Microbial Virulence Factors And Pathogenesis Of Bacterial Infection PDF

Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ MICROBIAL VIRULENCE FACTORS AND PATHOGENESIS OF BACTERIAL INFECTION A microorganism is a pathogen if it is capable of causin...

Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ MICROBIAL VIRULENCE FACTORS AND PATHOGENESIS OF BACTERIAL INFECTION A microorganism is a pathogen if it is capable of causing disease; however, some organisms are highly pathogenic (i.e., they often cause disease), whereas others cause disease rarely. Opportunistic pathogens are those that rarely, if ever, cause disease in immunocompetent people but can cause serious infection in immunocompromised patients. These opportunists are frequent members of the body’s normal flora. The origin of the term opportunistic refers to the ability of the organism to take the opportunity by reduced host defenses to cause disease. Virulence is a quantitative measure of pathogenicity and is measured by the number of organisms required to cause disease. The 50% lethal dose (LD50) is the number of organisms needed to kill half the hosts, and the 50% infectious dose (ID50) is the number needed to cause infection in half the hosts. Organisms with a lower LD50 (or ID50) are said to be more virulent than those with a higher LD50 (or ID50) because fewer organisms are needed to cause death or disease. STAGES OF BACTERIAL PATHOGENESIS Most bacterial infections are acquired from an external source. However, some bacterial infections are caused by members of the normal flora and, as such, are not transmitted directly prior to the onset of infection. A generalized sequence of the stages of infection is as follows: (1) Transmission from an external source into the portal of entry. (2) Evasion of primary host defenses such as skin or stomach acid. (3) Adherence to mucous membranes, usually by bacterial pili. (4) Colonization by growth of the bacteria at the site of adherence. (5) Disease symptoms caused by toxin production or invasion accompanied by 1 Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ inflammation. (6) Host responses, both nonspecific and specific (immunity), during steps 3, 4, and 5. (7) Progression or resolution of the disease. DETERMINANTS OF BACTERIAL PATHOGENESIS 1. Transmission The modes of transmission of microbes include both human-to human and nonhuman-to-human processes. Nonhuman sources include animals, soil, water, and food. Human-to-human transmission can occur either by direct contact or indirectly via a vector such as an insect, notably ticks or mosquitoes. Animal-to-human transmission can also occur either by direct contact with the animal or indirectly via a vector. The main “portals of entry” into the body are the respiratory tract, gastrointestinal tract, skin, and genital tract. Human diseases for which animals are the reservoir are called zoonoses. 2. Adherence to Cell Surfaces Pili are the main mechanism by which bacteria adhere to human cells. They are fibers that extend from the surface of bacteria that mediate attachment to specific receptors on cells. Glycocalyx is a polysaccharide “slime layer” secreted by some strains of bacteria that mediates strong adherence to certain structures such as heart valves, prosthetic implants, and catheters. 3. Invasion, Inflammation, & Intracellular Survival Invasion of tissue is enhanced by enzymes secreted by bacteria. For example, 2 Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ Hyaluronidase produced by Streptococcus pyogenes degrades hyaluronic acid in the subcutaneous tissue, allowing the organism to spread rapidly. Coagulase, which accelerates the formation of a fibrin clot from its precursor, fibrinogen (this clot may protect the bacteria from phagocytosis by walling off the infected area and by coating the organisms with a layer of fibrin). IgA protease degrades secretory IgA, allowing bacteria to attach to mucous membranes. Leukocidins, which can destroy both neutrophilic leukocytes and macrophages. In addition to these enzymes, several virulence factors contribute to invasiveness by limiting the ability of the host defense mechanisms, especially phagocytosis, to operate effectively. The capsule surrounding bacteria is antiphagocytic (i.e., it retards the phagocyte from ingesting the organism). Inflammation is an important host defense induced by the presence of bacteria in the body. There are two types of inflammation, pyogenic and granulomatous, and bacteria typically elicit one type or the other. Pyogenic inflammation, the host defense against pyogenic (pus-producing) bacteria such as S. pyogenes, consists of neutrophils (and antibody and complement). Granulomatous inflammation, the host defense against intracellular, granuloma-producing bacteria, such as Mycobacterium tuberculosis, consists of macrophages and CD4- positive T cells. The type of inflammatory lesion is an important diagnostic criterion. Bacteria can evade our host defenses by a process called intracellular survival (i.e., bacteria that can live within cells are protected from attack by macrophages and neutrophils). Note that many of these bacteria (e.g., M. tuberculosis) are not obligate intracellular parasites (which can grow only within cells), but rather have the ability to enter and survive inside cells. These bacteria use several different mechanisms to allow them to survive and grow intracellularly. These include (1) inhibition of the 3 Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ fusion of the phagosome with the lysosome, which allows the organisms to avoid the degradative enzymes in the lysosome; (2) inhibition of acidification of the phagosome, which reduces the activity of the lysosomal degradative enzymes; and (3) escape from the phagosome into the cytoplasm, where there are no degradative enzymes. 4. Toxin Production The second major mechanism by which bacteria cause disease is the production of toxins. A comparison of the main features of exotoxins and endotoxins is shown in the table below: 5. Immunopathogenesis In certain diseases, such as rheumatic fever and acute glomerulonephritis, it is not the organism itself that causes the symptoms of disease but the immune response to the 4 Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ presence of the organism. For example, in rheumatic fever, antibodies are formed against the M protein of Str. pyogenes, which cross-react with joint, heart, and brain tissue. Inflammation occurs, resulting in the arthritis, carditis, and chorea that are the characteristic findings in this disease. Typical Stages of an Infectious Disease: 1. The incubation period is the time between the moment the person is exposed to the microbe (or toxin) and the appearance of symptoms. 2. The prodrome period is the time during which nonspecific symptoms occur. 3. The specific-illness period is the time during which the characteristic features of the disease occur. 4. The recovery period, also known as the convalescence period, is the time during which symptoms resolve and health is restored. After the recovery period, some people become chronic carriers, in which the organisms continue to grow with or without producing symptoms in the host and in others latent infections, after which reactivation of the growth of the organism and recurrence of symptoms may occur. Some people have subclinical infections (i.e., the individual remains asymptomatic although infected with the organism). The presence of antibodies reveals that a prior infection has occurred. 5 Theoretical Medical microbiology L-8 & L-9 __________________________________________________________________________ 6