Microbial Pathogenesis - Lecture Notes | BIOL 2051, Study notes of Biology

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Chapter 25 Microbial Pathogenesis Host-Pathogen Interactions • Infection = entry of pathogen or parasite • Infection doesn’t always cause disease • Most infections removed by immune system • Primary pathogens (Frank pathogen) • Have ability to penetrate host defenses • Opportunistic pathogens • Cause disease only in compromised hosts • Immune system defective • Break in tissue allows organism access to new site • Loss of other microflora allows organism to bloom • Pathogenicity of organism • Measure of ability to cause disease • Determined by genetic makeup of organism • Infectious dose = ID50 • Number of organisms to colonize 50% of hosts • Virulence • Rate of lethal infections • Lethal dose = LD50 • Number of organisms to kill 50% of hosts Infection Cycle • Spread by direct contact • Spread by indirect contact • Contact with fomites  Inanimate object or substance that can carry infectious microbes o Computer, elevator buttons • Horizontal transmission via vectors • Mosquitoes—Yellow fever, malaria • Reservoir for disease organism • May not show disease symptoms • Mode of entry depends on pathogen • Mucosal surfaces, wounds, insect bites Virulence Factors • Virulence genes • Encode factors allowing pathogen to invade host • Toxins, attachment proteins, capsules • Pathogenicity islands • Section of genome • Contain multiple virulence genes • Often encode related functions • E.g., protein secretion system, toxin production • Transferred as a block from other organisms Virulence Factors  Structures & characteristics of pathogens that allow them to cause disease  Adhesion- ability to adhere to mucus membranes Virulence factors affecting adhesion: • Capsule – outer polysaccharide layer; helps bacteria in attachment; protects them from phagocytosis • Fimbriae/pili – necessary for some organisms to attach (Neisseria & E. coli) • Adhesins – surface proteins bind host cells Invasion & Colonization Invasion: • Pathogens must be able to penetrate the outer layer of skin cells (epithelium) • They can reach inner layers of skin cells through lesions or mucus membranes Colonization: • Once it has invaded a host, it can establish itself and grow Examples of virulence factors affecting invasion & growth • The O & Vi antigens of Salmonella • O – cell surface polysaccharide – prevents phagocytosis • Vi – capsule antigen – prevents complement binding & antibody mediated killing • Blocks ribosome function, cell dies • Forms pseudomembrane over trachea Surviving within the Host Once inside host cell, how to avoid death? • Cell ingests pathogens in phagosome • Some pathogens use hemolysin to break out • Shigella dysenteriae, Listeria monocytogenes • Phagosome fuses with acidic lysosome • Some pathogens secrete proteins to prevent fusion • Salmonella, Chlamydia • Some pathogens mature in acidic environment • Coxiella burnetii—Q fever Viral Pathogenesis Influenza • Influenza virus antigenic drift • RNA Polymerase does not correct replication errors • Frequent mutations in hemagglutinin gene • If mutation allows virus to avoid immune system, virus spreads • New flu vaccine needed every year • Influenza antigenic shift • Two strains infect host at same time • Chicken or swine • Recombined viruses have mix of chromosomes • Immediate alteration of several genes • Cause of 1918 influenza outbreak • Largest single-year loss of life in recorded history HIV • HIV—Avoids host immunity by infecting immune cells • Binds multiple receptors for entry • CD4, chemokine receptor CCR-5 • T cells • Infected cells secrete viral protein • Misregulates other immune system cells Chapter 26 Microbial Diseases Skin and Soft-Tissue Infections Staphylococcus aureus • Boils/ pimples—walled off from body with fibrin • Impetigo- skin infection (common on children and bright red sore on face) • “Scalded skin” syndrome- due to exfoliative toxin (skin pealing off) • Can produce hemolysins, superantigen enterotoxin A (food poisoning), coagulase, leukocidin, superantigen TSST (toxic shock syndrome) • Can also cause pneumonia & meningitis • Treatment with penicillins • MRSA—methicillin-resistant S. aureus • Horizontal gene transfer of drug-resistant genes • Evolved in environment with high levels of antibiotic • Hospitals—nosocomial infections • Resistant to all drugs except vancomycin Streptococcus pyogenes • 60+ strains • Strep throat (pharyngitis) – 5-10% of sore throats • diagnosis- blood agar: slow; antibody test; rapid • infections of the inner ear • impetigo- skin infection • Scarlet fever – exotoxin superantigen; can follow pharyngitis; pink rash & “strawberry tongue” • Rheumatic fever – autoimmune; antibodies against S. pyogenes react with host tissue – damages heart valves • necrotizing fasciitis (“flesh eating”) Many viruses can cause skin rashes • Usually infect through respiratory tract • Chickenpox – caused by Varicella-zoster virus (VZV), a herpesvirus – VZV can lay dormant in nerve cells for long periods of time. Shingles is caused by the migration of VZV to the skin; painful blisters • Measles/rubeola – caused by a paramyxovirus – Symptoms- fever, cough, rash • Mumps- inflammation of salivary glands • Rubella/German measles – Caused by a togavirus – symptoms - similar to measles but milder • Can be prevented with MMR vaccine (all three: measles, mumps, rubella) Many fungal skin infections Respiratory Tract Infections • Most respiratory pathogens are transferred from person to person via respiratory aerosols – coughing, sneezing, talking, breathing • Transmission usually occurs over short distances because microorganisms survive poorly in air • Pathogens that can survive dry conditions such as many Gram + & Mycobacteria are easier to transmit by air Streptococcus pneumoniae- lower respiratory diseases; can also cause meningitis • pneumococcal pneumonia (pneumococcus) • Inflammatory reaction in alveoli (air sacs in lungs) • Usually a secondary infection • Capsule protects organism from phagocytosis • untreated- 30% mortality rate • Alveoli become filled with blood, bacteria, & phagocytic cells • Symptoms = sudden onset of chills, labored breathing, pleural (chest) pain • Pneumonia can also be caused by viruses, other bacteria, or fungi • S. pneumoniae is found in respiratory flora in about 40% of healthy people Corynebacterium diphtheriae • Childhood upper respiratory infection, diphtheria. • Pathogen strains of Corynebacterium diphtheriae produce exotoxin that inhibits protein synthesis • Formation of pseudomembrane – damaged host cells & bacterial cells (can cause hemorrhaging if torn) • Causes constriction of throat, suffocation • Early childhood immunization with diphtheria toxoid (part of DTP) is very effective for prevention of diptheria. Bordetella pertussis • Childhood upper respiratory infection, pertussis. (hooping cough) • Pertussis exotoxin causes tissue damage; endotoxin causes cough • Violent cough that lasts up to 6 weeks • Pathogen binds to ciliated epithelial cells of bronchi and trachea • Early childhood immunization with proteins (acellular pertussis) derived from B. pertussis (part of DTP) is very effective. Mycobacterium tuberculosis (acid-fast) • Tuberculosis • As much as 1/3 world population infected • 11% of deaths due to infectious disease caused by tuberculosis • Tuberculin test for hypersensitivity; acid-fast stain for active infection • Treatment with isoniazid & rifampin – 9 months • Immunization with an attenuated strain of M. bovis (BCG) effectively prevents tuberculosis. • Entero-Hemorrhagic E. coli: EHEC (O157:H7) – O157=serotype of LPS, H7=serotype of flagella Food poisoning • Occurs when food is contaminated with a toxin producing microbe • Toxin causes symptoms which can appear within 1 hour of eating • Most common cause is S. aureus; vomiting & diarrhea (very salt tolerant organism) • Clostridium perfringens causes diarrhea & intestinal cramps • Clostridium botulinum causes botulism, most severe type of food poisoning. Produces neurotoxin; often fatal Most gastroenteritis caused by viruses • Rotaviruses (dsRNA Reovirus) – Highly infectious – Can cause lethal dehydration • Antibiotics ineffective on viruses – kill competing bacteria, allows C. difficile to grow (can occur at low levels) • Causes gastrointestinal disease Protozoal infections • Entamoeba, Cryptosporidium • Giardia lamblia Genitourinary Tract Infections • Urinary tract infections – Many gram negative bacteria grow in urine • Uropathogenic E. coli (UPEC), Klebsiella, Pseudomonas, Enterobacter • Pili – cells adhere against urine stream Sexually Transmitted Infections- • Most sexually transmitted infections are curable or controllable with timely, appropriate medical intervention. • Prevention by abstinence or barriers (condoms). Neisseria gonorrhoeae • Gonorrhea (Gram negative diplococcus) • One of most common human diseases • Enters body through mucous membranes • Infants – eye infections during birth • Female – inflammation of vaginal mucosa, easily unnoticeable, can lead to pelvic inflammatory disease (PID) • Male – painful urethra infection, discharge • Untreated, can result in sterility, damage to heart valves & joints • Prophylactic – erythromycin eye ointment for newborns Treponema pallidum • Syphilis • Newborns can contract it from mother-congenital syphilis • Primary stage • Initial site of infection is usually genitals • lesion called chancre forms • Chancre usually heals but bacteria spread • Secondary stage • Generalized rash • Tertiary stage • infections of skin, bone, CNS • cardiovascular effects, dementia, death • Most of last symptoms due to delayed hypersensitivity reactions Chlamydia trachomatis • Most common STD • 75% of women and 50% of men – no symptoms • If symptoms do occur, they are similar to gonorrhea • Newborns can contract C. trachomatis – conjunctivitis, pneumonia • Nongonococcal urethritis (not caused by N. gonorrhea) • Can cause PID & fallopian tube damage Trichomonas vaginalis • Protozoan responsible for trichomoniasis • Can survive up to 24 hours in urine or semen therefore transmission can occur by contact with fluids (toilet seats, sauna benches) • Symptoms: none in males; vaginal discharge, inflammation of vaginal mucosa, painful urination in females • Diagnosis by microscopic observation of protozoan in discharge. Viruses Human papillomaviruses • Genital warts, cervical cancer • Vaccine (Gardisil) to 4 most virulent viruses available Herpes simplex viruses Herpes simplex virus type 1 • Cold sores/fever blisters • Latent infection; virus persists in nerve tissue Herpes simplex virus type 2 • Painful blisters in genital region • Spread by contact with blisters • Correlation between genital herpes & cervical cancer • Can be transmitted to newborn by mother (C-section advised) • No cure, but blister treatment with oral and topical antiviral drug acyclovir to inhibit viral replication and limit shed of active virus. Human Immunodeficiency Virus (HIV) • Retrovirus that causes AIDS (Acquired Immunodeficiency Syndrome) • one of the most prevalent infectious diseases • HIV destroys the immune system by infecting macrophages & CD4+ T-cells • Opportunistic pathogens kill the immune-compromised host • Worldwide, estimated 33 million people infected, highest percentage in college age women • Highly effective antiretroviral therapy treatment – multiple drugs given at once • First stage—AIDS-related complex – Fever, headache, rash • Second stage—AIDS – Depletion of T cells – Opportunistic infections • Third stage—AIDS-related dementia • Fourth stage—rare cancers – Kaposi’s sarcoma via Herpes virus type 8 infection Central Nervous System Infections West Nile Virus • West Nile fever • Transmitted by mosquito from birds to humans • Symptoms: most inapparent; ~20% fever, headache, nausea, muscle aches, rash, swollen lymph nodes, malaise; <1% encephalitis or meningitis • No effective antiviral drugs for treatment. No human vaccine yet. Prevention by mosquito extermination. Neisseria meningitidis • Bacterial meningococcal meningitis- inflammation of meninges (membranes that line CNS) • Occur in epidemics in closed populations like dorms & military. 30% are carriers. • Initial upper respiratory and blood infections. Meningitis can also occur characterized by sudden onset of rash, headache, vomiting, stiff neck; within hours, coma & death • Vaccination made of polysaccharides from most prevalent strains • Others bacteria and viruses can also cause meningitis Clostridium toxins • C. botulinum—botulinum toxin (“Botox”) – Anaerobe, grows in canned food – Spores survive unless autoclaved – Toxin blocks release of acetylcholine • Prevents muscle movement • C. tetani—tetanus toxin – Anaerobe, grows in puncture wounds • Blood flow interrupted, tissue becomes anaerobic – Toxin blocks release of inhibitory transmitter • Muscles contract uncontrollably, lethal spasms – Immunization with tetanus toxoid vaccination (DTP) is effective for prevention Rabies • Caused by a member of the Rhabdovirus family