Ch35 Pathogenicity and Infection Lecture Notes PDF

35 Pathogenicity and Infection 1 Pathogenicity Drives Infectious Diseases Infection Infectious disease Host Parasites Pathogens – Primary (Frank) – Opportunistic Pathogenicity 2 The infectious disease process is a chain of five links Chain of events for a successful infection requires – Specific age...

35 Pathogenicity and Infection 1 Pathogenicity Drives Infectious Diseases Infection Infectious disease Host Parasites Pathogens – Primary (Frank) – Opportunistic Pathogenicity 2 The infectious disease process is a chain of five links Chain of events for a successful infection requires – Specific agent – Substantial virulence – Exposed to – Susceptible host – Sufficient doses 3 Course of infectious disease #Exposure contrast source and reservoir Sources of pathogens can be – Animate (other humans or animals) infections passed from animal to human are termed zoonoses many examples of zoonoses ….. – Inanimate (water, soil, food) Reservoir = natural environmental location in which the pathogen normally resides…..birds (West nile) Brackish water (Vibrio cholera) Source = site from which host is directly infected. Reservoir can be the source of a disease 4 Course of infectious disease #Virulence Virulence factors and Toxigenicity Virulence factor = Needed to adapt, outcompete host and evade immune defenses Some microbes are toxigenic produce toxins Toxin – specific substance that damages host Intoxications – diseases that result from entry of a specific preformed toxin into host Toxemia – condition caused by toxins in the blood of host 5 Indicators of the Process of Infectious Disease Signs and Symptoms are key Infectious disease infection with viruses, bacteria, fungi, protozoa, and helminths (prions???) Signs –objective changes in body that can be directly observed Symptoms –subjective changes experienced by patient Disease syndrome –set of characteristic signs and symptoms 6 Course of Infectious Disease has a discernible pattern incubation period – period after pathogen entry, before signs and symptoms prodromal stage – onset of signs and symptoms – not clear enough for diagnosis period of illness – disease is most severe, signs and symptoms convalescence – signs and symptoms begin to disappear 7 Course of infectious disease #Infectious Dose Initial inoculum and virulence determine rate of disease progression and severity Measure of infectivity (Dose) 1) Infectious dose 50 (ID50) 2) Lethal dose 50 (LD50) – dose that kills 50% of experimental animals within a specified period 3) Cytopathology – cellular changes – Can be used to observe cells in tissue culture for death rates rather than entire organisms 4) Examining virulence factors and their release 8 Course of infectious disease #Host Susceptibility Two main factors – defense mechanisms of host (discussed in Chs. 33 and 34) – pathogenicity of pathogen Nutrition, genetic predisposition, and stress also play a role in host susceptibility to infection Disease Outcome = Host Defenses / Pathogenicity of agent 9 35.2 Virulence 1. Identify and describe the features that allow microorganisms to overcome host resistance and immunity 2. Discuss the strategies microorganisms have evolved to exploit human cells and tissues as resources for their survival 3. Compare the molecular mechanisms by which microorganisms adhere to and invade human cells and tissues 4. Illustrate the mechanisms by which microbial toxins impact human cells 5. Model disease processes and explain virulence 10 Virulence defines a pathogen’s success Degree or intensity of pathogenicity Virulence factors – determine the degree to which the pathogen causes damage, invasion, infectivity Determined in part by pathogen’s ability to survive outside host 11 Pathogenicity Islands encode virulence factors Major virulence factors on large segments on chromosomal or plasmid DNA – increase bacterial virulence – absent in nonpathogenic members – common sequence characteristics insertion-like sequences for mobility G + C content different from bacterial genome several open reading frames – can be spread through horizontal transfer of virulence genes to bacteria 12 13 Virulence Factors Animal model systems may be used to determine role of virulence factor in disease process Determined by characteristics of the pathogen – adherence and colonization – invasion 14 Adherence and Colonization First step in disease is entrance and attachment Portal of entry – skin, respiratory, gastrointestinal, urogenital systems, or conjunctiva of eye – vector borne, sexual contact, blood transfusion, or organ transplant Adherence – mediated by special molecules called adhesins Colonization – a site of microbial reproduction on or within host – does not necessarily result in tissue invasion or damage 15 Adherence structures – pili, fimbriae (adhesion molecules on bacterium’s Attachment and Colonization cell surface) bind complementary receptor sites on host cell surface Colonization – a site of microbial reproduction on/in host – does not necessarily result in tissue damage 16 Invasion Invasion - ability to spread to adjacent tissues Penetration can be active or passive – active occurs through lytic substances Which attack the extracellular matrix and basement membranes – examples in integuments and intestinal linings degrade carbohydrate-protein complexes between cells disrupt host cell surface – passive (e.g., skin lesions, insect bites, wounds) spread to deeper tissues involves production of specific products and/or enzymes that promote spreading 17 18 Invasion Once in circulatory system, bacteria have access to all organs and systems – bacteremia – presence of viable bacteria in the blood – septicemia –pathogens or their toxins in the blood varies among pathogens – e.g., Clostridium tetani (tetanus) produces a number of virulence factors but is non-invasive – e.g., Bacillus anthracis (anthrax) and Yersinia pestis (plague) also produce many virulence factors and are highly invasive – e.g., Streptococcus spp. span the spectrum of virulence factors and invasiveness 19 Toxigenicity II - Exotoxins Soluble, heat-labile, proteins Secreted into surroundings as pathogen grows Most exotoxin producers are Gram-negative Often travel from site of infection to other tissues or cells where they exert their effects Usually synthesized by specific bacteria that have toxin genes in their plasmids or prophage DNA Among the most lethal substances known Are highly immunogenic Stimulate production of neutralizing Ab (antitoxins) Chemically inactivated to form immunogenic toxoids – e.g., tetanus toxoid 20 Types of Exotoxins AB exotoxins – composed of two subunits A subunit – responsible for toxic effect B subunit – binds to specific target cell Specific host site exotoxins Membrane-disrupting exotoxins Superantigens 21 22 Superantigens Stimulate ~30% of T cells of the immune system – causes the T cells to overexpress and release cytokines Example is staphylococcal enterotoxin B – results in failure of multiple host organs allowing time for the microbe to disseminate 23 Endotoxins Lipopolysaccharide (LPS) in Gram-negative cell wall can be toxic to specific hosts – called endotoxin because it is an endogenous (part) of the bacterium and released when organism lyses some is also released during multiplication – toxic component is the lipid portion, lipid A 24 25 Heat stable Endotoxins Toxic (nanogram amounts) Weakly immunogenic Generally similar, despite source Cause general system effects – fever, weakness, diarrhea, inflammation, intestinal hemorrhage, and fibrinolysis, the enzymatic breakdown of fibrin, the major protein component of blood clots 26 Mycotoxins Secondary metabolites of fungi – common contaminants of food crops – Aspergillus flavus and A. parasiticus produce carcinogenic aflatoxin – Stachybotrys produce tissue-damaging satratoxins – Claviceps purpurea (ergot) produce hallucinogen lysergic acid (LSD) 27 Biofilm Development Biofilm growth is physiologically different from planktonic growth – may cause chronic infection – increases virulence – become less sensitive to antibiotics – make cells in biofilm more resistant to host defense (“frustrates” phagocytes) 28 Question 1 - Attendance 21 Colonization specifically refers to the multiplication of a pathogen on or within a host, and includes the resulting tissue invasion and damage. True or False 29 Resisting Host Defenses Most microbes eliminated before they can cause disease due to immune system Successful pathogen evades immune system Numerous mechanisms for both viral and bacterial pathogens 30 Resisting Host Defenses Infection of immune system cells, diminishing function Fuse with adjacent cells to prevent exposure to antimicrobial proteins in host Capsules prevent phagocytosis Mutations change antigenic sites or alter expression of antigens – through downregulation or phase variation Produce substances that resemble host tissue Produce proteases that degrade host proteins Special proteins that interfere with host defenses 31 Resisting Host Defenses Production of decoy proteins to bind available neutralizing antibodies Lengthened O-chains to prevent host detection or lysis Some survive inside host cells – eject themselves from cell to cell using host actin 32 Exposure and Pathogen Transmission Initial transmission of pathogen to host – evidence suggests correlation between mode of transmission and degree of virulence direct contact less virulent vector-borne highly virulent in human host; relatively benign in vector greater ability to survive outside host more virulent Transmission from host to host Transmission alone not enough for infection to occur – Tropism - pathogen must make contact with appropriate host tissue determined by specific cell surface receptors 33 34 Pathogen Transmission Five main modes of transmission – airborne – contact – vehicle – vector borne – vertical 35 Airborne Transmission Pathogen suspended in air and travels 1 meter Droplet nuclei – small particles (1–4 m diameter) – can remain airborne for long time – can travel long distances – usually propelled from respiratory tract of source organisms by sneezing, coughing, or vocalization Dust particles also important route of airborne transmission 36 Contact Transmission Coming together or touching of source/reservoir and host Direct contact (person-to-person) – physical interaction between source/reservoir and host – e.g., kissing, touching, and sexual contact Indirect contact – involves an intermediate (usually inanimate) – e.g., eating utensils, bedding Droplet spread – large particles (>5 m) that travel