This action might not be possible to undo. Are you sure you want to continue?
Kunle Kassim, PhD, MPH Professor, Microbiology August, 2010
It is important for you to review the lecture powerpoint on Host/Bacteria Interactions from first yearbefore coming to class for this lecture.
• • • • • • • • • Review the diversity and significance of bacterial flora in the maintenance of immunity Review the various types of flora distruption and health consequences to the host. Review determinants of pathogenicity Discuss the roles of endotoxin and exotoxins in specific instances of bacterial pathogenesis Illustrate invasiveness and dissemination of bacterial pathogenesis with Salmonella and Shigella pathogenesis. Discuss the different ways that bacterial pathogens exert damage and injury to the host, using cystic fibrosis, lyme disease and bacterial urethritis as illustrations Present the different types of host defenses, including the constitutive elements of innate and adaptive immunity, humoral and cellular immunity, inflammatory and acute phase responses. Describe the emerging patterns and serious significance of nosocomial infections Discuss the nature, usefulness and schedule of bacterial vaccines, particularly in preventing childhood infectious diseases.
Normal Bacterial Flora Bacterial Virulence Factors Mechanisms of Pathogenicity
Host Defense Mechanisms Selected Bacterial Diseases
(Review lecture materials on Bacteria/Host Intreactions)
gun violence • Flora displacement/contamination . bacterial vaginosis • Excessive antibiotic use .vaginal candidaisis.Distruption of Normal Flora • Trauma . pseudomembranous colitis by Clostridium difficile .appendix rupture. dental extraction.UTI. auto accidents.
coli infections .Distruption of Normal Flora • UTI – – – – Tumors Bladder incontinence Ureteric reflux Poor hygiene – E.
Determinants of Pathogenicity • • • • • • • • • • • • • Ports of entry Modes of transmission Bacterial adherence Invasiveness/Dissemination Pathological damage Endotoxin / Exotoxins Fever / Disease onset Host defenses Evasion of host defenses Siderophore production Plasmids Bacterial vaccines (Review last year’s lecture materials on Bacteria/Host Interactions) .
with a fatality rate of 25-50 percent in USA • Exotoxins -most are polypeptides.Toxins • Endotoxin (Lipid A component of LPS) -Unlike exotoxins. are antigenic and can be converted to toxoids . responsible for gram negative septicemia. lipid A is not antigenic and cannot be converted to a toxoid.
Endotoxin and Septicemia • Fever • Activation of coagulation process • Depression of RES • Vascular collapse .
followed by shock • Lipid A may inhibit macrophages from degrading fibrin polymers trapped in blood vessels . causing intravascular coagulation.Lipid A. Coagulation and RES • Lipid A activates clotting mechanism. with formation of fibrin • Fibrin may clog small blood vessels.
followed by shock. which causes increased vascular permeability and dilatation • This causes low blood pressure (hypotension). multiple organ failure and death . liver. brain). impairs blood flow to vital organs (kidneys. lung.Lipid A and Vascular Collapse • Lipid A activates macrophages to release TNF-α.
Neisseria species • • • • • • Are all gram negative cocci Oxidase. catalase positive Multiply intracellularly Neisseria meningitidis Neisseria gonorrhea Neisseria sicca .
pneumonia.Neisseria meningitidis • • • • • Gram negative diplococci Infection from aerosol transmission in close contacts Polysacharide capsule is antiphagocytic LPS. capsule and sIgA protease are major virulence factors Meningitis. fever. meningococcemia with hemorrhagic lesions are major clinical manifestations • Prevented by immunization with polysacharide-protein conjugate vaccine .
Death from Neisseria septicemia and meningitis .
Neisseria urethritis • Gonorrhea with purulent discharge • Disseminated infections via blood to skin. joints • Ophthalmia neonatorium (acquired eye infection) .
Complications of Gonococcal Infection • Skin lesion • Septic arthritis • Ophthalmia neonatorium .
Neisseria gonococcus / Chlamydia Urethritis Differentiation .
Bacterial Classification and Pathogenesis .
N. meningitidis) . influenzae.Meningitis (Strep pneumo. H.
Exotoxins • Enzymatic lysis alpha toxin—Clostridium perfringes • Pore formation alpha toxin—Staph aureus • Protein synthesis inhibition diphtheria & shigella toxins • Nerve-muscle transmission-inhibition tetanus toxin-spastic paralysis botulinum toxin-flaccid paralysis .
Modes of Action of Selected Exotoxins .
Cholera (Vibrio cholerae) .
C.Clostridium and Bacillus • Identification of species based on spore location and oxygen metabolism: . anthracis . botulinum .C. tetanus .B. perfringes . difficile .C.B. cereus .C.
Spore Location for Species ID .
Tetanus (Clostridium tetani and skeletal muscle flexion) .
Bacillus anthracis (potential bioterrorism agent. 2001) .
Gram Stain of B. anthracis in Lung Exudate of an Anthrax Patient .
Bacterial Classification and Pathogenesis .
Staphylococcus and Streptococcus • Tetrad cocci of Staph aureus • (MRSA) • String-like cocci of Strep pneomoniae/ Strep viridans • Enterococcus faecalis • MDR-Strep/Entero .
protein A. among athletes) . exfoliative toxin.Staphylococcus aureus Diseases • Toxin-mediated food poisoning. toxic shock syndrome. serious problem in hospitals. wound infections. cytotoxins/hemolysins. folliculitis. septic arthritis Virulence Factors • Capsule. coagulase/catalase/beta-lactamase enzymes • Methycillin-resistant Staph aureus (MRSA) (antibiotic resistant strain. cutaneous impetigo. enterotoxins. in the US military. osteomyelitis. pneumonia.
Scalded skin syndrome due to Staphylococcus aureus exotoxin .
Gram Stain of Strep viridans in exudate of cardiac valves .
Bacterial endocarditis from a dental extraction • .
pyelonephritis. LPS. shiga toxins. neonatal meningitis. R-plasmid . coli Pathogenesis Diseases • Gastroenteritis.E. intraabdominal infections Virulence Factors • Capsule. bacteremia. cystitis. aerobactin). UTI. hemolysins. siderophores (enterobactin.
Invasiveness / Dissemination • Exotoxins and Extracellular enzymes Extracellular enzymes – – – – – – _ Hyaluronidase dissolves connective tissue Collagenase hydrolyses muscle connective tissue Streptokinase lyses blood clots Phospholipases damage cell membranes Lecithinase damages cell membranes Staphylokinase (fibrinolysin) dissolves fibrin clots Hemolysins lyse erythrocytes and white blood cells .
dysentery • Low infective dose (100 cells) • Salmonella • Invades w invasion proteins • Replicates in acidic host cell vacuole • Replicates and transported by macrophages in blood circulation • Invades other systemic organs. but not deeper GI tissues • Causes diarrhea. enteric fever • High infective dose (>I million cells) .C.D) • Replicates in host cell cytoplasm • Induces apoptosis of phagocytes • Produces cytotoxin (60s ribosome protein inhibitor) • Invades deeper tissues.Shigella/Salmonella Invasive & Dissemination Mechanisms • Shigella • Invades M cells w 4 invasion proteins (IpaA. but not blood circulation • Causes diarrhea.B.
Salmonella/Shigella Invasive & Mechanisms .
abnormal sweat electrolyte concentrations.Cystic Fibrosis • Genetically inherited disorder occurring in 1 of 2500 live Caucasian births • Caused by pancreatic insufficiency. influenzae. H. Pseudomonas aeruginosa –most virulent and antibiotic resistant) and pneumonia . viscid bronchial secretions • Bronchial secretions lead to stasis in lungs and disposition to infections ( Staph aureus.
Cystic Fibrosis .
• Caused by Borrelia burgdorferi • Transmitted by hard ticks (Ixodes species) • Human infections most prevalent in summer months in Europe and USA • Accompanied by fever, headache, myalgia, lymphadenopathy, skin lesions (erythema chronicum migrans) • Neurological complications (meningitis, encephalitis, peripheral neuropathy) • Cardiological (heart block, myopericarditis) • Arthralgia, arthritis (immune complex mediated) • Treatable with penicillin or tetracycline at early stage
Lyme Disease (rash of erythema chronicum/ inflammation)
Host Defenses • • • • • • • • Barriers to Infection Innate and adaptive immunity Humoral and cellular immunity Phagocytosis Complement activation Inflammation Acute phase response Hypersensitivity Reactions .
Barriers to Infection .
Innate and Adaptive Immunity .
Antibody Responses to Infections .
Various Roles of Macrophages .
Macrophage and Neutrophil .
Host immune responses to bacterial infections .
Cytokine and Antibody Networks in Bacterial Infections .
TNF-α) to induce acute-phase response • May be accompanied by antigen neutralization and cytotoxicity . eosinophils) and endogenous mediators (complement. basophils.Inflammation • Consequence of a microbial infection • Recruitment of inflammatory cells (neutrophils. prostaglandin E2) to sites of infection • Production of inflammatory cytokines ( IL-1. IL-6. macrophages.
Stages of Inflammation • • • • • Tissue Damage Vasodilation Exudation Endothelial adherence Diapedes (phagocyte migration) • Tissue repair .
Inflammation from Lyme Disease (rash of erythema chronicum) .
Induction of acute phase proteins in response to an infection .
phagocytosis) against infection. but excessive production during sepsis by LPS can lead to shock • What are other acute phase responses??? . prostaglandin E2. TNF-α.Acute Phase Response • Also a response to infection as with inflammation • Triggered by IL-1. coagulation proteins) • Reinforce innate defenses (complement activation. interferon • Induce production of acute phase proteins (C-reactive protein. complement components. inflammation. IL-6.
Hypersensitivity Reactions to Bacterial Infections .
.Antigenic Variation • Periodic changes of surface antigens by the organism allows it to bypass and not be affected by the host immune responses. Lyme disease and trypanosomiasis. This occurs in HIV infection.
Stages of a Disease .
Hospital-acquired (Nosocomial) Infections .
Pennsylvania 2004 Nosocomial Infections .
Sites of Antibiotic Activities .
exposure to vaccines • Live vaccine – attenuated Mycobacterium bovis • Inactivated toxoid – tetanus vaccine • Inactivated killed – typhoid vaccine • Subunit capsular polysacharides (poor immunogens) -Hemophilus influenzae b.natural exposure to microbes . Streptococcus pneumoniae Salmonella typhi • Conjugate vaccines – polysacharide units conjugated to protein molecules .Immunization • Passive – maternal antibodies thr’ placenta and mother’s milk • Active -. Neisseria meningitidis.
Childhood Immunization Schedule .
Case Studies .
Mr. Laboratory cultures yielded 3 x 105 colonies of Escherichia coli per ml of urine. Within 2 days. . some pain. Hamilton developed a urinary tract infection with low-grade fever. Hamilton developed bacteremia with hypotension and shock. His doctor eventually controlled his bacteremia with gentamycin therapy. a 69-year old man. The organisms were resistant to all tested antibiotics except for aminoglycosides. Hamilton. Mr. the surgeons placed a Foley catheter into his bladder. Three days later. Because of concern about postoperative bleeding during urination.CASE 1: URINARY TRACT INFECTION Mr. underwent a transurethral prostatectomy for cancer of the prostate. and pyuria.
What other organism could have been isolated from his infection site? Give reasons for your choice of organism. List three characteristics of aminoglycosides and their modes of action.Questions (#1) • I. What bacterial component induced his fever. hypotension and shock and how? • 3. . What was the source of Mr. Hamilton's infection? • 2. • 4.
Wilson. When she returned to see the surgeon I month later. She continued to have pain but did not tell her family. She was treated intravenously with vancomycin for 6 weeks and her wound was debrided. Her postoperative course was complicated by bleeding in the mediastinum. After 2 more months of hospitalization. Ms. she reported her pain and low-grade fever. which required more surgery . Ms. Cultures of the pus yielded Staphylococcus epidermidis. Three weeks later. with the wires in her sternum removed. she was discharged and continued her convalescence at home. underwent a mitral valve replacement along with surgery for a coronary artery bypass graft. noticed some purulent drainage along the wound site on her chest. At the end of this period. an 85-year-old woman with rheumatic heart disease.She did well after these operations and was discharged after 12 days.CASE 2: NOSOCOMIAL WOUND INFECTION Ms. Wilson. she required a plastic surgical procedure and a muscle flap to close the wound. Probing the wound. assuming that the pain was related to her healing process. The surgeon noted that there was considerable drainage at the wound site. Wilson was hospitalized again for radical debridement (cleaning) of her chest wound. he noticed a lot of pus. .
In the absence of vancomycin. .. Wilson's wound infection? • 4. What was the source of her postoperative wound infection? • 3 . • 2. Describe the bacterial pathogenesis of rheumatic heart disease.What is the mode of action of vancomycin and why was it the drug of choice for Mrs. what other antibiotic(s) would you choose to clinically manage the wound infection? Describe its mode of action. including the organisms that may be associated with its causation.Questions (#2) I.
free periods. but then subsided. During the second year of illness. Blood analysis reveled a high titer of IgM antibodies against a Gram negative spirochete. but the IgG response was negative. and his antibody response was high for IgG and low for IgM. The swelling of the knees remained for about one year. neck stiffness and photophobia. 36-year-old male resident of New Jersey. the patient had a sudden onset of severe swelling of one knee and then the other. A week later. developed joint and muscle pains and an expanding erythematous skin lesion on his left leg shortly after his summer vacation. Mr . Ten months after the resolution of the initial symptoms. Synovial fluid analysis revealed numerous white cells.Case # 4 Simo da Silva.da Silva had severe neuritic pain on the skin of his abdomen within the distribution of the T8 through T 11 dermatomes. which occurred in one joint at a time for several days. he started experiencing severe headache. His immunogenic profile showed that he had Ill-A-DR4 and Ill-A-DR+ specificities. . followed by longer pain. This symptom was followed by intermittent joint pains. He also noticed multiple secondary annular skin lesions three weeks later.
How did Mr. What does his immunologic profile ofHLA-DRA4 and HLA-DR2 specificities mean? . What antibiotics would you use to treat his initial and late diseases? Is this a case of acute or chronic infection or disease? • 3. What type of white cells ( T cells.Questions (#4) • I. • 5. basophils. da Silva acquire the spirochete infection and what is your identification of the organism? • 2.da Silva late disease stage. What bacterial and immune factors are responsible for his intermittent joint pains and knee swelling? • 4. B cells. neutrophils. macrophages ) were found in the synovial fluid? • 6. Explain the initial high IgM and no IgG titers in the early stage of the disease and the low IgM and high IgG titers in Mr .
Case #5 Three young males were brought to Howard University Hospital Emergency Clinic over the course of two days. One of the bacterial isolates was identified as Streptococcus pneumoniae. white blood cell (wbc) counts of over 15. mostly neutrophils. They were all lethargic with fevers of 101 to 104o F. . but their cerebrospinal fluid (csf) cultures yielded three different organisms. They were diagnosed with bacterial meningitis. the second as Hemophilus influenzae tybe b and the third as Neisseria meninigitidis.000 cells/μl.
• What are the epidemiological characteristics of the meningitis caused by each organism? • What antibiotics of choice would you use to treat the patients? Give reasons for your choice. • What are the modes of action for your choice of antibiotics? • What types of resistance mechanism may be used by each of the organisms to inhibit the activity of your selected antibiotics? .Questions (#5) • What bacterial culture chracteristics and laboratory methods were used to separately identify the three organisms? • What is the pathogenic bacterial structure that is common to the three organisms and how is its composition different for each organism? • Describe the pathway(s) that were taken by the organisms to get into the patients’ csf.
Meningitis 4. lmpetigo 11. Conjunctivitis 7.Home-Work Exercise • • • • • • • • • • • • • List organisms that may be associated with the following conditions 1. Pharyngitis 5. Cellulitis 12. Gastroenteritis 9. lntra-abdominal abscess 8. Urinary Tract infections 10. Pneumonia 6. Sepsis . Endocarditis 3. Bacteremia 2.
Mosby.. Mosby. et al. et al. Inc. 3rd edition by Moselio Schaechter. 47 in Medical Microbiology.. 1998. . 2004. 6th edition by Patrick Murray et al. William & Wilkins. Inc.Reading References • Chapters 9-13. 3rd edition by Cedric Mims. 7. • Chapters 6. 2009 • Chapters 8 -10 in Medical Microbiology. 8 and 9 in Mechanisms of Microbial Diseases. 18 .
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.