1. Medical Bacteriology MBIO 460 Lecture 5
Dr. Turki Dawoud
2nd Semester
1436/1437 H

2. Chapter Two Microbial Interactions with Humans
Beneficial Microbial Interactions with Humans.
Harmful Microbial Interactions with Humans.
Virulence Factors and Toxins.
Host Factors in Infection.

3. BENEFICIAL MICROBIAL INTERACTIONS
Overview of Human–Microbial Interactions
Through normal everyday activities, the human body is exposed to numerous microorganisms in the environment.
In addition, hundreds of species and manyindividual microbial cells, collectively referred to as the normal microbial flora, grow on or in the human body.
Most, but not all, microorganisms are not harmful in effect; as only some contribute directly to our health, and even fewer cause direct threats to health.

4. Colonization by Microorganisms
Mammals in utero develop in a sterile environment and have no exposure to microorganisms.
Starting with the birth process, colonization, growth of a microorganism after it has gained access to host tissues, begins as animals are exposed to microorganisms
The skin surfaces are readily colonized by many species.
Likewise, the oral cavity and gastrointestinal tract acquire microorganisms through feeding and exposure to the mother's body, which, along with other environmental sources, initiates colonization of the skin, oral cavity, upper respiratory tract, and gastrointestinal tract.

5. Different populations of microorganisms colonize individuals in different region and at different times.
For example, Escherichia coli, a normal inhabitant of the human and animal gut, colonizes the guts of infants in developing countries within several days after birth.
Infants in developed countries, however, typically do not acquire E. coli for several months; the first microorganisms to colonize the gut of these infants would more typically be Staphylococcus aureus and other microorganisms associated with the skin.
Genetic factors also play a role. Thus, the normal microbial flora is highly dependent on the conditions to which an individual is exposed.
The normal flora is highly diverse in each individual and may differ significantly between individuals, even in a given population.

6. Pathogens
A host is an organism that harbors a parasite, another organism that lives on or in the host and causes damage.
Microbial parasites are called pathogens.
The outcome of a host–parasite relationship depends on pathogenicity, the ability of a parasite to inflict damage on the host.
Pathogenicity differs considerably among potential pathogens, as does the resistance or susceptibility of the host to the pathogen.
An opportunistic pathogen causes disease only in the absence of normal host resistance.
“Pathogenicity” is basically the ability to cause disease; and the degree of pathogenicity is termed “Virulence”.

7. Virulence can be expressed quantitatively as the cell number that elicits disease in a host within a given time period.
Neither the virulence of the pathogen nor the relative resistance of the host is a constant factor.
The host–parasite interaction is a dynamic relationship between the two organisms, influenced by changing conditions in the pathogen, the host, and the environment.

8. Infection and Disease
Infection refers to any situation in which a microorganism is established and growing in a host, whether or not the host is harmed.
Disease is damage or injury to the host that impairs host function.
Infection is not the same with disease because growth of a microorganism on a host does not always cause host damage.
Thus, species of the normal microbial flora have infected the host, but seldom cause disease.
However, the normal flora sometimes cause disease if host resistance is compromised, as happens in diseases such as cancer and acquired immune deficiency syndrome (AIDS).

9. Host–Parasite Interactions
Animal hosts provide favorable environments for the growth of many microorganisms.
They are rich in the organic nutrients and growth factors required by chemo-organotrophs, and provide conditions of controlled pH, osmotic pressure, and temperature.
However, the animal body is not a consistent environment.
Each region or organ differs chemically and physically from others and thus provides a selective environment where the growth of certain microorganisms is favored.
For example, the skin, respiratory tract, and gastrointestinal tract provide selective chemical and physical environments that support the growth of a highly diverse micro-flora.

10. The relatively dry environment of the skin favors the growth of organisms that resist dehydration, such as the gram-positive bacterium Staphylococcus aureus.
The highly oxygenated environment of the lungs favors the growth of the obligatory aerobic Mycobacterium tuberculosis.
The anoxic environment of the large intestine supports growth of obligatory anaerobic bacteria such as Clostridium and Bacteroides.
Animals also possess defense mechanisms that collectively prevent or inhibit microbial invasion and growth.
The microorganisms that successfully colonize the host have avoid these defense mechanisms.

11. The Infection Process
Infections frequently begin at sites in the animal's mucous membranes. Mucous membranes consist of single or multiple layers of epithelial cells, tightly packed cells that interface with the external environment.
They are found throughout the body, lining the urogenital, respiratory, and gastrointestinal tracts.
Mucous membranes are frequently coated with a protective layer of viscous soluble glyco-proteins called mucus.
Microorganisms that contact host tissues at mucous membranes may associate loosely with the mucosal surface and are usually swept away by physical processes.
Microorganisms may also adhere more strongly to the epithelial surface as a result of specific cell–cell recognition between pathogen and host. Tissue infection may follow, breaching the mucosal barrier and allowing the microorganism to invade deeper into sub-mucosal tissues (Figure 28.1).

12. Bacterial interactions with mucous membranes. (a) Loose association
Bacterial interactions with mucous membranes.  (a) Loose association. (b) Adhesion. (c) Invasion into submucosal epithelial cells.

13. Microorganisms are almost always found on surfaces of the body exposed to the environment, such as the skin, and even on the mucosal surfaces of the oral cavity, respiratory tract, intestinal tract, and urogenital tract.
They are not normally found on or in the internal organs or in the blood, lymph, or nervous systems of the body.
The growth of microorganisms in these normally sterile environments indicates serious infectious disease.

14. 2.2 Normal Microbial Flora of the Skin
An average adult human has about 2 m2 of skin surface that varies greatly in chemical composition and moisture content.
The skin surface (epidermis) is not a favorable place for abundant microbial growth, as it is subject to periodic drying.
Most skin microorganisms are associated directly or indirectly with the apocrine (sweat) glands.
These are secretory glands found mainly in the underarms, genital regions, the nipples, and the umbilicus.
Inactive in childhood, they become fully functional at teens.
Figure 28.2 The human skin.  Microorganisms are associated primarily with the sweat ducts and the hair follicles.

15. Microbial populations thrive on the surface of the skin in these warm, humid places in contrast to the poor growth observed on smooth, dry skin surfaces.
Similarly, each hair follicle is associated with a sebaceous gland, a gland that secretes a lubricant fluid.
Hair follicles provide an attractive habitat for microorganisms in the area just below the surface of the skin.
The secretions of the skin glands are rich in microbial nutrients such as urea, amino acids, salts, lactic acid, and lipids.
The pH of human secretions is almost always acidic, the usual range being between pH 4 and 6.

16. The Skin Microflora
The normal flora of the skin consist of either resident or transient populations of bacteria and fungi, mainly yeasts.
Certain genera are highly conserved in healthy individuals, while others change over time.
In all, over 180 species of Bacteria and several species of fungi are found on the skin when samples from many individuals are gathered.
Samplings of individuals done several months apart indicate that certain members of the normal flora are extremely stable.
The most common and stable resident microorganisms are gram-positive Bacteria, generally restricted to a few genera, including species of Streptococcus and Staphylococcus; various species of Corynebacterium; and Propionibacterium, including Propionibacterium acnes, which contributes to a skin condition called acne.

17. These four genera account for over one-half of all species found.
The remaining groups of bacteria found on skin are much more transient, with over 70% changing with time and conditions on the individuals sampled.
Gram-negative Bacteria are occasional constituents of the normal skin flora because such intestinal organisms as Escherichia coli are continually being inoculated onto the surface of the skin by fecal contamination.
These gram-negative Bacteria seldom grow on skin due to their inability to compete with gram-positive organisms that are better adapted to the dry conditions. The gram-negative rod Acinetobacter, however, is an exception and commonly colonizes skin.

18. Malassezia spp. are the most common fungi found on skin.
At least five species of this yeast are typically found in healthy individuals.
The lipophilic yeast Pityrosporum ovalis is occasionally found on the scalp.
In the absence of host resistance, as in patients with AIDS or in the absence of normal bacterial flora, other yeasts such as Candida and other fungi sometimes grow and cause serious skin infections

19. Although the resident microflora remains more or less constant, various environmental and host factors may influence its composition.
The weather may cause an increase in skin temperature and moisture, which increases the density of the skin microflora.
The age of the host has an effect; young children have a more varied microflora and carry more potentially pathogenic gram-negative Bacteria than do adults.
Personal hygiene influences the resident microflora; individuals with poor hygiene usually have higher microbial population densities on their skin. Organisms that cannot survive on the skin generally succumb from either the skin's low moisture content or low pH (due to organic acid content).

20. QUESTIONS??

21. Medical Bacteriology MBIO 460 Lecture 6
Dr. Turki Dawoud
2nd Semester
1436/1437 H

22. Normal Microbial Flora of the Oral Cavity
The oral cavity is a complex, heterogeneous microbial habitat.
Saliva contains microbial nutrients, but it is not an especially good growth medium because the nutrients are present in low concentration and saliva contains antibacterial substances.
For example, saliva contains lysozyme, an enzyme that cleaves glycosidic linkages in peptidoglycan present in the bacterial cell wall, weakening the wall and causing cell lysis .
Lacto-peroxidase, an enzyme in both milk and saliva, kills bacteria by a reaction in which singlet oxygen is generated
Despite the activity of these antibacterial substances, food particles and cell debris provide high concentrations of nutrients near surfaces such as teeth and gums, creating favorable conditions for extensive local microbial growth, tissue damage, and disease.

23. The Tooth and Dental Plaque
The tooth consists of a mineral matrix of calcium phosphate crystals (enamel) surrounding living tooth tissue (dentin and pulp) (Figure 28.3).
Bacteria found in the mouth during the first year of life (when teeth are absent) are predominantly aerotolerant anaerobes such as streptococci and lactobacilli.
However, other bacteria, including some aerobes, occur in small numbers.
When the teeth appear, the balance of the microflora shift toward anaerobes that are specifically adapted to growth on surfaces of the teeth and in the gingival crevices.
Figure 28.3  Section through a tooth.  The diagram shows the tooth architecture and the surrounding tissues that anchor the tooth in the gum.

24. Bacterial colonization of tooth surfaces begins with the attachment of single bacterial cells.
Even on a freshly cleaned tooth surface, acidic glycoproteins from the saliva form a thin organic film several micrometers thick. This film provides an attachment site for bacterial micro-colonies (Figure 28.4).
Streptococci (primarily Streptococcus sanguis, S. sobrinus, S. mutans, and S. mitis) can then colonize the glycoprotein film. Extensive growth of these organisms results in a thick bacterial layer called dental plaque.
Figure 28.4  Microcolonies of bacteria.  (a) The colonies are growing on a model tooth surface inserted into the mouth for 6 h. (b) Higher magnification of the preparation in (a). Note the diverse morphology of the organisms present and the slime layer (arrows) holding the organisms together.
Figure 28.6  Electron micrographs of thin sections of dental plaque
Figure 28.5  Distribution of dental plaque

25. If plaque continues to form, filamentous anaerobes such as Fusobacterium species begin to grow.
The filamentous bacteria embed in the matrix formed by the streptococci and extend perpendicular to the tooth surface, making an ever-thicker bacterial layer.
Associated with the filamentous bacteria are spirochetes such as Borrelia species, gram-positive rods, and gram-negative cocci.
In heavy plaque, filamentous obligatory anaerobic organisms such as Actinomyces may predominate.
Thus, dental plaque can be considered a mixed-culture biofilm, consisting of a relatively thick layer of bacteria from several different genera as well as accumulated bacterial products.

26. The anaerobic nature of the oral flora may seem surprising considering the intake of oxygen through the mouth.
However, anoxia develops due to the metabolic activities of facultative bacteria growing on organic materials at the tooth surface.
The plaque buildup produces a dense matrix that decreases oxygen diffusion to the tooth surface, forming an anoxic microenvironment.
The microbial populations within dental plaque exist in a microenvironment of their own making and maintain themselves in the face of wide variations in the conditions in the macro-environment of the oral cavity.

27. Dental Caries
As dental plaque accumulates, the resident microflora produce locally high concentrations of organic acids that cause decalcification of the tooth enamel (Figure 28.3), resulting in dental caries (tooth decay).
Thus, dental caries is an infectious disease. The smooth surfaces of the teeth are relatively easy to clean and resist decay.
The tooth surfaces in and near the gingival crevice, however, can retain food particles and are the sites where dental caries typically begins. 
Figure 28.3  Section through a tooth.  The diagram shows the tooth architecture and the surrounding tissues that anchor the tooth in the gum.
Diets high in sucrose (table sugar) promote dental caries.
Lactic acid bacteria ferment sugars to lactic acid. The lactic acid dissolves some of the calcium phosphate in localized areas, and proteolysis of the supporting matrix occurs through the action of bacterial proteolytic enzymes.

28. Bacterial cells slowly penetrate further into the decomposing matrix.
The structure of the calcified tooth tissue also plays a role in the extent of dental caries. For example, incorporation of fluoride into the calcium phosphate crystal tooth matrix increases resistance to acid decalcification.
Consequently, fluorides in drinking water and dentifrices inhibit tooth decay.
Two bacteria implicated in dental caries are Streptococcus sobrinus and Streptococcus mutans, both lactic acid bacteria. S. sobrinus is probably the primary organism causing decay of smooth surfaces because of its specific affinity for salivary glycoproteins found on smooth tooth surfaces (Figure 28.6). 
S. mutans, found predominantly in crevices and small fissures, produces dextran, a strongly adhesive polysaccharide that it uses to attach to tooth surfaces (Figure 28.7). S. mutans produces dextran only when sucrose is present by activity of the enzyme dextransucrase:
Figure 28.7  Scanning electron micrograph of the cariogenic bacterium  Streptococcus mutans. The sticky dextran material holds the cells together as filaments. Individual cells are about 1 µm in diameter.

29. Dextransucrase
N -Sucrose
dextran (glucose)+ n Fructose
Susceptibility to tooth decay varies and is affected by genetic traits in the individual as well as by diet and other extraneous factors.
For example, sucrose, highly cariogenic because it is a substrate for dextransucrase, is part of the diet of most individuals in developed countries.
Studies of the distribution of the cariogenic oral streptococci show a direct correlation between the presence of S. mutans and S. sobrinus and the extent of dental caries.
In the United States and Western Europe, 80–90% of all individuals are infected by S. mutans, and dental caries is nearly universal.
By contrast, S. mutans is absent from the plaque of Tanzanian children, and dental caries does not occur, presumably because sucrose is almost completely absent from their diets.

30. Microorganisms in the mouth can also cause other infections.
The areas along the periodontal membrane at or below the gingival crevice (periodontal pockets) (Figure 28.3) can be infected with microorganisms, causing inflammation of the gum tissues (gingivitis) leading to tissue and bone-destroying periodontal disease.
Some of the genera involved include fusi-form bacteria (long, thin, gram-negative rods with tapering ends) such as the facultative aerobe Capnocytophaga.
The aerobe Rothia, and even strictly anaerobic methanogens, such as Methanobrevibacter (Archaea), may also be present.
Figure 28.3  Section through a tooth.  The diagram shows the tooth architecture and the surrounding tissues that anchor the tooth in the gum.

31. QUESTIONS??