor [154; 155]. As a protease, Lon suppresses T3 SS expression by degrading HrpR, thereby attenuating the expression of _hrpL_ and downstream genes in the T3 SS regulon [77; 156; 157; 158]. Lon may also suppress the T3 SS by degrading effector proteins prior to secretion, a process counteracted by interactions between T3 SS effectors and their cognate chaperones [159; 160]. As a transcription factor, Lon positively autoregulates its own expression under T3 SS-restrictive conditions by binding its own promoter [155]. Early evidence suggested Lon is expressed constitutively in _P. syringae_ as it is in other bacterial species [57; 160]. Under this model, constitutive proteolytic activity by Lon was predicted to be sufficient to suppress HrpR activation of the T3 SS under conditions where the expression of HrpR is low, such as in rich media. When _hrpR_ transcript levels rapidly spike upon exposure of _P. syringae_ to T3 SS-inducing signals, the enhanced levels of HrpR are presumably beyond the threshold of effective suppression by Lon, permitting de-repression of T3 SS [53; 60]. However, more recent studies have determined _lon_ promoter activity to be positively regulated by RbpR(-P), a T3 SS repressor, and stimulated in the presence of acetate [144; 148]. Furthermore, Lon expression is elevated in T3 SS-deficient mutants of _P. syringae_, suggesting the presence of an as-of-yet uncharacterized negative feedback loop that suppresses Lon following T3 SS activation [148].  
Regulation of the T3 SS by Lon is complex and multi-factorial, particularly given that Lon functions as a pleiotropic regulator in _P. syringae_. As a transcription factor, Lon regulates the expression of various global regulatory systems in _P. syringae_, and therefore may indirectly participate in T3 SS regulation [155]. _Lon'_ loss-of-function mutants of _P. syringae_ and other bacteria generally exhibit attenuated stress tolerance, and have also been observed to elicit a stronger immune response from host plants during infection [154; 156; 158]. While various studies have noted that Lon is necessary for full virulence of _P. syringae_ in host leaves [157; 158], it remains unclear whether this virulence defect is related to the T3 SS versus other components of the Lon regulon. In addition to its role as a negative regulator of T3 SS, Lon may also positive regulate T3 SS deployment under certain environmental conditions. Loss-of-function _Lon'_ mutants of _P. syringae_ pv. _phaseolicola_ 1448A accumulated reduced levels of T3 SS-associated gene transcripts, including upstream regulator _hrpRS_, when cultured in a T3 SS-inducing minimal medium [155; 157]. However, other studies have reported that Lon functions as a negative regulator of T3 SS under both T3 SS-restrictive and T3 SS-inducing conditions [77; 156; 158]. Whether Lon functions as a positive regulator of T3 SS in the plant environment, and/or how negative regulation by Lon may enable the fine-tuning of T3 SS deployment during host infection, has yet to be fully characterized.