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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM112507-01
Application #
8748746
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Reddy, Michael K
Project Start
2014-09-01
Project End
2018-04-30
Budget Start
2014-09-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
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:
Harshey, Rasika M; Partridge, Jonathan D (2015) Shelter in a Swarm. J Mol Biol 427:3683-94
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