![Cell Wall Components
M protein: Found on cell surface and
fimbriae of Streptococcus pyogenes.
Mediates attachment and helps resist
phagocytosis. M-protein is heat and
acid resistant
Waxes [ Mycolic Acid]: In cell wall
of Mycobacterium tuberculosis helps
resist digestion after phagocytosis and
can multiply inside WBC.](https://image.slidesharecdn.com/lecture6-bacteria-phathogenesis-240519191135-808477e6/85/Lecture-6-Bacteria-Pathathogenesis-ppt-42-320.jpg)
Lecture 6- Bacteria- Pathathogenesis.ppt
- 2. Infection and Disease A. Definitions B. Generalized Stages of Infection C. Virulence Factors and Toxins
- 3. A. Definitions Disease and Infectious Disease • Disease • Any deviation from a condition of good health and well-being • Infectious Disease A disease condition caused by the presence or growth of infectious microorganisms or parasites
- 4. A. Definitions Pathogenicity and Virulence • Pathogenicity • The ability of a microbe to cause disease • This term is often used to describe or compare species • Virulence • The degree of pathogenicity in a microorganism • This term is often used to describe or compare strains within a species
- 5. Definitions Acute infection vs. chronic infection • Acute Infection • An infection characterized by sudden onset, rapid progression, and often with severe symptoms • Chronic Infection • An infection characterized by delayed onset and slow progression
- 6. Definitions Primary infection vs. secondary infection • Primary Infection • An infection that develops in an otherwise healthy individual • Secondary Infection • An infection that develops in an individual who is already infected with a different pathogen
- 7. Definitions Localized infection vs. systemic infection • Localized Infection • An infection that is restricted to a specific location or region within the body of the host • Systemic Infection • An infection that has spread to several regions or areas in the body of the host
- 8. Definitions Clinical infection vs. subclinical infection • Clinical Infection • An infection with obvious observable or detectable symptoms • Subclinical Infection • An infection with few or no obvious symptoms
- 9. Definitions Opportunistic infection • An infection caused by microorganisms that are commonly found in the host’s environment. This term is often used to refer to infections caused by organisms in the normal flora.
- 10. Definitions The suffix “-emia” • A suffix meaning “presence of an infectious agent” • Bacteremia = Presence of infectious bacteria • Viremia = Presence of infectious virus • Fungemia = Presence of infectious fungus • Septicemia = Presence of an infectious agent in the bloodstream
- 11. Definitions The suffix “-itis” • A suffix meaning “inflammation of” • Examples: –Pharyngitis = Inflammation of the pharynx –Endocarditis = Inflammation of the heart chambers –Gastroenteritis = Inflammation of the gastointestinal tract
- 12. Definitions Epidemiology • The study of the transmission of disease Communicable Disease • A disease that can be transmitted from one individual to another Noncommunicable Disease • A disease that is not transmitted from one individual to another
- 13. Definitions Endemic Disease • A disease condition that is normally found in a certain percentage of a population Epidemic Disease • A disease condition present in a greater than usual percentage of a specific population Pandemic Disease • An epidemic affecting a large geographical area; often on a global scale
- 14. Definitions Reservoir of Infection • The source of an infectious agent Carrier • An individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual Fomites • Any inanimate object capable of being an intermediate in the indirect transmission of an infectious agent
- 15. Definitions • Animal Vectors • An animal (nonhuman) that can transmit an infectious agent to humans • Two types: mechanical and biological • Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; e.g, the transmission of bacteria sticking to the feet of flies • Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; e.g, the transmission of malaria by infected mosquitoes
- 16. Definitions Direct Mechanisms of Disease Transmission • Directly From Person to Person • Examples: Direct Skin Contact Airborne (Aerosols)
- 17. Definitions Indirect Mechanisms of Disease Transmission • Examples: Food & Waterborne Transmission Fomites Animal Vectors
- 19. Pathogenicity - ability to cause disease Virulence - degree of pathogenicity Many properties that determine a microbe’s pathogenicity or virulence are unclear or unknown But, when a microbe overpowers the hosts defenses, infectious disease results!
- 20. Molecular Determinants of Pathogenicity Production and delivery of various factors Attachment to host tissues Replication and evasion of immunity Damage to host tissues
- 21. Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease
- 22. Portals of Entry 1. Mucus Membranes 2. Skin 3. Parentarel
- 23. 1. Mucus Membranes A. Respiratory Tract • microbes inhaled into mouth or nose in droplets of moisture or dust particles • Easiest and most frequently traveled portal of entry
- 24. Common Diseases contracted via the Respiratory Tract Common cold Flu Tuberculosis Whooping cough Pneumonia Measles Diphtheria
- 25. Mucus Membranes B. Gastrointestinal Tract • microbes gain entrance thru contaminated food & water or fingers & hands • most microbes that enter the G.I. Tract are destroyed by HCL & enzymes of stomach or bile & enzymes of small intestine
- 26. Common diseases contracted via the G.I. Tract Salmonellosis • Salmonella sp. Shigellosis • Shigella sp. Cholera • Vibrio cholorea Ulcers • Helicobacter pylori Botulism • Clostridium botulinum Clostridium botulinum
- 27. Fecal - Oral Diseases These pathogens enter the G.I. Tract at one end and exit at the other end. Spread by contaminated hands & fingers or contaminated food & water Poor personal hygiene.
- 28. Mucus Membranes of the Genitourinary System - STD’s Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Chlamydia Chlamydia trachomatis HIV Herpes Simplex II
- 29. Mucus Membranes D. Conjunctiva – • mucus membranes that cover the eyeball and lines the eyelid Trachoma • Chlamydia trachomatis
- 30. 2nd Portal of Entry: Skin Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms. Some microbes can gain entrance through openings in the skin: hair follicles and sweat glands, wound …etc
- 32. 3rd Portal of Entry: Parentarel Microorganisms are deposited into the tissues below the skin or mucus membranes Punctures and scratches injections bites surgery
- 33. Preferred Portal of Entry Just because a pathogen enters your body it does not mean it’s going to cause disease. pathogens - preferred portal of entry
- 34. Preferred Portal of Entry Streptococcus pneumoniae • if inhaled can cause pneumonia • if enters the G.I. Tract, no disease Salmonella typhi • if enters the G.I. Tract can cause Typhoid Fever • if on skin, no disease
- 35. Number of Invading Microbes LD50 - Lethal Dose of a microbes toxin that will kill 50% of experimentally inoculated test animal ID50 - infectious dose required to cause disease in 50% of inoculated test animals • Example: ID50 for Vibrio cholerea 108 cells (100,000,000 cells) • ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????
- 36. How do Bacterial Pathogens penetrate Host Defenses? 1. Adherence - almost all pathogens have a means to attach to host tissue Binding Sites adhesins ligands
- 37. Some cells use fimbriae to adhere. Fimbriae can play a role in tissue tropism. Example - attachment of Candida to vaginal epithelial cells
- 38. Adhesins and ligands are usually on Fimbriae Neisseria gonorrhoeae ETEC (Entertoxigenic E. coli) Bordetello pertussis
- 39. Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae. Alternatively, adhesins can consist of glycocalyx.
- 40. 2. Capsules Prevent phagocytosis attachment Streptococcus pneumoniae Klebsiella pneumoniae Haemophilus influenzae Bacillus anthracis Streptococcus mutans K. pneumoniae
- 41. Avoidance of Phagocytosis Capsules are Involved in avoidance of phagocyte- mediated recognition and attachment.
- 42. Cell Wall Components M protein: Found on cell surface and fimbriae of Streptococcus pyogenes. Mediates attachment and helps resist phagocytosis. M-protein is heat and acid resistant Waxes [ Mycolic Acid]: In cell wall of Mycobacterium tuberculosis helps resist digestion after phagocytosis and can multiply inside WBC.
- 43. 3. Enzymes Many pathogens secrete enzymes that contribute to their pathogenicity
- 44. Enzymes and toxins that harm eukaryotic cells.
- 45. A. Leukocidins Attack certain types of WBC’s 1. Kills WBC’s which prevents phagocytosis 2. Releases & ruptures lysosomes • lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage
- 46. B. Hemolysins - cause the lysis of RBC’s Streptococci
- 47. 1. Alpha (α) Hemolytic Streptococci - secrete hemolysins that cause the incomplete lysis or RBC’s Incomplete Lysis of RBC
- 48. 2. Beta (β) Hemolytic Streptococci - secrete hemolysins that cause the complete lysis of RBC’s Complete Lysis of RBC
- 49. 3. Gamma (γ) Hemolytic Streptococci - do not secrete any hemolysins
- 50. C. Coagulase - cause blood to coagulate Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses Staphylococcus aureus - are often coagulase positive Fibrinogen ----------------- Fibrin ( Clot)
- 51. D. Kinases - enzymes that dissolve blood clots 1. Streptokinase - Streptococci 2. Staphylokinase - Staphylococci Helps to spread bacteria - Bacteremia Streptokinase - used to dissolve blood clots in the Heart (Heart Attacks due to obstructed coronary blood vessels)
- 52. E. Hyaluronidase Breaks down Hyaluronic acid (found in connective tissues) “Spreading Factor” mixed with a drug to help spread the drug through a body tissue Streptococci, Staphylococci, Clostridia and pneumococci.
- 53. F. Collagenase Breaks down collagen (found in many connective tissues) Clostridium perfringens - Gas Gangrene • uses this to spread through muscle tissue
- 54. Severe gangrene caused by Clostridium perfringens. Source: Tropical Medicine and Parasitology, 1997 Tissue Damage Caused by Microbial Enzymes of Clostridium perfringens
- 55. G. Necrotizing Factor - causes death (necrosis) to tissue cells “Flesh Eating Bacteria” Necrotizing fasciitis
- 56. H. Lecithinase Destroys lecithin ( phosphatidylcholine) component of plasma membrane. Allowing pathogen to spread Clostridium perfringens
- 57. Summary of How Bacterial Pathogens Penetrate Host Defenses 1. Adherence 2. Capsule 3. Enzymes • A. leukocidins B. Hemolysins • C. Coagulase D. Kinases • E. Hyaluronidase F. Collagenase • G. Necrotizing Factor H. Lecithinase
- 58. 4. Toxins Poisonous substances produced by microorganisms toxins - primary factor - pathogenicity 220 known bacterial toxins • 40% cause disease by damaging the Eukaryotic cell membrane Toxemia • Toxins in the bloodstream • Toxigenicity: Capacity of microorganisms to produce toxins.
- 59. Two Types of Toxins 1. Exotoxins • secreted outside the bacterial cell 2. Endotoxins • part of the outer cell wall of Gram (-) bacteria. ??
- 62. I- Exotoxins Mostly seen in Gram (+) Bacteria Most gene that code for exotoxins are located on plasmids or phages
- 63. Three Types of Exotoxins 1. Cytotoxins • kill cells e.g. Diphtheria toxin 2. Neurotoxins • interfere with normal nerve impulses.e.g. Botulinum Toxin 3. Enterotoxins • effect cells lining the G.I. Tract. e.g. Cholera toxin or choleragen.
- 64. Response to Toxins If exposed to exotoxins: antibodies against the toxin (antitoxins) Exotoxins inactivated ( heat, formalin or phenol) no longer cause disease, but stimulate the production of antitoxin • altered exotoxins - Toxoids Toxoids - modified toxin by heat, chemical, radiation, that have lost their toxicity. Injected to stimulate the production of antitoxins and provide immunity.
- 65. Example: DPT Vaccine D - Diphtheria • Corynebacterium diphtheriae P - Pertussis • Bordetello pertussis T - Tetanus • Clostridium tetani DPT - Diphtheria Toxoid Pertussis Antigen Tetanus Toxoid
- 66. Required Immunizations in Jordan 1. Diphtheria 2. Pertussis 3. Tetanus 4. Measles 5. Mumps 6. Rubella • German Measles 7. Polio 9. Hepatitis B Corynebacterium diphtheriae Bordetello pertussis Clostridium tetani Measles virus Mumps virus Rubella virus Polio virus Hepatitis B Virus
- 67. Most genes that code for exotoxins - plasmids or phages Lysogenic convergence Diphtheria Cytotoxin inhibits protein synthesis - resulting in cell death Pseudomembrane • fibrin, dead tissue, bacterial cells
- 68. Lysogenic Convergence Scarlet Fever Streptococcus pyogenes • lysogenic convergence cytotoxin - damages blood capillaries and results in a skin rash • Strep Thoat with a rash
- 69. Rash of Scarlet Fever Caused by Erythrogenic Toxins of Streptococcus pyogenes
- 70. Diseases Caused by Staphylococcal Toxins Scalded Skin Syndrome Toxic Shock Syndrome
- 71. Diseases caused by Neurotoxins Botulism • Clostridium botulinum • Gram (+), anaerobic, spore-forming rod, found in soil • works at the neuromuscular junction • prevents impulse from nerve cell to muscle cell • results in muscle paralysis
- 72. Tetanus (Lock Jaw) Clostridium tetani Gram (+), spore-forming, anaerobic rod neurotoxin acts on nerves, resulting in the inhibition of muscle relaxation tetanospasmin - “spasms” or “Lock Jaw”
- 73. Neonatal Tetanus (Wrinkled brow and risus sardonicus) Source: Color Guide to Infectious Diseases, 1992 Muscle Spasms of Tetanus are Caused by Neurotoxin of Clostridium tetani
- 74. Diseases caused by Enterotoxins Cholera • Vibrio cholerae • Gram (-) comma shaped rods
- 75. Cholera toxin Converts ATP into cAMP causes cells to excrete Cl- ions and inhibits absorption of Na+ ions Electrolyte imbalance H2O leaves by osmosis H2O Loss (Diarrhea) Two polypeptides: A (active) and B (binding). The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes.
- 76. Severe cases, 12 - 20 liters of liquid lost in a day Untreated cases - Mortality Rate about 50% Mortality may be reduced to about 1% • administering fluids and electrolytes
- 77. Rice-water stool of cholera. The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes. Source: Tropical Medicine and Parasitology, 1995 Vibrio Enterotoxin Causes Profuse Watery Diarrhea
- 78. EHEC (Enterohemorrhagic E. coli) E. coli (0157:H7) enterotoxin causes a hemolytic inflammation of the intestines results in bloody diarrhea • Toxin • alters the 60S ribosomal subunit • inhibits Protein Synthesis • Results in cell death • lining of intestine is “shed” • Bloody Diarrhea (Dysentary)
- 79. More on Toxins
- 80. II- Endotoxins • Part of outer membrane surrounding gram-negative bacteria. • Endotoxin is lipid portion of lipopolysaccharides (LPS), called lipid A. • Effect exerted when gram-negative cells die and cell walls undergo lysis, liberating endotoxin. • All produce the same signs and symptoms: • Chills, fever, weakness, general aches, blood clotting and tissue death, shock, and even death. Can also induce miscarriage. • Fever: Pyrogenic response is caused by endotoxins.
- 82. Endotoxin is LPS
- 83. Endotoxins (Continued) • Endotoxins do not promote the formation of effective antibodies. • Organisms that produce endotoxins include: • Salmonella typhi • Proteus spp. • Pseudomonas spp. • Neisseria spp. • Medical equipment that has been sterilized may still contain endotoxins. • Limulus amoebocyte assay (LAL) is a test used to detect tiny amounts of endotoxin.
- 84. Events leading to fever: • Gram-negative bacteria are digested by phagocytes. • LPS is released by digestion in vacuoles, causing macrophages to release interleukin-1 (IL-1). • IL-1 is carried via blood to hypothalamus, which controls body temperature. • IL-1 induces hypothalamus to release prostaglandins, which reset the body’s thermostat to higher temperature.
- 85. Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease
- 86. III. B. The Normal Flora of Humans Types of Symbiosis • Mutualism • A symbiotic relationship in which both species benefit • Commensalism • A symbiotic relationship in which one species benefits, and the other species is neither helped nor harmed
- 87. III. B. The Normal Flora of Humans Types of Symbiosis (cont.) • Parasitism • A symbiotic relationship in which one species benefits, and the other species is harmed • Generally, the species that benefits (the parasite) is much smaller than the species that is harmed (the host)
- 88. III. B. The Normal Flora of Humans Normal flora is present in • skin • upper respiratory tract • oral cavity • intestine, especially large intestine • vaginal tract Very little normal flora in eyes & stomach
- 89. III. B. The Normal Flora of Humans Notably absent in most all internal organs • Absent in: • lower respiratory tract • muscle tissue • blood & tissue fluid • cerebrospinal fluid • peritoneum • pericardium • meninges
- 90. III. B. The Normal Flora of Humans Benefits of the normal flora • Nutrient production/processing eg Vitamin K production by E. coli • Competition with pathogenic microbes • Normal development of the immune system Normal flora and opportunistic infections
- 91. III. C. Generalized Stages of Infection 1. Entry of Pathogen • Portal of Entry 2. Colonization • Usually at the site of entry 3. Incubation Period • Asymptomatic period • Between the initial contact with the microbe and the appearance of the first symptoms
- 92. III. C. Generalized Stages of Infection 4. Prodromal Symptoms • Initial Symptoms 5. Invasive period • Increasing Severity of Symptoms • Fever • Inflammation and Swelling • Tissue Damage • Infection May Spread to Other Sites
- 93. III. C. Generalized Stages of Infection 6. Decline of Infection 5. Convalescence
- 94. Course of Infectious Disease Incubation period is the interval between exposure and illness onset. Convalescence is a time of recuperation and recovery from illness. Depending on various factors an individual may still be infectious during either incubation or convalescence.