Run-reverse-wrap! A swimming pathogen story.


Breaking down the microbiology world one bite at a time

Run-reverse-wrap! A swimming pathogen story.

Some bacteria can swim around to explore the environment. They often do this using their whip-like “tails” (flagella) to power their movements. Motility can be extremely important for their survival. Thanks to it, they can actively search for nutrients or respond to chemicals that attract or repel them through a process called chemotaxis. However, there’s also a dark side to it – bacteria can use motility to cause a more serious infection in their hosts. The swimming activity of Pseudomonas aeruginosa is one of the factors for its virulence towards humans. Researchers found how this species makes its swimming motility even more effective. But what exactly did they discover and what does it mean for us?

P. aeruginosa – our swimming micro-villain

Pseudomonas spp. are a diverse group of proteobacteria. The most notable of them is the opportunistic human pathogen, P. aeruginosa which has been explored by scientists for more than a century. P. aeruginosa is easy to culture and since manipulating its genome is not complicated, it is one of the stars of worldwide microbiology research. Although not extremely virulent, it has an extraordinary ability to grow rapidly and to form a very sturdy biofilm. However, these are not the only reasons that make it dangerous. 

Antibiotic resistance (a.k.a. the healthcare nightmare)

P. aeruginosa is the first most common cause of burn wounds infections. Moreover, it often causes typical hospital-acquired infections linked with the use of respirators (especially in cystic fibrosis patients) and catheters. Hospitals are a perfect environment for bacteria to develop antibiotic resistance. According to the recent WHO report on microbial antibiotic resistance in Europe, P. aeruginosa is one of the nine pathogens of concern in this matter. Additionally, the multidrug resistant P. aeruginosa strains kill several thousands of people each year in the U.S. alone (CDC). This makes the exploration of P. aeruginosa infection and spread mechanisms highly valuable. 

How do they move?

The spread of various bacterial infections is made easier by microbial motility, such as swimming. Many species of bacteria are flagellated, meaning they have at least one helical ‘tail’ with a rotating motor at its base, in the cell membrane. The variety in the number of flagella and the direction of their rotation determines the mode of swimming. Flagella motors can rotate clockwise (CW) or counterclockwise (CCW). This either pulls or pushes the cell – or makes it tumble, as is true in the case of E. coli which has up to ten flagella! 

P. aeruginosa flagellum at work

P. aeruginosa has just one flagellum and researchers have recently established that it provides the pathogen with a ‘run-reverse-pause’ pattern of swimming. The ‘run’ movement is powered by CCW rotation of the flagellum. It pushes the cell forwards (‘push’ mode). Subsequently, the CW rotation causes the ‘reverse’ motion which changes the swimming direction around 180°. This type of movement is also described as ‘pull’ whereby a bacterial cell is pulled towards the flagellum. However, the ‘pause’ mechanism remained unsolved for several years and the slight direction changes were considered to be caused by the Brownian motion. Until…

Figure 1: Pseudomonas flagellar motor.
Reproduced from: Bouteiller et al., 2021, Pseudomonas Flagella: Generalities and Specificities. Int. J. Mol. Sci., 22, 3337.

The wrap

The researchers from the Department of Physics at University of Science and Technology of China in Hefei decided to look closely at the ‘pause’ in the swimming behaviour of P. aeruginosa. To visualise the flagella under the fluorescence microscope, Tian et al. introduced a mutation that let them attach a fluorescent dye to the flagellin filament protein, FliC. Then, they cultured the bacteria in special 3D chambers that allow for the microscopic observation of unrestricted motility. Surprisingly, they discovered that during the swimming pause P. aeruginosa does not simply wait still, but instead it wraps its flagellum around the cell. 

Figure 2: P. aeruginosa ‘run-reverse-wrap’ swimming mode visualised using fluorescence microscopy. Here, the movement starts with ‘reverse’ (‘pull’). Microphotograph 3 depicts the ‘wrap’ (pause).
Reproduced from: Tian et al., 2022, A new mode of swimming in singly flagellated Pseudomonas aeruginosa. PNAS, 119 (14): e2120508119.

How do they even wrap it?

The researchers did not stop at simply visualising this novel movement type. They decided to decipher what makes this behaviour advantageous for P. aeruginosa. First, they discovered the physical mechanism behind the ‘wrap’. It turned out that this behaviour happens when the flagellar motor buckling becomes unstable due to the forces acting on it during the ‘pull’ mode. The ‘wrapped’ position of the flagellum is also unstable – the flagellar hook gets extremely bent during the ‘wrap’ and after some time the physical tension straightens the hook, starting the ‘push’ mode. 

Is the wrapping useful to the bacteria?

In addition to microscopic observations, the scientists measured various physical properties during the microbe’s movement, such as the swimming speed, angular change of direction and body rotational speed. Thanks to their calculations, they discovered that the wrap movement provides the bacteria with a much wider range of possibilities when it changes direction. When P. aeruginosa swims in a ‘run-reverse’ mode, the ‘pull’ ↔ ‘push’ switch makes the cell direction turn backwards (the turn angle is 150° to 180°). However, the ‘wrap’ in between these modes causes the turn angle range to get much larger (0°-180°, the peak turn angle is ca. 95°). This extension of the turn angle range is beneficial to the bacteria. Specifically, it makes their environmental explorations more efficient. But how does it work in practice?

Chemical attraction

In their last described experiment, the scientists used a number of physical properties of the cell (e.g. velocity, turn angles and flagellar thrust) in a ‘run-reverse-wrap’ mode to compute a simulated model of P. aeruginosa chemotaxis – swimming towards the chemical attractant. Using an array of data and various test conditions they calculated how fast the cell drifts towards the chemoattractant depending on whether it incorporates the ‘wrap’ in their motility. As expected, the researchers revealed that this behaviour makes P. aeruginosa better at chemotaxis. Typically, the ‘wrap’ mode allows the cell to drift towards the chemoattractant about 20% faster than when it moves without the ‘wrap’ pauses. This is the result of a broader turn angle range during the change of the movement direction.   

Is the wrap important to us? 

Overall, P. aeruginosa was shown to possess a novel type of motile behaviour – the flagellum ‘wrap’. This makes it a better explorator of its environments. For us though, it can mean several things. Firstly, strong flagellar motility in P. aeruginosa is associated with worse infection outcomes. The ‘wrap’ mode might allow the bacteria to colonise the wounds (burn wound sepsis) or lungs (pneumonia) more efficiently. Thus, in the times of antibiotic resistance problems, microbial motility might be the candidate target for novel infection treatments. It is worth noting that this could also be true for pathogens other than P. aeruginosa. Additionally, the researchers believe that the mechanism of the flagellar ‘wrap’  will inspire research in microrobotics, which is a field that can one day revolutionise medicine. Way to go, P. aeruginosa, you evil micro-rockstar! 

Link to the original post: Tian M., Wu Z., Zhang R., and Yuan J. (2022). A new mode of swimming in singly flagellated Pseudomonas aeruginosa. PNAS, 119(14)e2120508119.

Featured image: Artwork: Marta Matuszewska (author)