1. Medical Bacteriology MBIO 460 Lecture 9 Dr. Turki Dawoud 2 nd Semester 1436/1437 H

2. HARMFUL MICROBIAL INTERACTIONS WITH HUMANS - Microbial interactions may be harmful to the host and cause disease. - Here we examine mechanisms of pathogenesis, the ability of microorganisms to cause disease. - Microbial pathogenesis begins with exposure and adherence of the microorganisms to host cells, followed by invasion, colonization, and growth. Unrestricted growth of the pathogen then results in host damage. - Pathogens use several different strategies to establish virulence, the relative ability of a pathogen to cause disease (Figure 28.12). Here we consider the factors responsible for establishing virulence.

3. Figure 28.12 Microorganisms and mechanisms of pathogenesis. Following exposure to a pathogen, events in pathogenesis begin with specific adherence

4. Entry of the Pathogen into the Host A pathogen must usually gain access to host tissues and multiply before damage can be done. In most cases, this requires that the organisms penetrate the skin, mucous membranes, or intestinal epithelium, surfaces that are normally microbial barriers. Specific Adherence Most microbial infections begin at breaks or wounds in the skin or on the mucous membranes of the respiratory, digestive, or genitourinary tract. Bacteria or viruses able to initiate infection often adhere specifically to epithelial cells (Figure 28.13) through macromolecular interactions on the surfaces of the pathogen and the host cell Figure 28.13 Adherence of pathogens to animal tissues. (a) Transmission electron micrograph of a thin section of Vibrio choleraeadhering to the brush border of rabbit villi in the intestine. Note the absence of a capsule. (b) Enteropathogenic Escherichia coli in a fatal model of infection in the newborn calf. The bacterial cells are attached to the brush border of calf intestinal villi through their distinct capsule. The rods are about 0.5 µm in diameter.

5.  Most pathogens do not adhere to all epithelial cells equally, but selectively adhere to cells in a particular region of the body.  For example, Neisseria gonorrhoeae, the pathogen that causes the sexually transmitted disease gonorrhea, adheres more strongly to urogenital epithelia. N. gonorrhoeae has a surface protein called Opa (opacity associated protein) that binds specifically to a host protein called CD66 found only on the surface of human epithelial cells.  Thus N. gonorrhoeae interacts exclusively with host cells by binding a specific cell surface protein. The species of the host also influences specificity.  In many cases, a bacterial strain that normally infects humans adheres more strongly to the appropriate human cells than to similar cells in another animal (for example, the rat) and vice versa.

6. Some macromolecules responsible for bacterial adherence are not covalently attached to the bacteria. These are usually polysaccharides, proteins, or protein–carbohydrate mixtures synthesized and secreted by the bacteria (Section 4.9). A loose network of polymer fibers extending outward from a cell is called a slime layer (Figure 28.4b). A polymer coat consisting of a dense, well-defined layer surrounding the cell is called a capsule (Figures 28.13 and28.14). These structures may be important for adherence to other bacteria as well as to host tissues. In some cases, these structures can protect bacteria from host defense mechanisms such as phagocytosis (Section 29.2). Figure 28.14 Bacillus anthracis capsules. (a)Capsules of B. anthracis on bicarbonate agar media. Encapsulated colonies are typically very large and mucoid in appearance. The individual encapsulated colonies are 0.5 cm in diameter. (b)Direct immunofluorescent stain of B. anthraciscapsules. Antibodies coupled to fluorescein isothiocyanate (FITC) stain the capsule bright green, indicating that the capsule extends up to 1 µm from the cell, which is about 0.5 µm in diameter

7.  Fimbriae and pili (Section 4.9) are bacterial cell surface protein structures that may also function in the attachment process.  For instance, the pili of Neisseria gonorrhoeae play a key role in attachment to urogenital epithelium, and fimbriated strains of Escherichia coli (Figure28.15) are more frequent causes of urinary tract infections than strains lacking fimbriae.  Among the best-characterized fimbriae are the type I fimbriae of enteric bacteria (Escherichia, Klebsiella, Salmonella, and Shigella). Type I fimbriae are uniformly distributed on the surface of cells. Pili are typically longer than fimbriae, with fewer pili found on the cell surface.  Both pili and fimbriae function by binding host cell surface glycoproteins, initiating attachment. Flagella can also increase adherence to host cells (see Figure 28.17)

8. Some major factors important in microbial adherence are shown in Table 28.3.

9. Invasion - A few microorganisms are pathogenic solely because of the toxins they produce. These organisms do not need to gain access to host tissues, and we will discuss them separately. - However, most pathogens must penetrate the epithelium to initiate pathogenicity, a process called invasion. At the point of entry, usually at small breaks or lesions in the skin or in mucosal surfaces, growth is established. -Growth may also begin on intact mucosal surfaces, especially if the normal flora is altered or eliminated, for example, by antibiotic therapy. -- Pathogens may then more readily colonize the tissue and begin the invasion process. Pathogen growth may also be established at sites distant from the original point of entry. Access to distant, usually interior, sites is through the blood or lymphatic circulatory system.

10. QUESTIONS??