Proteus mirabilis

Description and Significance

Proteus Mirabilis is a gram-negative, rod-shaped bacteria belonging to the enterobacteriaceae family. It is facultatively anaerobic meaning that it does not require oxygen for survival and reproduction and may even die in the presence of oxygen. Proteus Mirabilis are found free-living in moist habitats, such as water and soil. They are however mostly found in putrid meat, infusions, and abscesses. They are also found inhabiting urinary tracts of human where it is believed to cause urinary tract infections associated with formation of renal and bladder calculi, often known as bladder stones.

Genome structure

Proteus Mirabilis contains an extracytoplamic outer membrane, which is a common characteristic of other gram-negative bacteria. In addition, the outer membrane contains a lipid bilayer, lipoproteins, polysaccharides, and lipopolysaccharides. Infection depends on the interaction between the infecting organism and the host defense mechanisms. Various components of the membrane interplay with the host to determine virulence. Inoculum size is important and has a positive correlation with the risk of infection.

The genome of Proteus Mirabilis is .063 Mb long and has a G+C content of 38.88%. There is a single plasmid consisting of 36,289 nucleotides. Annotation of the genome is identified 3,685 coding sequences and seven rRNA loci. Analysis of the sequence confirmed the presence of previously identified virulence determinants, as well as a contiguous 54-kb flagellar regulon and 17 types of fimbriae. Genes encoding a potential type III secretion system were identified on a low-G+C-content genomic island containing 24 intact genes that appear to encode all components necessary to assemble a type III secretion system needle complex. In addition, the P. mirabilis HI4320 genome possesses four tandem copies of the zapE metalloprotease gene, genes encoding six putative autotransporters, an extension of the atf fimbrial operon to six genes, including an mrpJ homolog, and genes encoding at least five iron uptake mechanisms, two potential type IV secretion systems, and 16 two-component regulators.

Cell structure and metabolism

Proteus can display two different morphological and physiological forms; one is known as the swimmer cells and swarmer cells. In aqueous suspension Proteus mirabilis is found in the swimmer state, which is a small rod-like cells1 to 2 μm in length motile by 8 to 10 flagella. On contact with a surface, Proteus has the ability to convert to the swarmer state where the cell elongates dramatically to form highly flagellated filaments 20 to 80 μm in length. These cells line up in parallel to form rafts that are able to move rapidly over surfaces en masse. On semi-solid surfaces such as an agar surface, they form concentric rings of growth. This pattern is caused by the coordinated burst of swarming activity interspeded with a consolidation to the swimmer state.

An important feature of Proteus Mirabilis is their swarming motility, which is a rapid and coordinated translocation of a bacterial population across solid or semi-solid surfaces. This ability aids them in food acquisition and reproduction. It also aids the bacteria in expressing its virulence factors and invading hosts’ urothelial cells. They have the ability to produce urease, which is an enzyme that hydrolyzes urea to ammonia. In fact, Proteus Mirabilis utilizes urea and citrate. They so in order to create a suitable environment. The bacterium also produces hydrogen sulfide gas, which aid in forming clear films on growth media, which can be distinguished as growth rings.

Ecology

Proteus Mirabilis are found in moist habitats, such as water and soil. They are however mostly found in putrid meat, infusions, and abscesses. They are also found inhabiting urinary tracts of human where it is believed to cause urinary tract infections associated with formation of renal and bladder calculi, often known as bladder stones.

Pathology

Proteus Mirabilis is a significant pathogen of the urinary tract. The urinary tract infection follows a process where it starts with colonization of the bladder, which causes cystitis. Then, the infection proceeds to the kidneys, which leads to acute pyelonephritis, chronic inflammation and at last renal failure, which if left untreated, can cause death.

Proteus Mirabilis is highly virulent and contains many characteristics that aid in its pathogenicity. It fist possesses a flagella which I necessary for motility and is involved in establishing infection. It also produces urease, which is responsible for the formation of bladder and kidney stones as a result of the hydrolysis of urea to ammonia. Furthermore, the hacmolysin that the bacterium secretes is cytotoxic for urinary tract epithelial cells that it invades. The bacterium swarming motility also plays an important role in renal infections, which involve colonization of the lower urinary tract, followed by ascending migration of the bacterium. It is believed that the swarming motility is correlated with the bacterium’s ability to invade hosts’ epithelia cells, as it created rapid colonization of the bacterium.

Current Research

“Proteus Mirabilis will give up its genetic secrets at ASM meeting” ORLANDO, Fla. Scientists now have inside information to use in the fight against Proteus mirabilis a nasty bacterium that can cause kidney stones, as well as hard-to-treat urinary tract infections. Data from the first complete genome sequence for P. mirabilis, which includes at least 3,693 genes and 4.063 megabases of DNA, will be presented at the 106th general meeting of the American Society of Microbiology taking place in Orlando from May 21-25. Melanie M. Pearson, Ph.D., a research fellow in microbiology and immunology at the University of Michigan Medical School, is the first scientist to perform an in-depth analysis of the genome sequence. She will present her initial findings in an ASM poster presentation beginning at 9 a.m. on May 23. "Access to the full genome sequence will help scientists determine the virulence factors produced by the organism and learn how it causes disease," Pearson says. "Part of our goal is finding potential targets for new vaccines that could protect people from infection." "E. Coli causes urinary tract infections in otherwise healthy individuals, but P. mirabilis causes more infections in those with 'complicated' urinary tracts. In cases where stones form, the bacteria can become resistant to antibiotics," says Harry L.T. Mobley, Ph.D., professor and chair of microbiology and immunology in the U-M Medical School. "It is particularly prevalent in nursing home residents with indwelling catheters." Mobley is an expert on urease, an enzyme produced by P. mirabilis, which breaks down urea in the urinary tract, reduces the acidity of urine and leads to the formation of kidney or bladder stones. Once a stone begins to form, bacteria stick to the stone and live within its layers, where they are protected from antibiotics. When Pearson examined the genomic sequence data for Proteus mirabilis, she discovered an explanation for the bacterium's "stickiness." "This bacterium has an unusually high number of genes that encode for 15 different adherence factors or fimbriae on its surface," Pearson explains. "All these different fimbriae help the bacterium stick to bladder cells, catheters, kidney stones or each other. It's not unusual for bacteria to have several ways of attaching to surfaces, but I've never heard of one with 15 different adherence factors before." "Over the course of 20-plus years of laboratory research, we had painstakingly identified four P. mirabilis fimbriae," says Mobley. "Suddenly, here were 11 more predicted in the genome sequence data. We couldn't believe it." Pearson also discovered what she calls a "pathogenicity island" in the P. mirabilis genome made up of 24 genes that encode components of a system used to inject bacterial proteins into host cells. "Until we reviewed the sequence data, we had no idea P. mirabilis had these genes," Mobley says. "When Melanie analyzed the sequences of these 24 genes, she noticed that they have smaller amounts of two of the four nucleotides in DNA guanine and cytosine than are present in the overall genome. This implies that another bacterium contributed this little piece of DNA to P. mirabilis at some point during its evolution." In future research, Pearson will use gene micro arrays to identify the Proteus mirabilis genes that are turned on, or expressed, during the infection stage. Genes involved in the infection process will be prime targets for future vaccine development, according to Pearson, although she says that years of additional research will be needed before vaccines could be commercially available.

Reference

1. http://jmm.sgmjournals.org/cgi/reprint/49/8/725.pdf 2. http://news.bio-medicine.org/biology-news-3/Proteus-mirabilis-will-give-up-its-genetic-secrets-at-ASM-meeting-6659-2/ 3. http://jb.asm.org/cgi/content/abstract/187/19/6789 4. http://ncbi.nlm.nih.gov/pubmed/18375554 5. http://emedicine.medscape.com/article/226434-overview 6. http://www.biomedhtc.org.uk/ProteusMirabilis.htm