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One fear that pervades college campuses, child care facilties, and other public places is the risk of contracting a deadly disease. One such disease, bacterial meningitis, is swift and often deadly, but luckily the disease is not very communicable. Meningitis is an inflammation of the tissues surrounding the brain and spinal cord. Bacterial meningitis is a deadly form of this disease that is fairly uncommon but extremely serious, especially to young children. Every year about 5 out of 100,000 children under the age of 2 will contract bacterial meningitis in the United States. Bacterial meningitis can be caused by a few different species of bacteria such as Haemophilus influenza and Neiserria meningitidis. Viral meningitis, unlike bacterial meningitis, is much more common but less fatal.
While cases of bacterial meningitis are most common in children, they can affect adults as well. The key to beating this disease, once it is contracted, is through early detection. The primary symptoms include a fever greater than 101¼ F and a sudden severe headache. These two symptoms may also be accompanied by rashes, confusion, agitation, sleepiness, vomiting, or even a coma. If you notice any combination of these symptoms, it is imperative to get to the doctor as soon as possible. If detected early enough, bacterial meningitis can be treated with antibiotics. A vaccine for bacterial meningitis does exist; however, it is not effective against all strains of the disease-causing bacteria.
I have spent my summer conducting research in Dr. Igor Stojiljkovic’s lab at Emory University. My research revolves around some interesting mutations in Neisseria meningitidis. The only host for this bacteria is humans, and in order to survive in the human body it must have an iron source. Two different cell receptors on the bacteria can extract iron from human hemoglobin. These cell receptors can also express an "on" or an "off" phase. In the "on" stage the receptors can accept hemoglobin, and in the "off" stage they cannot. This switching between the "on" and "off" phases is known as phase variation. Phase variation in Neisseria meningitidis is caused by an addition or deletion mutation in repeated sequences of the DNA. For instance, an "on" sequence for one cell receptor may contain 9 guanines (one of the four nucleic bases) before the gene while the "off" sequence may contain 8 or 10.
These addition/deletion mutations are usually fixed by proteins via a mechanism known as mismatch repair. Mismatch repair is one method of correcting mutations in a number of organisms, including humans. There are about 6 different genes responsible for conducting mismatch repair in Neisseria meningitidis. One gene, mutL, is also found in human mismatch repair systems. Interestingly enough, a mutation in the mutL gene in humans can cause a form of kidney cancer. Why then would Neiserria meningitidis have such a high incidence of mutation in the genes coding for mismatch repair? In order to answer this question, we can think of the virulence of HIV. The HIV virus is so deadly and hard to combat because of its hypermutability; therefore it makes sense that some bacteria would also evolve hypermutations in order to live successfully within their hosts. Hypermutations, however, are also what cause cancers in animals; however, the pathogenetic benefits of hypermutation in mismatch repair for Neiserria meninigitidis easily outweigh any possible risks. Researchers hypothesize that the frequency of phase variation of hemoglobin receptors in Neiserria meningitidis is related to the virulence of the particular strains. In other words, those strains that are most deadly tend to have higher frequencies of phase variation; that is, they tend to switch between the "on" and "off" phases more often.
We are currently studying the effects of "knocking out" the genes responsible for mismatch repair. As a result, we hypothesize that the frequency of phase variation should increase because mismatch repair will not be as effective at correcting the mistakes in the gene. For instance, if we "knock out" the mutL gene, we expect to see a higher rate of phase variation. This is because the mismatch repair system has been adversely affected by the "knock out" and cannot fix the addition/deletions as well. Hopefully many years down the road, through the continued efforts of such research, this disease will be a problem of the past.
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