Microbiology, Lec 25.
Our goal today is to discuss dental caries and ulcers. I will also save some time at the end of class to review and answer questions about the exam - which is THIS THURSDAY, April 27th!!!!!
Well actually, after having written most of the test for thurs., I want to get your minds back on Bacteria and fill in a few things we never got back to. We've been talking about viruses that are obligate pathogens, now let's look at some very obligate pathogens that are Bacteria (ie. Chlamydia and Rickettsia.)
Chlamydia (read page 449 - 450)
Members of the genus Chlamydia are intracellular (obligate) parasites that cannot produce their own ATP. Sequencing data show that they are Gram negative Bacteria related to the Planctomycetes (lec. 6). They are very small rods (200 x 400 nm) that also have a very reduced genome compared to other bacteria (genome size of about 1000 kilobases; compare to HIV E. coli, and Streptomyces genome sizes of 9, 4600 and 8000 kilobases, respectively).
They also have a complex life cycle (see Fig. 21.13). Three known species all are pathogens of humans and/or other animals e.g.
C. trachomatis causes trachoma (an eye disease) and one of the most common venereal diseases of humans (see pgs. 800-802).
Rickettsia (read pages 803-805)
Several members of the genus Rickettsia cause human diseases (e.g. Typhus and Rocky Mountain Spotted Fever). Sequencing data indicate that their closest relatives are the genus Ehrlichiaand mitochondria from Eucaryotic organisms (see Figure 2 in Molecular Microbiology vol. 15(1), pg. 5). Phylogenetically, they belong in the alpha Proteobacteria (lec. 6).
We discussed the normal microbiota of the human mouth in lec. 19. Of special concern for dental caries are organisms that adhere to the teeth and form plaque. Dental plaque is just many layers of bacteria and their surrounding polysaccharide matrix (capsules, lec. 3). Plaque is something that is constantly forming. Figure 19.4 (Brock) shows bacterial microcolonies growing on pieces of tooth-like material inserted into the mouth for 6 hours. Figure 19.5 shows the really gross build-up of plaque on teeth that haven't been brushed for ten days. Figure 19.6 shows a 50 micrometer-thick layer of plaque that consists mostly of cells of Streptococcus mutans and S. sobrinus..The bacteria of dental plaque.
Initial colonists of the tooth surface are mostly streptococci (lec. 7). Once these build up, a series of other bacteria attach in a receptor mediated way (via lectins and carbohydrate surface receptors) to the streptococci (see Fig. 38.4 a nd b). The second wave includes anaerobic filamentous bacteria, such as Fusobacteriumspecies (Gm -, obligate anaerobes that produce various acids, many are "fusiform", fus = L. for spindle, Draw elongated spindles) and finally spirochaetes (e.g. Borrelia & Treponema spp.) and anaerobic species of Actinomyces(lec. 7).
The thicker the plaque gets the more anaerobic it can become (why?).
Dental caries.
Most research on dental caries has focused on S. mutans and S. sobrinus. In terms of tooth geography, S. mutans dominates in the tight spaces between teeth and crevasses in teeth, whereas S sobrinus is a better colonist of the smoother surfaces of teeth.The presence of sucrose in the human diet has been linked directly and indirectly to the prevalence of dental caries.
S. mutans has an enzyme (glucosyltransferase or dextransucrase; see Fig. 38.4c) that converts the disaccharide sucrose (table sugar) into a glucan polysaccharide, dextran (glucose molecules linked by alpha 1-6 bonds):
n Sucrose -------> dextran + n fructose
Dextran is very sticky and is part of the capsule of S. mutanswhen it eats sucrose. Remember from lec. 7 that S. mutansis homofermentative and therefore can convert one glucose (or fructose) to two molecules of lactic acid. Thus cavities are caused by lactic acid being trapped under the plaque where it dissolves the calcified tooth enamel.
Incorporation of fluoride into the calcium phosphate crystal matrix of teeth makes the matrix more resistant to decalcification by lactic acid.
Other evidence for how dental caries are caused comes from studies with germ-free (gnotobiotic) animals (lec. 19). Such animals will not get cavities unless they are fed sucrose and are inoculated with S. mutans. Neither S. mutans nor sucrose can cause cavities alone.
People in certain parts of Tanzania also do not get dental caries and they do not use sucrose in their diets. S. mutans is missing from the plaque of Tanzanian children, whereas almost all European and American children have S. mutansin their dental plaque.
There are approximately 20 million Americans with ulcers. Until recently, doctors attributed ulcers to stress and other non-microbial causes, but we now know that from 70 to 90% of all ulcers are caused by Helicobacterium pylori,a Gram -, microaerophilic, spiral-shaped bacterium (Epsilon-Proteobacteria; see Fig. 19.13). The genus Helicobacteriumcontains about 15 species all of which live in the stomachs or upper intestines of mammals. Only H. pylorihas been shown to be a pathogen.
The closest relative of Helicobacteriumis the genus Campylobacterwhich also contains pathogens (e.g. C. jejunicauses abortions in sheep and diarrhea in humans) and non-pathogens.see Fig. 37.14
Proof that H. pyloricauses ulcers has been mounting in recent years. The initial studies in the 1980s by several Australian microbiologists showed that H. pylori was found in the stomach biopsies of over 90% of their patients with ulcers (see KochÕs postulates; lec. 2). Their attempts to culture this organism were unsuccessful until they forgot about a bunch of plates and let them incubate for a long period of time under low-oxygen conditions.Finally, in 1993, a study was published in the New England J. of Med.which showed that 48 of 52 patients treated with antibiotics were cured of ulcers whereas none of the 52 patients receiving placebos were cured.