Pathogenesis of Bacterial Infections 2142022 Pathogenecity Pathogenicity is

Pathogenesis of Bacterial Infections 2/14/2022

Pathogenecity • Pathogenicity is the ability to produce disease in a host organism. • acute, • chronic, • or recurrent. 2/14/2022

Pathogen • A pathogenic microorganism is defined as one that causes or is capable of causing disease. • immune-compromised host. • Immunocompetent host 2/14/2022

Infection • Infection: The invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present within the body. • An infection may cause no symptoms and be subclinical, or it may cause symptoms and be clinically apparent. • localized, • systemic (bodywide). 2/14/2022

• endemic infections are those that occur at a persistent, usually low level in a certain geographic area, • epidemics are those infections that occur at a much higher rate than usual, and • pandemics are those infections that spread rapidly over large areas of the globe. 2/14/2022

Opportunistic Pathogens • Opportunistic pathogens are those that rarely, if ever, cause disease in immunocompetent people but • can cause serious infection in immunocompromised patients. frequent members of the body's normal flora. 2/14/2022

Infection Process • The infection process in general, divided into several stages: 1) Entry into the host with evasion of host primary defences. 2) Adhesion of the microorganism to host cells 3) Propagation of the organism. 4) Damage to host cells by toxins or an inflammatory response. 5) Evasion of host secondary defenses. • The pathogenicity of a microorganism depends on its success in completing some or all of these stages. 2/14/2022

Virulence • Virulence is a quantitative measure of pathogenicity and is measured by the number of organisms required to cause disease. • The 50% lethal dose (LD 50) is the number of organisms needed to kill half the hosts, • 50% infectious dose (ID 50) is the number needed to cause infection in half the hosts. – Organisms with a lower LD 50 (or ID 50) are said to be more virulent than those with a higher LD 50 (or ID 50) because fewer organisms are needed to cause death or disease. 2/14/2022

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• The infectious dose of an organism required to cause disease varies greatly among the pathogenic bacteria. For example, Shigella and Salmonella both cause diarrhea by infecting the gastrointestinal tract, but the infectious dose of • Shigella is less than 100 organisms, • whereas the infectious dose of • Salmonella is on the order of 100, 000 organisms. 2/14/2022

Signs and symptoms • An infection that results in disease, a noticeable impairment of body function, is called an infectious disease. • symptoms are the subjective effects of the disease experienced by the patient, such as pain and nausea, whereas signs are the objective evidence, such as rash, pus formation, and swelling. 2/14/2022

• Signs • Symptoms 2/14/2022

Infection process • The infection process in general, divided into several stages: • 1) Entry into the host with evasion of host primary defenses • 2) Adhesion of the microorganism to host cells • 3) Propagation of the organism • 4) Damage to host cells by toxins or an inflammatory response • 5) Evasion of host secondary defenses. • The pathogenicity of a microorganism depends on its success in completing some or all of these stages. 2/14/2022

Mechanisms of Bacterial Pathogenicity Two broad qualities of pathogenic bacteria underlie the means by which they cause disease: 1. Invasiveness is the ability to invade tissues. It encompasses mechanisms for colonization (adherence and initial multiplication), production of extracellular substances which facilitate invasion (invasins) and ability to bypass or overcome host defense mechanisms. 2/14/2022

2. Toxigenesis is the ability to produce toxins. Bacteria may produce two types of toxins called exotoxins and endotoxins. 2/14/2022

Determinants of Bacterial Pathogenesis • Transmission • human-to-human and nonhuman-to-human 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. • Human diseases for which animals are the reservoir are called zoonoses. 2/14/2022

• • • Portals of entry the respiratory tract, gastrointestinal tract, skin, and genital tract. 2/14/2022

Portal of Entry Pathogen Disease Respiratory tract Streptococcus pneumoniae Pneumonia Neisseria meningitides Meningitis Haemophilus influenzae Meningitis Mycobacterium tuberculosis Tuberculosis Shigella dysenteriae Dysentery Salmonella typhi Typhoid fever Vibrio cholerae Cholera Clostridium tetani Tetanus Rickettsia rickettsii Rocky Mountain spotted fever Neisseria gonorrhoeae Gonorrhea Treponema pallidum Syphilis Chlamydia trachomatis Urethritis Gastrointestinal tract Skin Genital tract 2/14/2022

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. 2/14/2022

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• pili of Neisseria gonorrhoeae and E. coli mediate the attachment of the organisms to the urinary tract epithelium, and the glycocalyx of Staphylococcus epidermidis and certain viridans streptococci allow the organisms to adhere strongly to the endothelium of heart valves 2/14/2022

Biofilm 2/14/2022

Quorum Sensing • cell to cell communication; at a certain bacterial density the bacteria begin to make signals to produce their virulence factors. 2/14/2022

Invasion • Collagenase and Hyaluronidase produced by Streptococcus pyogenes degrades hyaluronic acid in the subcutaneous tissue, allowing the organism to spread rapidly. • Ig. A protease degrades secretory Ig. A, allowing bacteria to attach to mucous membranes. • The capsule surrounding bacteria is antiphagocytic, i. e. , it retards the phagocyte from ingesting the organism. • Leukocidins, which can destroy both neutrophilic leukocytes and macrophages. 2/14/2022

Antiphagocytotic factors • capsule of Str. pneumoniae and Neisseria meningitidis. • cell wall proteins of the gram-positive cocci, such as the M protein of the group A streptococci (Streptococcus. pyogenes) is antiphagocytic (preventing opsonization by C 3 b), • protein A of Staphylococcus aureus binds to Ig. G and prevents (opsonisation) the activation of complement. 2/14/2022

Bacterial Toxins • Some bacteria cause disease by producing toxins, of which there are two general types: Exotoxins Endotoxins. 2/14/2022

Exotoxins • These include some of the most poisonous substances known. • It is estimated that as little as one microgram of tetanus exotoxin can kill an adult human. • Exotoxins are polypeptides secreted They are produced by both grampositive and gram-negative bacteria, 2/14/2022

• Many exotoxins have an A–B subunit structure • Exotoxins are antigenic and induce antibodies called antitoxins. • Exotoxins can be modified to form toxoids, which are antigenic but not toxic. Toxoids, such as tetanus toxoid, are used to immunize against disease. 2/14/2022

Endotoxins • Endotoxins are lipopolysaccharides (LPS) located in the outer membrane only of gramnegative bacteria. • Endotoxins are poorly antigenic, do not induce antitoxins, and do not form toxoids. 2/14/2022

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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 is the time during which symptoms resolve and health is restored. After the recovery period, some people become chronic carriers of the organism. 2/14/2022

Next Lecture • Normal Flora 2/14/2022