Bacterial Pathogenesis & Infection Properties PDF

Properties of Bacterial Pathogens and Pathogenesis of Infection -Bacterial infection results from a disturbance in the balance between bacterial virulence and host resistance. The “objective” of bacteria is to multiply rather than to cause disease. The growth rate of bacteria exceeds that of most e...

Properties of Bacterial Pathogens and Pathogenesis of Infection -Bacterial infection results from a disturbance in the balance between bacterial virulence and host resistance. The “objective” of bacteria is to multiply rather than to cause disease. The growth rate of bacteria exceeds that of most eukaryotic cells. The human body carries 10 times more bacteria than human cells and only 50 out of the more than 1000 types of bacterial species we carry cause disease. Definitions: -Microbiota: Microbial flora harbored by normal, healthy individuals. -Adherence (attachment): The process by which bacteria stick to the surfaces of host cells. After bacteria enter the body, adherence is a major initial step in the infection process. Colonization: is the presence of multiplying bacteria on a body surface without causing disease. -Infection: Invasion and Multiplication of an infectious agent within the body. -Invasion: The process whereby bacteria enter host cells or tissues and spread in the body. Normal Human Microbiota: The normal microbiota denotes the population of microorganisms that inhabit the skin and mucous membranes of healthy normal persons. The normal microbiota provides a first line of defense against microbial pathogens, assists in digestion, and contributes to maturation of the immune system. The skin and mucous membranes always harbor a variety of microorganisms that can be divided into (1) resident microbiota, which are fixed types of microorganisms regularly found in a given area at a given age. If disturbed, resident flora reestablish themselves, and (2) transient microbiota, which are nonpathogenic or potentially pathogenic microorganisms that inhabit the skin or mucous membranes for hours, days, or weeks. Classification of Pathogens: Pathogens can be classified as either primary pathogens or opportunistic pathogens. 1. Primary pathogen: can cause disease in a normal healthy host. Example: Mycobacterium tuberculosis (tuberculosis). 2. Opportunistic pathogen: can cause disease only in situations that compromise the host’s defenses (e.g., patients undergoing chemotherapy, people with immunodeficiencies (e.g. AIDS), burn patients). Other members of the normal microbiota can also cause opportunistic infections when normal flora change their habitat, for example: a. Staphylococcus epidermidis is a member of the normal microbiota of the skin, where it is generally avirulent. In hospitals, it can also grow in biofilms that form on catheters, implants, or other devices that are inserted into the body during surgical procedures. Once inside the body, S. epidermidis can cause serious infections such as endocarditis. b. E. coli normally found in the large intestine can cause a urinary tract infection if it enters the urinary tract. c. viridans Streptococci may produce infective endocarditis in a previously damaged heart valve (by congenital disease or rheumatic fever), if the organism reaches the blood stream after tooth extraction or tonsillectomy. The infectious process -The infectivity of the pathogen (capacity to initiate infection) is related to: 1) Dose of the pathogen (the infective dose); the number of bacteria required to cause disease. 2) Its growth phase (bacteria are more infective in the log phase than the lag phase). 3) Its virulence. -The pathogen must be able to gain entry to the host, travel to the location where it can establish an infection, evade or overcome the host’s immune response, and cause damage (i.e., disease) to the host. -In the body, most bacteria cause infection first by attaching or adhering to host cells, usually epithelial cells. After the bacteria have established a primary site of infection, they multiply and spread directly through tissues or via the lymphatic system to the bloodstream. This allows bacteria to spread widely in the body and permits them to reach tissues particularly suitable for their multiplication. Bacterial Virulence factors Many factors determine bacterial virulence or the ability to cause infection and disease. These factors help the microorganisms to: 1) invade the host, 2) evade host defenses, and 3) cause disease. The following are types of virulence factors: a- Adherence factors b- Invasion c- Antiphagocytic factors d- Toxin production e- Extracellular enzymes f- Bacterial biofilms g- Intracellular survival a- Adherence factors: Certain bacteria have specialized structures e.g. pili, that help their adherence to the host cell mucous membranes thus allow them to start the disease process. If they did not adhere they will be swept away e.g. teichoic acid causes adherence of the streptococci to buccal epithelial cells. b- Invasion: Is the ability of bacteria to invade the tissue, and multiply. c- Antiphagocytic factors: Some pathogens evade phagocytosis or leucocyte microbicidal mechanisms. For example, Staphylococcus aureus has surface protein A, which binds to the Fc portion of IgG. Other pathogens have polysaccharide capsules that impede phagocytosis (eg, S. pneumoniae and N. meningitidis); S. pyogenes has M protein. d- Toxin production: Toxins produced by bacteria are generally classified into two groups: endotoxin (LPS), which is present in the outer membrane of Gram-negative rods, and exotoxins that are secreted by bacterial cells. e- Extracellular enzymes: These are produced by pathogens to play important roles in the infectious process. Example: Staphylococcus aureus produces coagulase, which coagulates plasma. Coagulase contributes to the formation of fibrin walls around staphylococcal lesions, which helps them persist in tissues. Hyaluronidases are enzymes that hydrolyze hyaluronic acid, a constituent of the ground substance of connective tissue (eg, staphylococci, streptococci). IgA proteases destroy mucosal IgA secreted by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. f- Bacterial biofilms: A biofilm is an aggregate of bacteria attached to a solid surface or to each other and encased in an exopolysaccharide matrix. The bacteria in the exopolysaccharide matrix are protected from the host’s immune mechanisms. This matrix also functions as a diffusion barrier for some antimicrobials. Biofilms are important in human infections that are persistent and difficult to treat. g- Intracellular survival: Some bacteria (eg, Mycobacterium tuberculosis) live and grow intracellularly within polymorphonuclear cells, macrophages, or monocytes. Evading intracellular killing by phagocytic cells can be accomplished by several mechanisms: they may avoid entry into phagosome and live within the cytosol of the phagocyte; they may prevent phagosome–lysosome fusion and live within the phagosome; or they may be resistant to lysosomal enzymes and survive within the phagolysosome. Transmission of infection (Figure 1) Bacteria can adapt to a variety of environments which constitute the reservoir, whether external environment or inside a host. An anatomic site through which pathogens can pass into host tissue is called a portal of entry, e.g., the respiratory tract, oral cavity, genital, and urinary tracts. Pathogens may also enter the body through a breach in the protective barriers of the skin and mucous membranes (e.g., wounds, insect bites, animal bites, needle pricks). There must be a mode of transmission of bacteria to a new host. Different modes of transmission include the following: 1. Contact transmission includes direct contact or indirect contact. a. Direct contact can be categorized as vertical (mother to child), horizontal (touching, kissing, sexual), or droplet transmission. When an individual coughs or sneezes, small droplets of mucus that may contain pathogens are ejected. This leads to direct droplet transmission of a pathogen to a new host over distances of one meter or less (e.g. Influenza viruses). b. Indirect contact transmission involves inanimate objects that become contaminated by pathogens from an infected individual or reservoir. Transmission occurs indirectly when a new susceptible host later touches the fomite and transfers the contaminated material to a susceptible portal of entry. 2. Vehicle Transmission The term vehicle transmission refers to the transmission of pathogens through vehicles such as water, food, and air. 3. Vector Transmission Diseases can also be transmitted by a mechanical or biological vector (typically an arthropod) that carries the disease from one host to another. For a pathogen to persist, it needs to be transmitted to a new host, leaving the infected host through a portal of exit. Similar to portals of entry, the most common portals of exit include the skin and the respiratory, urogenital, and gastrointestinal tracts.