Fifty Ways To Inhibit Motility via Cyclic Di-GMP: the Emerging Pseudomonas aeruginosa Swarming Story Linda L. McCarter, a Mark Gomelsky b Department of Microbiology, University of Iowa, Iowa City, Iowa, USA a ; Department of Molecular Biology, University of Wyoming, Laramie, Wyoming, USA b There are numerous ways by which cyclic dimeric GMP (c-di-GMP) inhibits motility. Kuchma et al. (S. L. Kuchma, N. J. Delalez, L. M. Filkins, E. A. Snavely, J. P. Armitage, and G. A. O’Toole, J. Bacteriol. 197:420 – 430, 2015, http://dx.doi.org/10.1128/JB.02130 -14) offer a new, previously unseen way of swarming motility inhibition in Pseudomonas aeruginosa PA14. This bacterium pos- sesses a single flagellum with one rotor and two sets of stators, only one of which can provide torque for swarming. The research- ers discovered that elevated levels of c-di-GMP inhibit swarming by skewing stator selection in favor of the nonfunctional, “bad” stators. A seemingly bizarre way to inhibit motility. Since its discov- ery in the 1980s (1) and its very humble beginnings, cyclic dimeric GMP (c-di-GMP) has risen to the limelight of bacterial signal transduction as one of the most common bacterial second messengers (2). While c-di-GMP signaling pathways affect vari- ous aspects of bacterial physiology and metabolism, perhaps the best-known processes are the transition of motile bacteria to the nonmotile, sessile state and the regulation of biofilm formation. c-di-GMP inhibits motility via many mechanisms, most of which remain poorly understood. The study by the O’Toole and Armit- age groups in this issue of the Journal of Bacteriology offers a new, previously unseen twist on c-di-GMP-dependent swarming mo- tility control in Pseudomonas aeruginosa PA14 (3). This bacterium possesses dual flagellar motors that function under different con- ditions. The researchers discovered that elevated levels of c-di- GMP stop swarming by affecting stator selection. Stators are the proton-conducting membrane channels that generate torque, which powers flagellar rotation. Removing high-functioning sta- tors and allowing the “bad” ones that do not support swarming motility to stay seems like a very strange way to stop. To put this study in perspective, let us take a closer look at the structures and functions of flagella, at the various stator arrangements, and at the ways and means by which c-di-GMP is known to affect flagellar functions. Diversity in flagellar organization and function. Flagellar propelled motility is a very effective and widespread mode of mi- crobial locomotion. The types of flagella and their arrangement on the cell body and the motors, the energy sources, and the chemot- actic navigation systems found in microbes are amazingly diverse (4). Flagella can be single polar, multiple tufted polar, sheathed polar, peritrichous (around), lateral (near but not at a pole), and even periplasmic. The same flagella often propel bacteria in low- viscosity and relatively high-viscosity media, but this is possible only up to a point (5). Under conditions of high load, i.e., very high viscosity or on a solid surface, flagellar performance dimin- ishes. To aid motility, some bacteria employ performance-en- hancing stratagems. For example, representatives from Aeromo- nas, Azospirillum, Shewanella, and Vibrio use a distinct second flagellar system optimized for swarming over a surface, whereas Proteus greatly increases flagellar numbers to permit surface trans- location (reviewed in references 6 and 7). Yet other bacteria ele- gantly engage new motor parts to accommodate changing de- mands (reviewed in reference 8). Flagella are turned by a rotary motor (reviewed in reference 9), which couples ion flux through the cell membrane to motor rota- tion. The motor proteins designated MotA and MotB form the stator, which is the ion-conducting channel complex that gener- ates the torque. It can be anchored to the cell wall via MotB, which possesses a peptidoglycan-binding domain. Tethering is dynamic, not permanent, and there is rapid turnover of MotB in the motor (10). The stator interacts with the rotor/switch element, which is made of the FliG, FliM, and FliN proteins. Ion flow through the MotA 4 B 2 complex is tightly coupled to rotation via specific elec- trostatic interactions between the MotA protein of the stator and the FliG protein of the rotor. Most flagellar motors are reversible rotary machines, and switching of the direction of rotation or pausing is key to responding in changes in environmental condi- tions via chemotaxis and adaptation (reviewed in reference 11). The rotor is surrounded by multiple stators, which appear like studs encircling the rotor in freeze fracture and electron cryoto- mography micrographs (12, 13)(Fig. 1). The number of stators engaged is dynamic; a maximally functioning motor has 11 units (14). For the Vibrio Na + -driven motor, PomAB stator local- ization at the rotor is dependent on Na + concentration and ion flux (15). In Escherichia coli, a single torque generator rotates the flagellum under conditions of low load, but as load increases, the number of stators recruited to the motor increases (16, 17). Some- times dual stators power a single rotor, and each stator set can have specific contributions. For example, the H + -type motor of B. sub- tilis enables fast swimming speeds, but input by its Na + -type mo- Accepted manuscript posted online 1 December 2014 Citation McCarter LL, Gomelsky M. 2015. Fifty ways to inhibit motility via cyclic di-GMP: the emerging Pseudomonas aeruginosa swarming story. J Bacteriol 197: 406 – 409. doi:10.1128/JB.02483-14. Editor: T. J. Silhavy Address correspondence to Linda L. McCarter, linda-mccarter@uiowa.edu, or Mark Gomelsky, gomelsky@uwyo.edu. Copyright © 2015, American Society for Microbiology. All Rights Reserved. doi:10.1128/JB.02483-14 The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM. COMMENTARY 406 jb.asm.org February 2015 Volume 197 Number 3 Journal of Bacteriology Downloaded from https://journals.asm.org/journal/jb on 12 November 2021 by 3.236.146.4.