The Flagellar Motor as a Sensor Bacteria use rotation of helical flagella to propel themselves either through bulk liquid (swimming), or through a thin film of liquid on a solid surface (swarming). Chemosensory pathways normally communicate environmental information to the bidirectional rotary motor, modulating its CW/CCW bias to optimize bacterial migration towards favorable locales. These pathways are well-understood. In E. coli and other bacteria, the motor is also itself a sensory organelle, allowing bacteria to adapt to chemical signals, respond directly to increased c-di- GMP, and mechanically 'sense'a solid surface. These pathways, particularly mechanosensing, are not understood. In light of recent evidence showing that the motor restructures its stator and rotor components during both chemosensing and mechanosensing, we propose a new testable model for how the motor acts as a mechanosensor. The model identifies the rotor-stator interface as the sensory hub of the motor. We consider a finite number of structural components that could receive and transduce sensory signals from this hub. These are: MotA/B, FliG, FliM, FliL, YcgR and H-NS. The first two aims of this proposal investigate remodeling of a subset of these components under situations where the motor elicits a distinct response to two internal signals - CheY~P and c-di-GMP.
The third aim benefits from this knowledge to monitor remodeling of these components in response to mechano-signals. The insights derived from these studies are expected to eventually trace the input signal(s) at the motor to output responses that promote either motility or sessility (biofilms), both of which play critical roles i bacterial infection, surface colonization, pathogenesis, and persistence.
Motility influences the distribution of bacteria in the environment, the composition of microbial communities in biofilms, and host invasion during the establishment of beneficial and harmful associations with their hosts. Understanding the molecular mechanisms by which the flagella motor detects and responds to its environmental niche should lead to new strategies for augmenting the beneficial behaviors, and to new therapies for harmful ones.
Kim, Hyo Kyung; Harshey, Rasika M (2016) A Diguanylate Cyclase Acts as a Cell Division Inhibitor in a Two-Step Response to Reductive and Envelope Stresses. MBio 7: |
Partridge, Jonathan D; Nieto, Vincent; Harshey, Rasika M (2015) A new player at the flagellar motor: FliL controls both motor output and bias. MBio 6:e02367 |
Ariel, Gil; Rabani, Amit; Benisty, Sivan et al. (2015) Swarming bacteria migrate by Lévy Walk. Nat Commun 6:8396 |
Harshey, Rasika M; Partridge, Jonathan D (2015) Shelter in a Swarm. J Mol Biol 427:3683-94 |