Normal Bacterial Flora of Humans (page 5)

(This chapter has 5 pages) Kenneth Todar, PhD Dental Caries, Gingivitis and Periodontal Disease The most frequent and economically-important condition in humans resulting from interactions with our normal flora is probably dental caries. Dental plaque, dental caries, gingivitis and periodontal disease result from actions initiated and carried out by the normal bacterial flora. Dental plaque, which is material adhering to the teeth, consists of bacterial cells (60-70% the volume of the plaque), salivary polymers, and bacterial extracellular products. Plaque is a naturally-constructed biofilm, in which the consortia of bacteria may reach a thickness of 300-500 cells on the surfaces of the teeth. These accumulations subject the teeth and gingival tissues to high concentrations of bacterial metabolites, which result in dental disease. The dominant bacterial species in dental plaque are Streptococcus sanguis andStreptococcus mutans, both of which are considered responsible for plaque.

Streptococcus mutans. Gram stain. CDC.

Plaque formation is initiated by a weak attachment of the streptococcal cells to salivary glycoproteins forming a pellicle on the surface of the teeth. This is followed by a stronger attachment by means of extracellular sticky polymers of glucose (glucans) which are synthesized by the bacteria from dietary sugars (principally sucrose). An enzyme on the cell surface of Streptococcus mutans, glycosyl transferase, is involved in initial attachment of the bacterial cells to the tooth surface and in the conversion of sucrose to dextran polymers (glucans) which form plaque.

Dental plaque, scanning electron micrograph illustrating the diversity of microbes in plaque.

Dental Caries is the destruction of the enamel, dentin or cementum of teeth due to bacterial activities. Caries are initiated by direct demineralization of the enamel of teeth due to lactic acid and other organic acids which accumulate in dental plaque. Lactic acid bacteria in the plaque produce lactic acid from the fermentation of sugars and other carbohydrates in the diet of the host.Streptococcus mutans and Streptococcus sanguis are most consistently been associated with the initiation of dental caries, but other lactic acid bacteria are probably involved as well. These organisms normally colonize the occlusal fissures and contact points between the teeth, and this correlates with the incidence of decay on these surfaces.

Cross section of a tooth illustrating the various structural regions susceptible to colonization or attack by microbes.

Streptococcus mutans in particular has a number of physiological and biochemical properties which implicate it in the initiation of dental caries. 1. It is a regular component of the normal oral flora of humans which occurs in relatively large numbers. It readily colonizes tooth surfaces: salivary components (mucins, which are glycoproteins) form a thin film on the tooth called the enamel pellicle. The adsorbed mucins are thought to serve as molecular receptors for ligands on the bacterial cell surface. 2. It contains a cell-bound protein, glycosyl transferase, that serves an adhesin for attachment to the tooth, and as an enzyme that polymerizes dietary sugars into glucans that leads to the formation of plaque. 3. It produces lactic acid from the utilization of dietary carbohydrate which demineralizes tooth enamel. S. mutans produces more lactic acid and is more acid-tolerant than most other streptococci. 4. It stores polysaccharides made from dietary sugars which can be utilized as reserve carbon and energy sources for production of lactic acid. The extracellular glucans formed by S. mutans are, in fact, bacterial capsular polysaccharides that function as carbohydrate reserves. The organisms can also form intracellular polysaccharides from sugars which are stored in cells and then metabolized to lactic acid. Streptococcus mutans appears to be important in the initiation of dental caries because its activities lead to colonization of the tooth surfaces, plaque formation, and localized demineralization of tooth enamel. It is not however, the only cause of dental decay. After initial weakening of the enamel, various oral bacteria gain access to interior regions of the tooth. Lactobacilli, Actinomyces, and various proteolytic bacteria are commonly found in human carious dentin and cementum, which suggests that they are secondary invaders that contribute to the progression of the lesions.

Actinomyces israelii

Periodontal Diseases are bacterial infections that affect the supporting structures of the teeth (gingiva, cementum, periodontal membrane and alveolar bone). The most common form, gingivitis, is an inflammatory condition of the gums. It is associated with accumulations of bacterial plaque in the area. Increased populations of Actinomyces have been found, and they have been suggested as the cause.

Diseases that are confined to the gum usually do not lead to loss of teeth, but there are other more serious forms of periodontal disease that affect periodontal membrane and alveolar bone resulting in tooth loss. Bacteria in these lesions are very complex populations consisting of Gram-positive organisms (includingActinomyces and streptococci) and Gram-negative organisms (including spirochetes and Bacteroides). The mechanisms of tissue destruction in periodontal disease are not clearly defined but hydrolytic enzymes, endotoxins, and other toxic bacterial metabolites seem to be involved. END OF CHAPTER Previous Page Return to Page 1

Viruses that most commonly attack the human respiratory tract are influenza virus, parainfluenza viruses, respiratory syncytial virus (RSV), adenoviruses, measles virus, rhinoviruses, and coronaviruses (64). The main bacterial pathogens found in this tract areStreptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus, Neisseria meningitidis, Mycobacterium tuberculosis, Bordetella pertussis, and, in immunocompromised patients, Pseudomonas aeruginosa (37). This chapter describes how some of these viruses and bacteria can cooperate to cause respiratory diseases which are more severe than those caused by either pathogen alone. Clinical, pathological, and epidemiological observations on natural disease, which suggest that such cooperation occurs, are examined first. This is followed by experiments using either animal models or, occasionally, human infections which prove the case. Finally, possible mechanisms to explain the increased severity of disease arising from dual infections are explaine

Several other diseases, below, are acquired by inhaling particles from environmental sources, not directly from an infected person. Disease
Psittacosis (Chlamydia psittaci) Legionnaire's disease (Legionella pneumophila) Acute allergic alveolitis (various fungal and actinomycete spores) Aspergillosis (Aspergillus fumigatus, A. flavus, A. niger) Histoplasmosis (Histoplasma capsulatum) Coccidioidomycosis (Coccidioides immitis)

Source
Dried, powdery droppings from infected birds (parrots, pigeons, etc.) Droplets from air-conditioning systems, water storage tanks, etc., where the bacterium grows. Fungal or actinomycete spores from decomposing organic matter (composts, grain stores, hay, etc.) Fungal spores inhaled from decomposing organic matter Spores of the fungus, in old, weathered bat or bird droppings Spores in air-blown dust in desert regions (Central, South and North

America) where the fungus grows in the soil ______________________________________________________________________ ____________________ Psittacosis is a serious disease acquired by handling birds or by inhaling dust from bird faeces. It is caused by the bacterium Chlamydia psittaci, an obligate intracellular parasite. After entering the respiratory tract, the cells are transported to the liver and spleen, multiply there and then invade the lungs, causing inflammation, haemorrhage and pneumonia. Legionnaire's disease is a fairly common form of pneumonia in older or immunocompromised people. It is seldom transmitted directly from person to person. The bacterium is an aquatic rod-shaped species with a temperature optimum of about 36oC, and is a common inhabitant of warm-water systems in buildings. Infection occurs when people inhale aerosol droplets containing the bacteria. Extrinsic allergic alveolitis is a serious hypersensitive response, usually associated with repeated exposure to airborne spores in the work environment. A classic example is the condition termed farmer's lung, caused by exposure to spores of thermophilic actinomycetes. Aspergillosis, Histoplasmosis and Coccidioidomycosis are examples of serious fungal infections of humans, initiated by spores deposited in the alveoli. They can be life-threatening diseases of immunocompromised people, when the fungi disseminate from the lungs to major organs of the body. However, in all cases the infection of humans is incidental to the fungus, playing no part in its normal biology. These are fungi that grow naturally as decomposer organisms in soil, bird faeces or other organic substrates.

Bacterial Diarrheas
Enterotoxin-Mediated Diarrheas: Enterotoxigenic bacteria, such as Vibrio cholerae and enterotoxigenic Escherichia coli strains, colonize the upper bowel and cause watery diarrhea by producing an enterotoxin that stimulates mucosal cells to secrete fluid via an increase in intracellular AMP. Invasive Diarrheas: Invasive bacteria, such as Shigella and Campylobacter, penetrate the intestinal mucosa. A bloody, mucoid diarrheal stool with inflammatory exudate is produced.

Viral Diarrheas
Rotavirus and Calicivirus (formerly Norwalk virus) are major causes of diarrheal disease. Rotavirus diarrhea affects mostly young children; Calicivirus causes disease in all age groups

Parasitic Diarrheas

Some protozoa (especially Entamoeba histolytica and Giardia lamblia) as well as some intestinal helminths can cause diarrheal disease.

iseases Caused by Overgrowth of Potential Pathogens

The normal intestinal flora includes small populations of organisms that cause disease if they overgrow. For example, overgrowth ofClostridium difficile produces severe inflammation of the colon with diarrhea (pseudomembranous colitis). Administration of antibiotics initiates the process by suppressing the normal flora.

Peritonitis
Bacteria from the intestinal flora are the prime cause of infection in the peritoneal cavity when the normal barriers of the intestinal wall are violated. The intestinal wall can be perforated by trauma (knife wounds, gunshot wounds, blunt trauma), by disease (appendicitis, penetrating intestinal cancers), or by surgical procedures. Once the mucosal barrier is breached, bacteria penetrate through the intestinal wall into the normally sterile peritoneal cavity and its surrounding structures. Poor circulation, reduced oxygen supply, and dead tissue in the vicinity of the perforation promote the formation of an abscess and particularly favor the growth of anaerobic bacteria. Cultures of a peritoneal abscess generally yield several types of bacteria from the intestinal microflora, particularly species of Bacteroides, Clostridium, and Peptostreptococcus and E coli.

Bacterial Diarrheas
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Enterotoxin-Mediated Diarrheal Diseases

Several enterotoxin-producing bacteria cause diarrheal diseases (Table 95-1). The diarrheal disease caused by Vibrio cholerae and enterotoxigenic strains of E coli has three main characteristics. First, there is intestinal fluid loss that is related to the action of an enterotoxin on the small bowel epithelial cells. Second, the organism itself does not invade the mucosal surface; rather, it colonizes the upper small bowel, adhering to the epithelial cells and elaborating the enterotoxin. The mucosal architecture remains intact with no evidence of cellular destruction. Bacteremia does not occur. Third, the fecal effluent is watery and often voluminous, so that the diarrhea can result in clinical dehydration. The fluid originates in the upper small bowel. where the enterotoxin is most active.

Table 95-1 Toxin-Producing Bacteria Associated With Diarrheal Disease.

Cholera
The paradigm of the enterotoxigenic diarrheal diseases is cholera (see Ch. 24), in which stool volume can exceed 1 L/h, with daily fecal outputs of 15 to 20 L if the patient is kept hydrated. Cholera is caused by V cholerae, which is usually ingested in contaminated water. Vibrios that survive passage through the stomach colonize the surface of the small intestine, proliferate, and elaborate the enterotoxin. Cholera toxin acts via adenylate cyclase to stimulate secretion of water and electrolytes from the epithelial cells into the lumen of the gut. The duodenum and upper jejunum are more sensitive to the toxin than the ileum is. The colon is relatively insensitive to the toxin and may still absorb water and electrolytes normally. Thus, cholera is an overflow diarrhea, in which the large volumes of fluid produced in the upper intestine overwhelm the resorptive capacity of the lower bowel. Cholera stool is described as resembling rice watera clear fluid flecked with mucusand is isotonic with plasma. Microscopy reveals no inflammatory cells in the fecal effluent; all that can be seen are small numbers of shed mucosal cells.

Enterotoxigenic E coli Diarrhea

Certain strains of E coli cause diarrheal disease by elaborating enterotoxins (see Ch. 25). These strains produce two types of enterotoxin. One, called heat-labile toxin, is similar in structure and in its mechanism of action to cholera toxin. The other, called heat-stable toxin, appears to act via guanylate cyclase. Enterotoxigenic E coli strains are the most common cause of travelers' diarrhea

Other Diarrhea-Causing Toxins

Many strains of Shigella produce an enterotoxin, called Shiga toxin, that causes secretion of fluid from the small intestine (see Ch. 22). Shiga toxin has a destructive, cytotoxic effect on the small-bowel epithelium, causing gross injury to the bowel surface. It does not activate adenylate cyclase. E coli 0157:H7, the organism associated with consumption of undercooked chopped meat, also produces a Shiga-like toxin; it causes bloody diarrhea and colitis. An organism that produces a different type of cytotoxin is Vibrio parahaemolyticus, a bacterium associated with seafood. Food-poisoning strains of Staphylococcus aureus and Clostridium perfringens both produce enterotoxins that are cytotoxic. The staphylococcal enterotoxin also has a direct effect on the vomiting center in the brain.

Gastrointestinal Disease Caused by Invasive Bacteria

Unlike the enterotoxigenic organisms, invasive bacteria exert their main impact on the host by causing gross destruction of the epithelial architecture; histologic findings include mucosal ulceration and an inflammatory reaction in the lamina propria. The principal pathogens in this group are Salmonella, Shigella, Campylobacter, invasive E coli, and Yersinia. The enteric viruses also invade intestinal epithelial cells, but the extent of mucosal destruction is considerably less than that caused by invasive bacterial pathogens.

Salmonella Enteritis
Salmonella species are a common cause of food poisoning. The main site of attack is the lower ileum, where the salmonellae cause mucosal ulceration. They rapidly make their way through the epithelial surface into the lamina propria and enter the lymphatics and bloodstream. At least two virulence factors are associated with intestinal infection: one responsible for mucosal invasion, and the other causing secretion of fluid and electrolytes into the bowel.

Shigella Dysentery
Shigella organisms cause bacillary dysentery, an invasive diarrheal disease of the lower bowel in which the stool contains an inflammatory exudate composed of polymorphonuclear leukocytes. The bacilli invade the epithelium of the colon and cause superficial ulceration. This invasive process depends on the presence of two virulence factors. The first mediates the initial penetration of the mucosal surface by destroying the brush border; the bacteria are subsequently engulfed by invagination of the plasma membrane. The second virulence factor allows the organism to multiply within the mucosal tissue. Mucosal ulceration results, accompanied by an intense inflammatory response in the lamina propria. The infection is usually restricted to the mucosa; lymph node involvement and bacteremia are uncommon.

Fluid Production in Invasive Diarrheal Diseases

The mechanism(s) by which the fluid that causes watery diarrhea is produced in the invasive diarrheal diseases is under debate. Three mechanisms have been proposed. First, Shigella and possibly Salmonella strains apparently produce an enterotoxin that stimulates the mucosa to secrete water and electrolytes. Second, there is evidence that invasive organisms stimulate prostaglandin synthesis at the site of inflammation and that the prostaglandins induce fluid secretion. In experimental animals, fluid secretion can be blocked by prostaglandin inhibitors such as indomethacin and aspirin. Third, some evidence suggests that damage to the colonic epithelium causes diarrhea by prevention of normal resorption of fluid.

Viral Diarrheas
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Two virusesrotavirus (see Ch. 63) and Calicivirus (Norwalk virus) (see Ch. 65)have been identified as major enteric pathogens in humans. The rotaviruses are a very important cause of infantile diarrhea, which in undeveloped countries can be fatal. Adults may be infected and shed virus, but clinical disease appears almost exclusively in children younger than 2 years. Calicivirus, in contrast, can produce gastroenteritis in all age groups and is a cause of major epidemics. The initial lesion forms in the proximal small bowel. The mucosal architecture is damaged, with shortening of the villi and hyperplasia of the crypts. An inflammatory exudate then appears in the lamina propria. The mechanisms responsible for fluid secretion in viral diarrheas have not been elucidated. It is known that infection with Calicivirus can produce steatorrhea and xylose malabsorption and causes direct damage to brush border enzymes. The activity of adenylate cyclase in the epithelial cells is not altered in the acute illness.

Parasitic Diarrheas
Go to: Several species of protozoa and helminths can cause diarrheal disease. Some of these infections can be acquired in the United States, although exposure to enteric parasites is far more common in tropical and developing countries. Some of the more common causes of parasitic diarrhea are Entamoeba histolytica, Giardia lamblia, Strongyloides stercoralis, and the intestinal flukes.

Clinical Diagnosis of Diarrheal Disease

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