Swarming Motility in Proteus Mirabilis: Causative Agent of UTIs
Introduction
Proteus Mirabilis belongs to the family Enterobacteriacae, which are gram negative, facultatively anaerobic rods that have the ability to grow in nutrient deficient environments. (microbio) Many species in the family are highly motile, with numerous flagella to allow for several modes of locomotion. Enterobacteriacae are also known to cause several diseases in both plants and animals. One example is the Erwinia species, which causes defects such as wilts and galls in an array of plants. (704)
P. Mirabilis is normally found in the human intestine along with other organisms composing a highly complex micro flora. They also inhabit other outside environments, and are especially prevalent in hospitals and care facilities. Interestingly, P. Mirabilis have been known to inhabit the skin and mucous of both patients and personnel working in these environments, which may be the primary vectors for pathogenecity. (emed) Metabolically, P. Mirabilis is involved in urease production, which is then used to convert urea to ammonia in the following reaction: (NH2)2CO -> 2NH3 + CO2. P. This may be one of the reasons the pathogen is so successful in colonizing the urinary tract, and cause in infection in humans.
Motility in P. Mirabilis is highly complex as they engage in several different kinds of movement depending on the specific environment they are inhabiting. Most of these movements are directly tied to the differential expression of flagellum and other factors. When in liquid environments, normal movement is facilitated by swimming. However, in more viscous and solid environments, P. Mirabilis have the ability to differentiate in elongated, multinucleated, highly flagellated cells, which then allows them to move together over solid surfaces at very high rates. (3) This activity, known as swarming, is a primary factor in the success of P. Mirabilis in causing complicated uriniary tract infections and other more serious bladder and kidney infections. (9)
UTIs as a result of P. Mirabilis are usually a secondary result of long-term catheterization in hospitals, or with individuals who have structural abnormalities. (9) The bacteria’s ability to swarm over surfaces allows them to ascend up the urethra, eventually invading the bladder and kidneys. (10) P. Mirabilis infection then leads to more complicated problems, such as bladder/kidney stones. In rare cases, P. Mirabilis is able to enter the blood stream inducing a systemic inflammatory response syndrome (SIRS), which as a mortality rate of 20%-50%. (11)
In addition to their adaptive mobile abilities, other virulence factors have deemed P. Mirabilis successful UTI causative agents. Their inhabitance in hospitals has led to several antibiotic resistance genes, making them very difficult to treat. Furthermore, their ability to forms stones in the organisms bladder/kidneys provide the bacteria with a safe haven that is impenetrable to antibiotics or the host individuals immune defenses. (9) Several methods have been developed to prevent CAUTI infection, however treating them is much more complex, as they are resistant to many of the most common types of antibiotics (penicillin, cephalosporin, tetracycline, etc.). Current research is looking into other possible routes of treating CAUTIS in an effective and simple manner, and targets the cell interesting swarming ability and other virulence factors. Understanding P. Mirabilis swarming ability in conjunction with other virulence factors may lead to greater advances in treating CAUTIs and reducing it’s prevalence in hospital settings.
Swarming Motility: a Locomotive Advantage
The ability to swarm over more viscous or even solid surfaces is restricted to only a few bacterial families: Furmicutes, alpha proteobacteia, and gama proteobacteria. P. Mirabilis falls under the gamma proteobacteria, which also include E-coli and salmonella enterica, known to cause infection in other areas of the body. These organisms, especially E-coli, have been used as models in the laboratory in understanding the mechanisms directly related to the swarming motility of bacterial colonies. (2)
Generally, vegetative bacterial cells are engaged in what is known as swimming motility, which employs the use of a rotating flagellum. (2) An individual flagellum can be thought of as a motor, that is coupled to the flow of protons across the membrane to provide energy for rotation. The motor itself is made up of two rings connect to a helical filament. (12) The direction of rotation determines the direction in which the cell swims, and is regulated by sensory inputs tied to outside environmental influence. (12). Swimming is the primary locomotive method for P. Mirabilis in liquid environments, and it differs in many ways to the little understood swarming method of movement in bacteria.
Swarming motility is mediated by several factors. The presence of a solid surface or highly viscous environments is necessary for this type of motility to occur, however it is still a mystery as to how solid surfaces may induce the several structural changes in a swarming bacterium. One of the most important changes to occur is the substantial increase of flagella along the cell surface. Bacterial cells become hyperflagellated with individual flagella arranged in bundles randomly along the surface. The bundle arrangement has been linked to increased stiffness and generation of more force to propel the cells in the necessary direction. (13). A recent study by Tuson et. al. 2012 was conducted using Proteus Mirabilis to evaluate the effectiveness of increasing flagellum density in swarming. Interestingly, Tuson et. al. 2012 found that the increased surface density of flagellum (5 times greater than that of vegetative cells) produces an increase in cell velocity when travelling through viscous medium. (14) In addition to an increase in flagellum, swarmer cells become elongated and multinucleated, although these two components were not directly linked to an increase in velocity. (2,14). Some swarming bacterium secrete what is known as a surfactants, which forms a layer over the solid surface to facilitate easier movement. This layer is usually seen as a watery substance that is found slightly before the cell front, as was observed in several studies of bacillus subtilis, another common swarmer cell. (15) Interestingly, P. Mirabilis has not been found to b a sufacant producing swarmer cell, and in fact experiences an inhibitory response when in the presence of surfactants. (16)
While swimming is possible on an individual cell basis, swarming is directed by the presence of multiple cell bodies and is facilitated as colonial movements. Swarmer cells come together and form “rafts” which are like side by side groups, solely linked by the interaction of flagella. (Microbio) Research is still being conducted to determine the necessity in raft formation in regards to swarming, however rafting is constantly observed in all bacterial swarmers, including P Mirabilis swarming over a catheter in CAUTI patients. (2)
Observing Swarming in the Laboratory
Swarming of different types of bacterial cells cultured on agar in a laboratory produces many distinct colonization patterns, and allows for a better visual understanding of the overall colonial structure of swarming bacteria. It has been found that swarming bacteria can produce a range of patterns, and that these patterns may be linked to different environmental conditions. (19).
The most well-known and irregular swarming pattern in that formed by P. Mirabilis. On solid agar plates, P. Mirabilis grow outward in a “bull’s eye pattern.” This pattern is generated by waves of swarmer cell movement, followed by differentiation into vegetative cells, and then differentiation again back into swarmer cells. Each swarming cycle/differentiation esults in the formation of a terrace, and thus the visual bull’s eye pattern. However, differentiation back into vegetative cells is not a necessary component of the bull’s eye pattern, as it was observed that Proteus Vulgarus cause the same colonial plate pattern while consistently remaining swarmer cells. (20).
Other patterns of colonial swarmer cell formation are equally interesting. Dendrite formation occurs when swarmer colonies form long thing regions emulating out from the center of inoculation on a plate. This type of pattern has been observed in Proteus aeruginosa and B. subtilitis. Recent research has indicate that the dendrite formation may be a result of multiple surfcant secretion (21). Another interesting colonial formation is that of vortices, or wandering colonies that travel in radiating packs. Studies involving Panibacillus vortex indicate that swarming motility combined with a curved cell morphology may result in this type of pattern. Swarming can also produce no pattern, in which the swarms move continuously out from the center of the plate, making an almost transparent film. Normal non-swarmed cell movement across a plate is governed by sliding motility, and produces only a slight increase in diameter from the point of inoculation. Thus, bacteria that are able to swarm produces distinct patterns when grown in the laboratory that separate them from species that are unable to swarm across surfaces.
Section 3
Include some current research in each topic, with at least one figure showing data.
Conclusion
Overall paper length should be 3,000 words, with at least 3 figures.
References
Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.
