Transmission of Infectious Disease: Role of Virulence Factors in Bacterial Invasiveness

1. Transmission of Infectious Disease: Role of Virulence Factors in Bacterial Invasiveness

2. General Definitions

3. Normal Flora • Microorganisms that are associated with a host, established at a particular anatomical location and don’t harm their host • Important part of innate immunity • Compete for space and nutrients with harm harmful organisms • When displaced from normal site to other areas  may cause disease • Example: Staphylococcus aureus in nose and throat can enter a wound and cause serious infections

4. Commensalism - the microorganism (commensal) benefits, while the host is neither harmed nor helped • The microorganism shares the same food source with the host • The microorganism is not directly dependent on the metabolism of the host • The microorganism causes no particular harm to host

5. Example • the common nonpathogenic strain of Escherichia coli lives in the human colon; • this facultative anaerobe uses oxygen creating an anaerobic environment in which obligate anaerobes (e.g. bacteroids) can grow. • The bacteroids benefit but the E. coli derives no obvious benefit or harm.

6. Mutualism • There is some reciprocal benefit to both partners • The microorganism (mutualist) and host are metabolically dependent upon each other • Syntropism is a mutually beneficial relationship in which each organism provides one or more growth factors, nutrients or substrates for the other organism; • also referred to as cross-feeding or the satellite phenomenon • Example: Intestinal flora synthesizing vitamin K and B complex vitamins for host

7. Parasitism - relationship in which a symbiont harms or lives at the expense of a host • Host - the body of the animal in which the parasite lives; • it provides the microenvironment that shelters and supports the growth and multiplication of the parasitic organism

8. Opportunist: • Lack ability to cause disease during health, but may invade following illness or suppression

9. Nosocomial infections • Infections acquired during hospitalization • Caused by opportunists that make up our normal flora • Endogenous disease - a disease caused by the host’s own microbiota because the host’s resistance has dropped

10. Gnotobiotic animals • Germ-free animals • Derived from caesarian section and rearing in a strict environment • Make valuable models for investigating immune responses and prevention of opportunistic infections

11. Pathogenicity • Ability of microbes to cause disease in the host it infects

12. Virulence • Extent of pathogenicity • Capacity to cause disease • Related to severity of disease in the host

13. Communicable diseases • Contagious • Transmissible from one host to another

14. Endemic disease • Persistent disease in a defined geographical area • Examples: • Rhinoviruses • Malaria

15. Parasite - usually the smaller of the two organisms; it is metabolically dependent on the host • Ectoparasite - lives on the surface of the host

16. Endoparasite - lives within the host • Final host - the host on (or in) which the parasite either gains sexual maturity or reproduces • Intermediate host - a host that serves as a temporary but essential environment for parasite development

17. Transfer host - a host that is not necessary for development but that serves as a vehicle for reaching the final host • Reservoir host - an organism (other than a human) that is infected with a parasite that can also infect humans

18. Infectious Disease Caused by Parasites • Infection - the state occurring when a parasite is growing and multiplying on or within a host

19. Infectious disease - a change from a state of health as a result of an infection by a parasitic organism • Adverse affect on the function of part or all of the host body as a result of the presence of a parasite or its toxic products • Pathogen - any parasitic organism that produces an infectious disease • Pathogenicity - the ability of a parasitic organism to cause a disease

20. Latency • When no symptoms present themselves • Intermittent latency • Herpes simplex virus (HSV) • Lies dormant in neural tissue and is induced to replicate by various factors including intense sunlight and stress • Quiescent latency • Persistence over very long periods of time (many years) • Varicella zoster • Chickenpox in children • Shingles in the elderly

21. Outcome of Host-Parasite Relationships

22. The final outcome of host-parasite relationships • Dependent on three factors: • The actual number of parasites in the body • How virulent the parasite is • How effective the host’s resistance is to infection

23. Disease often incurred if parasite is particularly virulent, even if the host has high resistance • Disease also incurred if virulence isn’t particularly intense, but the host’s resistance is weakened • Age • Illness • Immunosuppressive drugs

24. What Determines Virulence?

25. Virulence – a measure of pathogenic intensity determined by three properties of the pathogen: • Invasiveness – organism’s ability to penetrate the first line of defense and spread to adjoining tissues in the host • Infectivity – organism’s ability to establish a primary site of infection • Pathogenic potential – organism’s ability to induce morbid symptoms, determined by toxigenicity

26. What is toxigenicity? • Refers to organisms ability to produce toxic compounds (toxins) that are harmful and cause disease • Toxins = specific metabolic products of pathogen • Exotoxins • Endotoxins • Leukocidins • Hemolysins

27. LD50 and ID50 • LD50 • Lethal dose 50 • Number of pathogens required to kill 50% of subjects in a given time period • ID50 • Infectious dose 50 • Number of pathogens required to infect 50% of subjects

28. Components Influencing Infectious Disease

29. Transmissibility of the pathogen - involves initial transport to the host • Direct contact - coughing, sneezing, body contact (shaking hands, kissing) • Indirect contact – deposition into an environmental medium including soil, water, food and bedding • Inanimate object that harbor and transmit disease = fomites • Vectors - living organisms that transmit a pathogen from one host to another • Mosquitoes (Malaria, West Nile Virus) • Tick (Rocky Mountain spotted fever, Lyme disease) • Flea (Plague)

30. Zoonoses • Disease which are mainly prevalent in an animal population but can be transferred to humans • Rabies • Plaque • Brucellosis • Tularemia

31. Attachment and colonization (multiplication) by the pathogen • Pathogen must be able to adhere to and colonize host cells and tissue; • this is mediated by special molecules or structures called adhesins • Examples of adhesins • Filamentous hemagglutinin of Bordetella pertussis (binds to cilia of RT) • Fimbriae, pili • Glycocalyx (dental plaque) • Lectin • Capsule • S layer • Slime layer • Teichoic and lipoteichoic acids

32. Adhesins bind to host cell receptors • Examples: fibronectin, laminin, vitronectin, sialoproteins (found in host’s extracellular matrix) • Pathogen must compete with normal microbiota for essential nutrients

33. Invasion and Evasion of Host Defense Mechanisms

34. Invasion of the pathogen • Requires penetration of the host’s epithelial cells or tissues • Invasiveness = features that enable pathogens to escape immune detection/defenses and cause overt infection

35. Portals of Entry • Each infectious organism has its own portal of entry and portal of exit from the host • Entry: • Respiratory tract via nose and throat • M tuberculosis can survive in dried sputum for weeks • Gastrointestinal tract via mouth • S. typhi multiply only I cells of intestinal mucosa • Skin and mucus membranes • Genitourinary system (STD) • Blood (insects, transfusions, needles) • Exit: Usually the same as the portals of entry

36. Pathogen-associated mechanisms involve the production of lytic substances that may: • Attack the ground substance and basement membranes of integuments and intestinal linings • Depolymerize carbohydrate-protein complexes between cells or on cell surfaces • Disrupt cell surfaces and extracellular matrix

37. Passive mechanisms of entry involve: • Breaks, lesions, or ulcers in the mucous membranes • Wounds, abrasions, or burns on the skin surface • Arthropod vectors that penetrate when feeding • Tissue damage caused by other organisms • Endocytosis by host cells

38. Gaining of access to deeper tissues • Penetration into the circulatory system • Growth and multiplication of the pathogen - pathogen must find an appropriate environment • pH • Oxygen tension • Nutrient availabililty (including specialized growth factors) • Intracellular growth • Mycobacterium tuberculosis in alveolar macrophages • Extracellular growth • Pyogenic infections – pus formation in extracellular spaces (pyogenic streptococci – S. pyogenes)

39. Dissemination by Evasion • Pathogens spread throughout the host tissue and sometimes even gain entry into lymphatic capillaries and then eventually into the circulation • Localized infection = limited • Systemic dissemination = multiple organs • Enhanced by microbial products and enzymes (virulence factors)

40. Capsules and fimbriae – antiphagocytic, requires antibodies for opsonization • Leukocidins - extracellular enzymes that kill phagocytic leukocytes by causing degranulation of lysosomes • Hemolysins - extracellular enzymes that kill erythrocytes by forming a pore (iron released) • Streptolysin O – inactivated by oxygen, beta hemolysis when incubated anaerobically (S. pyogenes) • Streptolysin S – not oxygen sensitive, beta hemolysis under aerobic conditions • If phagocytosed, acts as a leukocidin and kills macrophages

41. Coagulase – clots fibrinogen in plasma, protecting pathogen from phagocytosis and other host defenses • Collagenase – Degrades collagen in connective tissue promoting the spread of the pathogen • Deoxyribonuclese – reduces viscosity of exudates, improving pathogen mobility

42. Elastase – degrades laminin in ECM • Exotoxin B – aka pyrogenic exotoxin b – protease • Hydrogen peroxide and ammonia – damage to respiratory and urogenital systems

43. Hyaluronidase – degrades hyaluronic acid in intercellular ground substances holding cells together – increases mobility • IgA protease – Degrades antibody (IgA isotype) into Fab and Fc fragments • Lecithinase – degradation of lecithin in PM (phosphatidylcholine)

44. Protein A – binds IgG at Fc, prevents C’ activation • Streptokinase (fibrinolysin, staphylokinase)– binds plasminogen and induces production of plasmin, and digestion of fibrin clots – increasing mobility of pathogen from clotted areas

45. TOXINS

46. Toxigenicity - the capacity of an organism to produce a toxin • Intoxications – diseases caused as a result of toxin produced inside the body • Toxin - a specific substance, often a metabolic product of the organism, that damages the host in some specified manner • Toxemia - symptoms caused by toxins if they enter the blood of the host

47. Two main categories of toxins • Exotoxins • Endotoxins

48. EXOTOXINS

49. Characteristics of Exotoxins • Soluble, heat-labile proteins produced by and released from an organism during growth and replication • May damage the host at some remote site • Genes that encode exotoxins are located on chromosomes, plasmids and bacteriophages

50. Make up most lethal substances yet identified • Have specific disease associations and specific effects in the host • Often named after the disease that they cause (e.g. cholera toxin, diphtheria toxin) • Stimulate strong immune responses • Highly immunogenic • Induce production of neutralizing antibodies (antitoxins) • Inactivated by a variety of chemicals to form immunogenic toxoids (e.g. formaldehyde, iodine) • Do not cause fever in the host with exception of superantigens