1/26/2016 Disease due to microbes is a rare event. Microbes Microbes do not try to cause disease. Microbes are looking for food and defending themselves. Invisible Invaders Amazing Allies Chapter 15 Microbial Mechanisms of Pathogenicity Common How Microorganisms Enter a Host strategies of pathogenicity Learning Objectives A thorough understanding is Identify the principal portals of entry. esesntial to develop Define IDso and LDso better,novel vaccines and Using examples,explain how microbes therapeutic agents adhere to host cells. for treatment and prevention
1/26/2016 1 Invisible Invaders Amazing Allies Chapter 15 Microbial Mechanisms of Pathogenicity • Disease due to microbes is a rare event. • Microbes do not try to cause disease. • Microbes are looking for food and defending themselves. Common strategies of pathogenicity A thorough understanding is esesntial to develop better, novel vaccin n es a d therapeutic agents for treatment and prevention How Microorganisms Enter a Host Learning Objectives Identify the principal portals of entry. Define ID50 and LD50 Using p,p examples, explain how microbes adhere to host cells
1/26/2016 How Microorganisms Enter a Host How Microorganisms Enter a Host Portals of entry Mucous membranes Pathogenicity:the ability to cause disease by overcoming host defenses dedie due to Genitourinary troct-sexually contracted diseases Virulence:the degree of pathogenicity by most microbes Parenteral route Most pathogens have a preferred portal of entry for disease to occur Numbers of Invading Microbes Numbers of Invading Microbes The likelihood of disease increases as the Bacillus anthracis number of pathogens increases. Portal of Entry IDso ID:infectious dose for 50%of a sample Skin 10-50 endospores population Inhalation Measures virulence of a microbe 10.000-20,000 endospores LDso:lethal dose for 50%of a sample Ingestion 250.000-1,000,.000 population endospores Measures potency of a toxin Cutaneous anthrax is easier to acquire than either inhalation or ingestion forms
1/26/2016 2 How Microorganisms Enter a Host Pathogenicity: the ability to cause di b i h t d f disease by overcoming host defenses Virulence: the degree of pathogenicity How Microorganisms Enter a Host Portals of entry Mucous membranes Respiratory tract – easiest and most frequent, inhale into nose or mouth moisture droplets or dust Gastrointestinal tract – food, water, fingers; most die due to stomach acid, bile, enzymes; eliminated in feces Genitourinary tract – sexually contracted diseases Skin (largest organ) Impenetrable by most microbes Accessed by openings, hair follicles, sweat gland ducts Parenteral route Deposited directly into tissues when barriers are penetrated Punctures, bites, injections, cuts, wounds, surgery, skin splits Most pathogens have a preferred portal of entry for disease to occur Numbers of Invading Microbes The likelihood of disease increases as the number of p g atho ens increases. ID50: infectious dose for 50% of a sample population – Measures virulence of a microbe LD50: lethal dose for 50% of a sample population – Measures potency of a toxin Portal of Entry ID Numbers of Invading Microbes Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores Cutaneous anthrax is easier to acquire than either inhalation or ingestion forms
1/26/2016 Adherence Numbers of Invading Microbes Almost all pathogens attach to host tissues at the Toxins portal entry in a process called adherence (adhesion) Portal of Entry LD50 Botulinum 0.03 ng/kg located on the bacterial glycocalyx,fimbriae or pili Shiga toxin 250 ng/kg glycoproteins or lipoproteins Staphylococcal enterotoxin 1350 ng/kg Microbes form biofilms(communities that share much smaller dose of botulinum toxinis neede nutrients)on host tissues as another method of cause symptoms adherence. Infection can be prevented if adherence is blocked- adhesin-receptor interaction is altered. Adhesin (ligand) Electron micrograph showing piliated uropathogenic Escherichia coli(gold) Pathogen tethered to the lumenal surface of a mouse bladder (blue) Surface molecules on a pathogen.called adhesins or ligands.bind specifically to complementary surface receptors on cells of certain host tissues
1/26/2016 3 Numbers of Invading Microbes Toxins Portal of Entry LD50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg Staphylococcal enterotoxin 1350 ng/kg A much smaller dose of botulinum toxin is needed to cause symptoms. Adherence Almost all pathogens attach to host tissues at the portal entry in a process called adherence (adhesion) Adhesins (ligands) on the pathogen bind to receptors on the host cells - located on the bacterial glycocalyx, fimbriae or pili - glycoproteins or lipoproteins Microbes form biofilms (communities that share nutrients) on host tissues as another method of adherence. Infection can be prevented if adherence is blocked – adhesin-receptor interaction is altered. Adhesin (ligand) Pathogen Host cell surface Receptor Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues. Electron micrograph showing piliated uropathogenic Escherichia coli (gold) tethered to the lumenal surface of a mouse bladder (blue)
1/26/2016 Salmonella entering intestinal epithelial cells as a result of ruffling. Flagella cel (c)Bacteria(purple)adhering to human skin e15m How Pathogens Penetrate Host Defenses Most pathogens invade host tissues to cause Learning Objectives disease. Explain how capsules and cell wall components Factors that contribute contribute to pathogenicity. to invasion: Compare the effects of coagulases,kinases, .Capsules hyaluronidase,and collagenase .Cell wall components .Enzymes Define and give an example of antigenic Antigenic variation variation. 一 .Penetration of the Describe how bacteria use the host cell's host cytoskeleton cytoskeleton to enter the cell
1/26/2016 4 Flagella Salmonella entering intestinal epithelial cells as a result of ruffling. Salmonella typhimurium Ruffling of host cell plasma membrane How Pathogens Penetrate Host Defenses Learning Objectives Explain how capsules and cell wall components contribute to pathogenicity. Compare the effects of coagulases, kinases, hyaluronidase, and collagenase. Define and give an example of antigenic variation. Describe how bacteria use the host cell's cytoskeleton to enter the cell. Most pathogens invade host tissues to cause disease. Factors that contribute to invasion: •Capsules •Cell wall components •Enzymes •Antigenic variation • Penetration of the host cytoskeleton
1/26/2016 Capsule Klebsiella pneumoniae Cell Wall Components Glycocalyx around the cell wall o0 M protein ·Increases virulence Streptococcus pyogenes Impairs phagocytosis g found on cell surface and fimbriae Streptococcus pneumoniae- pneumonia mediates attachment to -Haemophilus influenzae-pneumonia epithelial cells and meningitis -helps bacteria resist Bacillus anthracis-anthrax phagocytosis yersinia pestis-plague -Klebsiella pneumoniae -bacterial pneumonia Cell Wall Components Cel‖Wall Components Opa protein Waxy lipid(mycolic acid) -Neisseria gonorrhoeae outer membrane protein -Mycobacterium tuberculosis allows attachment to -resist digestion inside macrophages where the host cell as do it can multiply fimbriae following attachment the host cell takes up the bacteria where it resides
1/26/2016 5 Capsule • Glycocalyx around the cell wall • Increases virulence Klebsiella pneumoniae • Impairs phagocytosis – Streptococcus pneumoniae - pneumonia – Haemophilus influenzae - pneumonia and meningitis – Bacillus anthracis - anthrax – Yersinia pestis - plague – Klebsiella pneumoniae – bacterial pneumonia Cell Wall Components M protein – Streptococcus pyogenes – found on cell surface and fimbriae – mediates attachment to epithelial cells – helps bacteria resist phagocytosis Cell Wall Components Opa protein – Neisseria gonorrhoeae – outer membrane protein – allows attachment to the host cell as do fimbriae – following attachment the host cell takes up the bacteria where it resides Cell Wall Components Waxy lipid (mycolic acid) – Mycobacterium tuberculosis – resist digestion inside macrophages where it can multiply
1/26/2016 Enzymes Coagulase elod fibrinogen is a blood protein produced by the liver converted to fibrin, which forms a clot Staphylococcus aureus forms a fibrin capsule that protects it from the immune system Enzymes Bacterial kinases Break down fibrin Digest the clots formed by the body to isolate the infection Streptococcus pyogenes streptokinase or fibrinolysin,activates plasminogen,which breaks down fibrin clots
1/26/2016 6 Enzymes Coagulase - coagulates (clots) f ngnn ibrinogen in the blood - fibrinogen is a blood protein produced by the liver - converted to fibrin, which forms a clot - Staphl y ococcus aureus forms a fibrin capsule that protects it from the immune system Enzymes Bacterial kinases - Break down fibrin - Di t th l t f d Digest the clots formed by the body to isolate the infection - Streptococcus pyogenes - streptokinase or fib i l i fibrinolysin, ti t activates plasminogen, which breaks down fibrin clots
1/26/2016 Enzymes Enzymes Collagenase Hyaluronidase -produced by Clostridium digests haluronic acid, a type of prorein mar fonmgen polysaccharide that connective tissue of muscles holds cells together -helps spread the infection -Streptococci IgA protease -tissue blackening of infected wounds 0 helps bacteria spread IgA antibodies block from initial infection bacteria to site Neissseria gonorrhoeae Antigenic Variation Infection induces production of me n eeonof antibodies that recognize a pathogen inactivatet Antigens are often surface-located Pathogens have antigens on their outer surface. molecules such as antigens and antibodies protein. 器 If a microbe changes its sur les often,then the eourmemrre re production of antibodies is always Many bacteria are capable of antigenic variation behind and it can evade the immune system
1/26/2016 7 Enzymes Hyaluronidase - digests haluronic acid, a type of polysaccharide that holds cells together - Streptococci - tissue blackening of infected wounds - helps bacteria spread from initial infection site Enzymes Collagenase - produced by Clostridium - breaks down collagen, a protein that forms connective tissue of muscles - helps spread the infection IgA protease - destroys IgA antibodies that bind bacteria - IgA antibodies block adherence of bacteria to host tissues - Neissseria gonorrhoeae Antigenic Variation Adaptive immunity: specific defensive response of the body to an infection or to antigens. In the presence of antigens, the body produces antib di o es, hi h bi d th ti d d t which bind th e antigen and destroy or inactivate it. Pathogens have antigens on their outer surface. Pathogens alter their surface antigens and antibodies are thus ineffective. At the start of an infection, an immune response st t b t ti i i ti t it f tarts but antigenic variation prevents it from being useful. Neisseria gonorrhoeae has several copies of the gene encoding the Opa outer membrane protein. Many bacteria are capable of antigenic variation. Infection induces production of antibodies that recognize a pathogen Anti ens are often Antigens are often surface-located molecules such as protein. If a microbe changes its su f c m l cul s its surface molecules often, then the production of antibodies is always behind and it can evade the immune system
1/26/2016 Penetration into the Host Cell Cytoskeleton-the Cytoskeleton movers and shapers in the cell Invasins Animal cell with c -Surface proteins produced by bacteria that (gre actin filaments(red),and the rearrange actin filaments of the cytoskeleton nucleus (blue). Cause membrane ruffling Salmonella strains and Escherichia coli Some pathogens use actin to move from one cell to the next Shigella and Listeria as a re ce Motorized tail of actin moving the bacteria in the cell. Listeria species and Shigella Membrane ruffling is the result of disruptionm species uses actin tails to of the cytoskeleton of the host cell. penetrate neighboring cells
1/26/2016 8 Penetration into the Host Cell Cytoskeleton Invasins – Surface proteins produced by bacteria that rearrange actin filaments of the cytoskeleton • Cause membrane ruffling • Salmonella strains and Escherichia coli S th ti t f ll Some pathogens use actin to move from one cell to the next – Shigella and Listeria Animal cell with cytoskeleton stained microtubules (green) Cytoskeleton – the movers and shapers in the cell stained microtubules (green), actin filaments (red), and the nucleus (blue). Salmonella entering intestinal epithelial cells as a result of ruffling. Flagella Salmonella typhimurium Ruffling of host cell plasma membrane Membrane ruffling is the result of disruption of the cytoskeleton of the host cell. Motorized tail of actin moving th b t i i th ll the bacteria in the cell. Listeria species and Shigella species uses actin tails to penetrate neighboring cells
1/26/2016 How Bacterial Pathogens Damage Host Common strategies Cells of pathogenicity Learning Objectives If apathogen ove rcomes the Describe the function of siderophores. host defense.then the microbe can cause damage rend effeet o Using the host's nutrients 。 Causing direct damage at the site of infection Define the mechanisms of action of A-B Producing toxins that are toxins,membrane-disrupting toxins, transported to sites superantigens,and genotoxins. distant to the infection Describe the roles of plasmids and lysogeny in Inducing hypersensitivity pathogenicity. reactions Using the Host's Nutrients: Structure of enterobactin,a Siderophores type of bacterial siderophore =0 Iron is required for most pathogenic An example of iron transport across bacteria The membrane (CO-CH-CH2-0) Concentration of free iron in the body is low since most iron is bound to iron- transport proteins,such as lactoferrin, transferrin,and hemoglobin. Siderophores are proteins secreted by pathogens that bind iron more tightly than host cells
1/26/2016 9 How Bacterial Pathogens Damage Host Cells Learning Objectives • Describe the function of siderophores. • Provide an example of direct damage, and compare this to toxin production. • Contrast the nature and effects of exotoxins and endotoxins. • Define the mechanisms of action of A-B toxins, membrane-disrupting toxins, superantigens, and genotoxins. • Describe the roles of plasmids and lysogeny in pathogenicity. Common strategies of pathogenicity If a pathogen overcomes the host defense, then the microbe can cause damage • Using the host’s nutrients • Causing direct damage at the site of infection • Producing toxins that are transported to sites distant to the infection • Inducing hypersensitivity reactions Using the Host's Nutrients: Siderophores • Iron is required for most pathogenic bacteria • Concentration of free iron in the body is low since most iron is bound to irontransport proteins, such as lactoferrin, transferrin, and hemoglobin. • Siderophores are proteins secreted by pathogens that bind iron more tightly than host cells. Structure of enterobactin, a type of bacterial siderophore. An example of iron transport across the membrane. - Complex is transported - Only just the iron is transported
1/26/2016 Direct Damage Production of Toxins Disrupts host cell function Toxins:poisonous substances produced by Uses host cell nutrients microorganisms Produces waste products -Produce fever,cardiovascular problems. Multiplies in host cells and causes rupture diarrhea,and shock Toxigenicity:ability of a microorganism to produce a toxin Toxemia:presence of toxin in the host's blood esembles progresses to se Intoxications:presence of toxin without microbial growth Trarsmitted from birds. Production of Toxins exotoxins Toxins are of two general types base on their position in the microbial cell 尝二等 1-Exotoxin into the surrounding medium during log 2-Endotoxin Bacterial toxins cause damage to host cells. fever,cardiovascular disturbance,diarrhea, and shock produces .inhibit protein synthesis,destroy blood cells and vessels,disrupt the nervous system causing spasms elicit inflammatory responses Exotaxins de the c目 o
1/26/2016 10 Direct Damage • Disrupts host cell function • Uses host cell nutrients • Produces waste products • Multiplies in host cells and causes rupture Example: Chlamydophila psittaci The bacterium can be inhaled or ingested by humans and cause psittacosis, an infection that resembles the flu and progresses to a severe pneumonia. Transmitted from birds. Production of Toxins Toxins: poisonous substances produced by microorganisms – Produce fever cardio Produce fever, cardiovascular problems vascular problems , diarrhea, and shock Toxigenicity: ability of a microorganism to produce a toxin Toxemia: presence of toxin in the host's blood Intoxications: presence of toxin without microbial growth Production of Toxins Toxins are of two general types base on their position in the microbial cell 1 - Exotoxin 2 - Endotoxin Bacterial toxins cause damage to host cells. • fever, cardiovascular disturbance, diarrhea, and shock • inhibit protein synthesis, destroy blood cells and vessels, disrupt the nervous system causing spasms • elicit inflammatory responses Proteins produced inside pathogenic bacteria, most commonly gram-positive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase. Cell wall Clostridium botulinum, an example of a grampositive bacterium Exotoxins: toxic substances released outside the cell that produces exotoxins