Microbiology: Basic and Clinical Principles PDF

Microbiology: Basic and Clinical Principles Second Edition Chapter 10 Host–Microbe Interactions and Pathogenesis Presented by...

Microbiology: Basic and Clinical Principles Second Edition Chapter 10 Host–Microbe Interactions and Pathogenesis Presented by Janet Dowding, Ph.D. St. Petersburg College Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Case Copyright © 2023 Pearson Education, Inc. All Rights Reserved Basics of Host–Microbe Interactions After reading this section, you should be able to: Describe host–microbe interactions and discuss how they can foster health or lead to disease. Discuss how shifts in normal microbiota levels or location may promote disease. Discuss why a commensal organism in one host could be a pathogen in another host. Explain what tropism is and discuss how it can influence pathogen emergence. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (1 of 8) Host–microbe interactions are a dynamic give-and-take Normal microbiota colonize our skin, areas of the digestive, genital, urinary, and respiratory systems Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (2 of 8) In return for a place to live, some of our microbiota... – Manufacture vitamins for us – Compete with potential pathogens – Promote immune system maturation These microbes have mutualistic relations with us Disrupting normal microbiota balance can compromise a patient’s health Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (3 of 8) Pathogens: disease-causing microbes Pathogen have adaptations that allow them to interact with certain host tissues – Dangerous to the host Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (4 of 8) Dysbiosis: microbiota disruption Examples: – Course of antibiotics kills off normal microbiota in the gut – Allows Clostridioides difficile (usually present in small numbers in the intestines) to suddenly flourish and cause disease Copyright © 2023 Pearson Education, Inc. All Rights Reserved  Normal microbiota Host–Microbe Interactions Are Not Always Harmful (5 of 8) Microbiota balance Patient with normal gut microbiota is admitted to healthcare facility for an infection that does not have intestinal involvement––perhaps bacterial pneumonia Antibiotic therapy Patient’s normal microbiota is disrupted by an antibiotic treatment for their bacterial pneumonia C. difficile exposure Patient exposed to C. difficile via fomites or healthcare workers’ hands Dysbiosis Microbiota imbalance Due to limited competition, C. difficile readily flourishes in the large intestine of the patient who underwent antibiotic treatment Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (6 of 8) Due to differences in host factors, a harmless species of the normal microbiota in one host may be pathogenic in another For example: – Group B streptococci (GB S) infections = – 30% of women harbor GBS as normal commensals in the vagina – Associated with sepsis, meningitis, and pneumonia in newborns – Pregnant women are screened for GBS Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (7 of 8) The immune system recognizes our normal microbiota’s presence – Mounts a moderate response to it – Normally a balanced communication between our immune system and resident microbes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Are Not Always Harmful (8 of 8) Opportunistic pathogens are agents of disease under certain circumstances Examples: – Escherichia coli in the appendix enters the abdominal cavity – Weakened immune system allows yeast infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tropism Is the Preference of a Pathogen for a Specific Host (1 of 2) All microbes typically require specific host features to establish infection Tropism: preference of a pathogen for a specific host (and even a specific tissue within the host) Most microbes exhibit some level of tropism, but this factor can change over time Most emerging pathogens expanded host or tissue range to become able to infect humans Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tropism Is the Preference of a Pathogen for a Specific Host (2 of 2) Even when a pathogen successfully invades its preferred host and makes its way to its favored tissue, that doesn’t necessarily mean it will cause disease Many host factors, from age and gender to overall health and life habits, impact whether disease develops Copyright © 2023 Pearson Education, Inc. All Rights Reserved Introduction to Virulence (1 of 2) After reading this section, you should be able to: Define pathogenicity and virulence. Describe various virulence factors and provide examples of how host–microbe interactions impact pathogen virulence and transmission. Discuss what R0 and Re values reveal, and state when these values may be useful in epidemic management. Explain why virulence is best viewed as an evolving property. Define the term attenuated pathogen. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Introduction to Virulence (2 of 2) After reading this section, you should be able to: Distinguish between ID50 and LD5050. Compare and contrast endotoxins and exotoxins and explain how endotoxins can contribute to septic shock. Describe and give examples of the three main types of exotoxins. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Influence Virulence (1 of 3) Pathogenicity: ability of a microbe to cause disease Virulence: describes the degree or extent of disease that a pathogen causes Virulence factors: mechanisms pathogens overcome our defenses (e.g., features that help microbes adhere to host cells, invade host tissues, etc.) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Influence Virulence (2 of 3) TOXINS IMMUNE SYSTEM EVASION LPS in Diverse Gram-negative secreted Diverse Various Capsule cell wall toxins enzymes toxins Fimbriae Pathogen ADHESION Flagella Binding factors Pili Various toxins Diverse Iron-binding Enzymes (kinases, enzymes proteins coagulases, etc.) NUTRIENT INVASION ACQUISITION Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host–Microbe Interactions Influence Virulence (3 of 3) Making virulence factors requires an energy investment, so a pathogen only develops and keeps virulence factors that bestow a benefit Pathogens develop new virulence factors in response to the host and selective pressures Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host Factors and Virulence (1 of 2) Virulence is also associated with host properties (e.g., immune fitness, normal microbiota balance) Virulence factors damage host cells by: – Directly damaging host cells – Provoking dangerous immune responses Copyright © 2023 Pearson Education, Inc. All Rights Reserved Host Factors and Virulence (2 of 2) Examples: Influenza pandemic of 1918 – More virulent in young adults than in older patients In typical flu outbreaks the elderly suffer higher mortality rates SARS-CoV-2 infections are more likely to be asymptomatic in children Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission and Virulence (1 of 2) Virulence factors are often linked to transmission If you learn how a pathogen is transmitted, you can often deduce the pathogen’s virulence factors Pathogens that are more easily transmitted from one host to a new host become more prevalent in populations Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission and Virulence (2 of 2) A pathogen’s basic reproduction number, or R0 (R-naught) value, is a measure of a pathogen’s transmissibility, or contagiousness – if R00 is 2.0, then one infected person is expected to infect an average of two other people in a fully susceptible population More appropriate to consider in the midst of epidemics and pandemics is a pathogen’s effective reproduction number, or Re – Re values can change as host-pathogen interactions change Copyright © 2023 Pearson Education, Inc. All Rights Reserved A Pathogen’s Environment Influences Virulence (1 of 2) A pathogen’s virulence is best viewed as an evolving property because it changes in response to host factors as well as environmental factors Pathogens evolve new virulence factors – Through interacting with their environment – Responding to the selective pressures Copyright © 2023 Pearson Education, Inc. All Rights Reserved A Pathogen’s Environment Influences Virulence (2 of 2) Attenuated: pathogen is still infectious, but weakened Pathogens often become attenuated when grown in cell culture – Lose virulence factors needed to cause disease – Still infectious but weakened – Do not cause disease in an immunocompetent host – Sometimes used in vaccines Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Dosage of Pathogen and Toxin Exposure Affects Host Health Outcomes (1 of 3) For a pathogen to establish disease it must first infect the host Infectious dose-50 ID50 – Number of cells or virions needed to establish an infection in 50% of exposed hosts – More infectious pathogens have a lower ID50 Just because a pathogen is highly infectious doesn’t mean it is especially dangerous Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Dosage of Pathogen and Toxin Exposure Affects Host Health Outcomes (2 of 3) Lethal dose-50 (LD50) – Amount of toxin needed to kill 50% of affected hosts that are not treated Table 10.1 Examples of Infectious Dose and Lethal Dose Agent Disease ID50 I D sub 50 LD50 50 L D sub 50 Bacillus Anthrax Cutaneous anthrax: 10–50 8.4 g/kg body weight (for 8.4 micrograms per kilogram anthracis bacterial spores Respiratory B. anthracis lethal toxin anthrax: 10,000–20,000 spores in canines) Gastrointestinal anthrax: 250,000–1 million spores Botulinum Botulism Not applicable 0.001  g /kg body weight 0.001 micrograms per kilogram toxin A (neurotoxicity; (Toxins do not have an (injected or oral) toxin from ID50 0.07  g /kg I D sub 50 0.07 micrograms per kilogram because although they are 50 often body weight (inhaled) Clostridium botulinum) made by infectious agents, they (Based on studies in are not themselves infectious.) nonhuman primates) Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Dosage of Pathogen and Toxin Exposure Affects Host Health Outcomes (3 of 3) ID50 and LD50 can change based on: – Species affected – Host’s immune fitness – Route of exposure Note: LD50 and ID50 measures usually come from animal studies, so they are not a perfect predictor of what would occur in people Copyright © 2023 Pearson Education, Inc. All Rights Reserved Toxins are Major Virulence Factors (1 of 2) Toxins: molecules that generate a range of adverse host effects such as tissue damage and suppressed immune response Toxigenic: microbes that make toxins Toxemia: toxins in the bloodstream Two classes of toxins: – Endotoxins – Exotoxins Copyright © 2023 Pearson Education, Inc. All Rights Reserved Toxins are Major Virulence Factors (2 of 2) Table 10.2 Comparing Endotoxins and Exotoxins Properties Endotoxins Exotoxins Made of Lipid Protein Made by Gram-negative bacteria Gram-negative and Gram-positive bacteria Released from Gram-negative cell wall when Actively growing bacteria bacteria divide or die Vaccines No Yes (some) Fever Yes Sometimes (certain superantigens Can be neutralized No Yes (some) in patient Toxicity level Lower (relatively high LD50 ) LD50 Higher (many have a low LD50) LD Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (1 of 6) Gram-negative bacteria have an outer membrane rich in lipopolysaccharide (LPS) LPS consists of: – Lipid portion (Lipid A) – Sugars Lipid A region of LPS is called endotoxin – Toxic to us and other animals Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (2 of 6) Mainly released when Gram-negative bacteria die LPS Endotoxin Gram-negative bacterium Lipid A (endotoxin) is a Endotoxin is released when component of LPS in the cell wall breaks apart outer membrane of cell wall. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (3 of 6) The immune system and/or antibiotics kill Gram-negative pathogens, which causes… – Increases in circulating endotoxin levels – Leads symptoms to including fever, chills, body aches, hypotension, tachycardia, increased respiratory rate, inflammation, a feeling of disorientation, nausea, and vomiting Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (4 of 6) If present in sufficient quantities, endotoxin causes septic shock – May kill the host as organs fail – Septic shock kills 11 million people per year globally Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (5 of 6) Endotoxemia: endotoxin in the bloodstream Endotoxins enter from… – Localized infections – Systemic infections – Gram-negative microbiota are introduced to areas where they don’t belong – Surgery complications Copyright © 2023 Pearson Education, Inc. All Rights Reserved Endotoxins (6 of 6) Treating lipid-based endotoxins… – Not readily neutralized – No vaccines to protect against them Necessary to ensure that endotoxins don’t contaminate anything used in patient care (e.g., drugs, implanted devices, etc.) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (1 of 9) Exotoxins – Toxic – Soluble proteins – Affect a wide range of cells – Made by both Gram-positive and Gram-negative bacteria Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (2 of 9) Exotoxins are named based on the organism that makes it or the type of cells it targets – Neurotoxins—affect the nervous system – Enterotoxins—target the GI tract – Hepatotoxins—affect the liver – Nephrotoxins—damage the kidneys To date, >200 exotoxins have been described Exotoxins are often classified into three main families based on their mode of action Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (3 of 9) Type I exotoxins – Membrane-acting extracellular toxins – Bind to target via receptors on the surface – Propagate a signaling cascade via the receptor – Evokes changes in gene expression of host – Leads to diverse outcomes ▪ Range from temporarily altered cell physiology to cell death Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (4 of 9) Example of Type I exotoxin – Superantigens ▪ Pyrogens ▪ Overstimulate the immune system to cause massive inflammation that harms the host Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (5 of 9) Type II exotoxins – Membrane-damaging toxins – Disrupt the host cell plasma membrane – Forms pores or removes phosphate head groups from phospholipids – Destabilizes the membrane – Cause cell lysis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (6 of 9) Type III exotoxins – Intracellular toxins – Bind to a receptor and enter the cell – Most exotoxins in this group are AB toxins ▪ B (binding) region ▪ A (active) portion exerts effects inside Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (7 of 9) Bacterium Secreted exotoxin Host cell Type I Type II Type III Toxin Plasma Pore membraneSignal propagated formation 3. inside the cell 1. Lipid hydrolysis Receptor 2. Receptor Toxin binds at host plasma Toxins disrupt host cell membranes by Binding portion (B) of toxin binds 1. membrane to generate a forming pores or breaking down plasma membrane. 2. Toxin enters cell, membrane lipids. signal that generates effects; often by endocytosis. 3. Active portion toxin doesn’t enter cell. (A)enters the host cell and exerts an effect. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (8 of 9) Table 10.3 Exotoxin Examples Exotoxin Examples Family Type I: Type 1: Superantigens made by certain Streptococcus and Staphylococcus species Membrane- cause toxic shock syndrome (T SS). acting Staphylococcus aureus enterotoxins cause food poisoning. extracellular toxins Certain E. coli strains make heat-stable enterotoxins that cause diarrhea. Erythrogenic toxins made by Streptococcus pyogenes; damage skin capillaries to produce a red rash characteristic of scarlet fever. Type 2: Type II: Type II: Hemolysins: hemolytic toxins that lyse red and white blood cells to interfere with Membrane- host immune response. Streptolysins are hemolysins made by certain streptococcal damaging species. toxins Cytolysins interfere with host immune response by lysing white blood cells; they also may target general host cells to damage tissues; pneumolysins made by Streptococcus pneumonia (pneumonia, septicemia, meningitis) are an example. Phospholipases are made by many bacteria, including Clostridium perfringens (gas gangrene), Pseudomonas aeruginosa (wound infections and pneumonia), and Staphylococcus aureus (skin/wound infections; pneumonia; sepsis). Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exotoxins (9 of 9) Table 10.3 [Continued] Exotoxin Examples Family Type Type three:III: Diphtheria toxin; cytotoxin made by Corynebacterium diphtheria (diphtheria); Intracellular blocks protein synthesis. toxins Pertussis toxin: cytotoxin made by Bordetella pertussis, which causes whooping cough; suppresses host immune response. Cholera toxin: enterotoxin made by Vibrio cholerae; induces a watery diarrhea. Botulinum toxin: neurotoxin made by Clostridium botulinum; causes flaccid paralysis. Tetanospasmin: neurotoxin made by Clostridium tetani; causes contractile paralysis that gives tetanus its common name, “lock-jaw.” Copyright © 2023 Pearson Education, Inc. All Rights Reserved Five Steps to Infection (1 of 3) After reading this section, you should be able to: Identify the five tasks a pathogen must complete to successfully infect a host. Identify various portals of entry and exit. Name some adhesins and invasins and describe their roles in establishing infections. Discuss the most common tools that pathogens use to obtain nutrients. Describe the various mechanisms that pathogens may use to avoid immune detection and elimination. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Five Steps to Infection (2 of 3) After reading this section, you should be able to: Explain the relationship between symptoms and mode of transmission. Define the term reservoir and provide examples of environmental and organismal reservoirs. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Five Steps to Infection (3 of 3) To establish an infection, a successful pathogen must complete five general tasks: 1. Enter the host 2. Adhere to host tissues 3. Invade tissues and obtain nutrients 4. Replicate while warding off immune defenses 5. Transmit to a new host Copyright © 2023 Pearson Education, Inc. All Rights Reserved First, a Pathogen Must Enter a Host (1 of 2) Portal of entry: any site that a pathogen uses to enter the host – Mucous membranes are the most common portal of entry – Site where disease develops (but not necessarily the only or the main site affected) – Some pathogens have >1 portals of entry Copyright © 2023 Pearson Education, Inc. All Rights Reserved First, a Pathogen Must Enter a Host (2 of 2) Otic Ocular Outer ear infection Conjunctivitis (various by P. aeruginosa bacteria and viruses) (Swimmer’s ear) Skin Respiratory Mucosa S. aureus wound Pertussis infection Measles Influenza Parenteral GI Mucosa Hepatitis B and C Cholera Salmonella C. difficile Urogenital / Reproductive System Transplacental Genitalia: Urinary: HIV Gonorrhea Bladder, kidney Rubella Chlamydia and urethra Toxoplasmosis Certain infections papillomaviruses (E. coli) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Skin, Ocular, Otic, and Parenteral Entry (1 of 2) Integumentary system – Based on overall weight and surface area is the largest body system – Consists of skin, hair, nails, and associated glands – Blocks most microbes Pathogens have developed virulence factors that penetrate the integumentary system Copyright © 2023 Pearson Education, Inc. All Rights Reserved Skin, Ocular, Otic, and Parenteral Entry (2 of 2) Pathogens get in through…. – Otic entry – Abrasions – Physically boring through skin – Invade the conjunctiva – Bites – Cuts – Injections – Surgical incisions Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Entry Respiratory tract is the most common portal of entry – Coughing and sneezing suspends pathogens in the air as respiratory droplets – Infectious agents stirred up from dust or soil However, a pathogen that enters through the respiratory tract does not necessary establish an infection there Copyright © 2023 Pearson Education, Inc. All Rights Reserved Gastrointestinal (GI) Tract Entry Digestive system pathogens – Frequently have a fecal–oral transmission – Invade the mucosal surfaces of the GI tract – In contrast to respiratory tract entry, many pathogens that don’t enter via the GI tract eventually cause GI symptoms Copyright © 2023 Pearson Education, Inc. All Rights Reserved Urogenital Tract and Transplacental Entry Most sexually transmitted pathogens enter through the mucosal lining of the vagina or cervix in women or the urethra in men Certain sexually transmitted pathogens invade through the skin of the genitalia Pathogens that cause urinary tract infections invade the urethra in men and women Some pathogens exhibit vertical transmission by transplacental entry Copyright © 2023 Pearson Education, Inc. All Rights Reserved Second, a Pathogen Must Adhere to Host Tissues After entering a host, the pathogen must next adhere to host tissues Initial adhesion is often nonspecific, such as through hydrophobic interactions After nonspecific anchoring, the agent may target an exact surface molecule on the host cell Species and tissue tropism is due to specificity for a particular host cell surface marker Copyright © 2023 Pearson Education, Inc. All Rights Reserved Adhesion Factors (1 of 2) Adhesins are virulence factors used to stick to host cells in a specific or nonspecific manner Bacterial adhesins include cell wall components, capsules, fimbriae and pili, a variety of plasma membrane–associated molecules Copyright © 2023 Pearson Education, Inc. All Rights Reserved Adhesion Factors (2 of 2) Table 10.4 Some Examples of Pathogen Adhesins Adhesin Mechanism Examples Fimbriae or pili Extracellular hair-like E. coli GI and urinary system infections appendages that bind Pseudomonas aeruginosa respiratory and wound infections carbohydrates on host cells Neisseria gonorrhoeae (gonorrhea) Vibrio vulnificus deep wound infections like cellulitis and necrotizing fasciitis Sialic acid Surface molecules that Rotaviruses (G I infections) binding factors bind to sialic acid (diverse Influenza viruses acidic sugar molecules on Aspergillus fumigatus (fungal lung infection) host cells) Plasmodium falciparum (malarial parasite) Heparan and Factors that target host cell Borrelia burgdorferi (Lyme disease) heparin sulfate heparan and heparin Helicobacter pylori (gastric ulcers) binding factors sulfate (acidic sugary Human immunodeficiency virus (H IV/AIDS) molecules that are present Herpes simplex viruses in many cells and tissues) Fibronectin Assorted surface Streptococcus pyogenes (“strep” throat) binding factors molecules that bind to the Staphylococcus aureus (“staph” infections) protein fibronectin in host Mycobacterium tuberculosis (tuberculosis) epithelial tissues Clostridioides difficile (infectious diarrhea) Candida albicans (yeast infection) Leishmania species (protozoan infection leishmaniasis) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biofilms and Quorum Sensing (1 of 2) Bacteria form biofilms on almost any natural or manmade surface According to the NIH, 60–80% of human infections originate from biofilms Common places for healthcare-acquired biofilm formation include: – Implanted devices (e.g., catheters, implanted prosthetic joints) – Rocky deposits in the kidneys (kidney stones) or gallbladder (gallstones) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biofilms and Quorum Sensing (2 of 2) Subveno us Dental catheter plaque Kidney stones Artifical hip implant Biofilm on urinary catheter Copyright © 2023 Pearson Education, Inc. All Rights Reserved Third, a Pathogen Must Invade Tissues and Obtain Nutrients (1 of 2) Once a pathogen enters the host and adheres to tissues, it must obtain nutrients Following adhesion, the pathogen has several options: – Stay on the surface of the host cell – Pass through cells to invade deeper tissues – Enter cells to reside as an intracellular pathogen As pathogens invade, they tend to damage host tissues and generate cytopathic effects Copyright © 2023 Pearson Education, Inc. All Rights Reserved Third, a Pathogen Must Invade Tissues and Obtain Nutrients (2 of 2) Once adhered, Pathogens a pathogen may: Host cell Remain on the surface Reside in the cell Deeper in the tissue Invade deeper by passing through cells...... or passing between cells Copyright © 2023 Pearson Education, Inc. All Rights Reserved Invasins and Motility (1 of 2) Invasins – Allow pathogens to invade host tissues – Local-acting factors – Extracellular enzymes that pathogens secrete – Mechanism of action: ▪ Break down host tissues ▪ Form blood clots ▪ Induce the host to uptake the pathogen Motility – Important invasion strategy that helps a pathogen spread Copyright © 2023 Pearson Education, Inc. All Rights Reserved Invasins and Motility (2 of 2) Table 10.5 Invasin Examples Invasin Mechanism Examples Flagella Motility enhances spread; molecular E. coli (G I and urinary system infections) features of flagella may assist adhesion Vibrio vulnificus (deep wound infections like cellulitis and necrotizing fasciitis) Collagenases Enzymes that break down collagen, an Clostridium perfringens (gas gangrene) important structural protein in tissues, Vibrio vulnificus (deep wound infections like allowing for invasion of new host areas cellulitis and necrotizing fasciitis) Streptococcus mutans (dental caries; periodontal disease) Neuraminidases Enzymes that break down neuraminic acid, Vibrio cholerae (cholera) which has important roles in regulating host Influenza virus cell communications and membrane Hemophilus influenza transport. Damage disrupts normal and (pneumonia/epiglottitis/Hib disease meningitis) immune cell functions. Coagulases Enzyme that promotes blood clotting to form Staphylococcus aureus (skin/wound a protective layer around the pathogen infections; pneumonia; sepsis) Streptococcus faecalis (urinary tract infections; meningitis; endocarditis) Kinases Enzymes that break down blood clots to Streptococcus pyogenes (“strep” throat) allow pathogens to spread out of clots that Staphylococcus aureus (skin/wound may trap them infections; pneumonia; sepsis) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tools to Obtain Nutrients: Siderophores and Extracellular Enzymes (1 of 2) Most cellular pathogens require iron to survive In humans, very little iron freely circulates in tissues and blood – Transferrin binds to iron and shuttles it to tissues Many bacteria produce siderophores that snatch iron from transferrin Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tools to Obtain Nutrients: Siderophores and Extracellular Enzymes (2 of 2) Many bacteria and fungi also make extracellular enzymes – Break down nutrients in the local environment – Allows pathogens to scavenge nutrients as they damage host tissues – Examples: ▪ Lipases—break down lipids ▪ Proteases—break down proteins Copyright © 2023 Pearson Education, Inc. All Rights Reserved Cytopathic Effects in the Host (1 of 3) Pathogens can damage host cells and generate cytopathic effects – Cytocidal—kill the cell – Noncytocidal—damage the cell Copyright © 2023 Pearson Education, Inc. All Rights Reserved Cytopathic Effects in the Host (2 of 3) Bacteria induce cytopathic effects as they: – Invade host cells – Release toxins – Exploit host nutrients Viral pathogens generate cytopathic effects when they: – Disrupt normal host cell function – Release from the host cell – Transform normal cells into cancer cells Copyright © 2023 Pearson Education, Inc. All Rights Reserved Cytopathic Effects in the Host (3 of 3) The immune system also inflicts damage on the body as a by-product of fighting infections Examples: – Tissue damage that develops in tuberculosis is due to the immune system attacking cells infected with the bacteria – Most viral infections result in the immune system killing virus-infected cells Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fourth, a Pathogen Must Evade Host Immune Defenses So It Can Replicate A pathogen must evade the immune system so it can safely replicate Table 10.6 Key Mechanisms for Escaping Host Immune Defenses Approach Examples Hide Antigen masking, mimicry, and variation Latency Intracellular lifestyle Undermine Suppress immune function ▪ Break down antibodies ▪ Infect immune system cells ▪ Block immune system signals ▪ Inhibit production of immune system factors Avoid phagocytosis ▪ Make a capsule ▪ Block phagosome–lysosome fusion ▪ Neutralize hydrolytic enzymes in phagocytes ▪ Secrete toxin that damages phagocytic cells ▪ Evolve to thrive inside the phagolysosome Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hiding From Host Immune Defenses (1 of 5) Intracellular pathogens – Include all viruses, many protozoans, and some bacterial pathogens – Spend a majority of their time inside host cells – Examples of intracellular bacteria include: ▪ Listeria monocytogenes ▪ Mycobacterium tuberculosis ▪ Salmonella species Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hiding From Host Immune Defenses (2 of 5) Latency – Ability of a pathogen to quietly exist inside a host – Usually causes persistent or recurrent disease – Examples: ▪ Herpes viruses (intermittent flare-ups) ▪ HIV (genetic hitchhikers) – Latent state protects pathogen from immune system – Can confer protection from drug therapies Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hiding From Host Immune Defenses (3 of 5) Antigenic masking – Upon entering the host, the pathogen may conceal antigenic features – Coats itself with host molecules Antigenic mimicry – Emulating host molecules – Capsules can resemble host carbohydrates Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hiding From Host Immune Defenses (4 of 5) Antigenic variation – Periodically altering the surface molecules – Prevents a rapid immune response – Causes include: ▪ Mutations in the genome ▪ Change in protein expression Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hiding From Host Immune Defenses (5 of 5) Antigen masking Antigens Pathogen The pathogen covers itself in host antigens to avoid immune detection. Antigen mimicry The pathogen manufactures antigens that resemble host antigens, helping it evade immune detection. Antigen variation The pathogen switches its antigens, thwarting the mounting immune response. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Undermining the Host Immune Response (1 of 4) Even if a pathogen can’t avoid immune detection, it could limit the immune system’s actions by: – Interfering with phagocytosis – Suppressing the immune response Copyright © 2023 Pearson Education, Inc. All Rights Reserved Undermining the Host Immune Response (2 of 4) Interference of phagocytosis – Phagocytes engulf and then destroy pathogens with hydrolytic enzymes – Some pathogens avoid phagocytosis by: ▪ Making a capsule ▪ Bursting free of the phagosome ▪ Blocking fusion of the phagosome with the lysosome ▪ Neutralizing enzymes of the phagocytes ▪ Damaging phagocytic cells using toxins Copyright © 2023 Pearson Education, Inc. All Rights Reserved Undermining the Host Immune Response (3 of 4) Interference of phagocytosis – Pathogen may have evolved to thrive inside the harsh environment of the phagolysosome Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 10.9 Escaping Phagocytosis Hydrolytic Pathogen enzymes Phagocytosis Phagosome Lysosome Phagocyte Phagolysosome Pathogens escape phagocytosis by... Releasing toxins that Avoiding phagocytosis kill phagocytes with a capsule Toxins Capsule Blocking fusion of lysosomeEscaping phagosome and with phagosome living in phagocyctic cell Phagolysosome Adapting to harsh environment of phagolysosome or neutralizing hydrolytic enzymes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Undermining the Host Immune Response (4 of 4) Immune suppression – Pathogens suppress immune function by: ▪ Directly targeting immune system cells ▪ Making proteases that break down host antibodies ▪ Interfering with transcription of interleukins ▪ Interfering with the molecular signaling that activates parts of the immune response Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fifth, a Pathogen Must Be Transmitted to a New Host to Repeat the Cycle The last crucial step in a pathogen’s success is transmission to a new host Sometimes the symptoms a pathogen generates facilitate transmission to others – Itchiness – Sneezing – Coughing – Diarrhea Copyright © 2023 Pearson Education, Inc. All Rights Reserved Exiting the Host Any route a pathogen uses to exit its host is a portal of exit – Feces, urine, and bodily fluids such as blood or fluids drained from wounds, vomit, saliva, mucus, or semen The portal of entry used by a pathogen is often the same as the portal of exit Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 10.10 Portals of Exit Otic Ocular Pus or drainage Itchy eyes stimulate may contain rubbing which transfers infectious agent pathogen to the hands Skin Respiratory Mucosa Pus or wound drainage Sneezes and coughs; may be rich in pathogens mucus discharge from nose or mouth Parenteral GI Mucosa Blood-borne pathogens Infectious agents in excrement, saliva, and mucosal secretions Urogenital Urine, semen, vaginal secretions Copyright © 2023 Pearson Education, Inc. All Rights Reserved Maintaining a Reservoir The pathogen’s reservoir could be: – Environmental niche (e.g., soil or water) – An organism (e.g., humans or animals) – Fomites Copyright © 2023 Pearson Education, Inc. All Rights Reserved Safety and Health Care After reading this section, you should be able to: Identify the basic criteria for assigning pathogens to a biosafety level. Describe features of each biosafety level (B SL) and give examples of pathogens for each B SL. Discuss what standard precautions entail. Name the three main categories of contact precautions and explain what each entails. Explain what healthcare workers can do to manage outbreaks. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Levels Dictate Appropriate on-the- Job Behaviors in Healthcare (1 of 2) Healthcare and laboratory personnel regularly come in close proximity with biological hazards Not all agents present the same level of danger Biosafety level (BSL) is based on numerous criteria, with the following key considerations: – Level of infectivity – Extent of disease caused and mortality rates – Mode of transmission – Availability of preventions and treatments Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Levels Dictate Appropriate on-the- Job Behaviors in Healthcare (2 of 2) There are four biosafety levels: – BSL-1 – BSL-2 – BSL-3 – BSL-4 Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 1 BSL-1 agents – Well characterized – Rarely cause disease in healthy people – Pose limited risk – Examples: ▪ Bacillus subtilis ▪ E. coli K-12 strains ▪ Staphylococcus epidermidis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 2 (1 of 2) BSL-2 agents – Infectious agents; not airborne – Human bodily fluids are treated as BSL-2 – Examples: ▪ Staphylococcus aureus ▪ Herpes simplex viruses ▪ Most influenza strains ▪ Clostridium tetani ▪ Salmonella species Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 2 (2 of 2) BSL-2+ agents – Dangerous and incurable – Not vaccine preventable – Examples: ▪ HI V – Note: ▪ These pathogens are managed in BSL-2 facilities since they are not airborne ▪ Require additional safety practices Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 3 (1 of 2) BSL-3 agents – Serious or lethal human diseases – Many have airborne transmission – Some are treatable, but high severity – 2,000 BSL-3 facilities across the United States – Entry to a BSL-3 area is restricted Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 3 (2 of 2) Face shield BSL-3 agents or goggles Isolation gown – Requires specialized personal protective equipment (PPE) – Examples: ▪ Coxiella burnetii ▪ Mycobacterium One pair of clean, N95 or higher respirator When respirators are not tuberculosis non-sterile gloves available, use the best available alternative, like a facemask. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Biosafety Level 4 BSL-4 agents – Dangerous and “exotic” pathogens – Tend to be lethal in humans – No cures or treatments – 15 BSL - 4 facilities in the United States – Examples: ▪ Ebola ▪ Marburg Copyright © 2023 Pearson Education, Inc. All Rights Reserved Table 10.7 U.S. General Biosafety Level Precautions (1 of 2) Level Minimum Personal Protection Examples of Lab Facility Considerations Equipment (P PE) Required (not comprehensive) BSL-1 None Hand-washing sinks must be available Work may be done on open lab bench No food, beverages, or chewing gum in the lab WPUNJ qualifies BSL- 2 Lab coats and gloves (safety All BSL-1 measures, plus: glasses/face shield if splash risk) Most agents worked on at open lab bench spaces BSL-2+ agents like dengue virus, Biological safety cabinet needed when working with certain hepatitis C virus, Salmonella BSL-2 agents or samples, like tissues or bodily fluids, that enterica serotype Typhi, rabies may contain such agents virus, Zika virus, and H IV require additional precautions. Limit lab access Biohazard signage (signs indicating biosafety level, agents used, emergency contact personnel, etc.) Eye-wash stations must be present Lab design should allow easy cleaning and decontamination (no carpets, upholstery, etc.) Autoclave (a specialized machine for sterilizing) WPUNJ qualifies Copyright © 2023 Pearson Education, Inc. All Rights Reserved Table 10.7 U.S. General Biosafety Level Precautions (2 of 2) Table 10.7 [continued] Level Minimum Personal Protection Examples of Lab Facility Considerations (not Equipment (PPE) Required comprehensive) BSL-3 Protective lab covering All BSL-1 and -2 measures, plus: Gloves Agents manipulated in biological safety cabinet Respirators if indicated Controlled access/authorized personnel Must wear P PE at all times People entering area warned of risks, vaccinated (if PPE worn for B SL-3 work should not be possible), and monitored for infection worn in other areas Decontaminate all waste Monitoring to ensure the worker has not Decontaminate lab wear before laundering been infected Special airflow management Self closing, double door access Not at WPUNJ BSL-4 Airtight, pressurized, full-body hazardous All BSL-1, -2, and -3 measures, plus: material suits; air is piped into the suit Specialized facility design and engineering through a specialized air delivery system Highly restricted/lockdown access Clothing changes and showers before entering and leaving facility Not at WPUNJ Copyright © 2023 Pearson Education, Inc. All Rights Reserved Infection Control Practices Protect Both Workers and Patients in Healthcare Facilities Most healthcare facilities have an infection control team that strives to limit infection risks for healthcare workers and patients – Standard precautions – Transmission precautions Copyright © 2023 Pearson Education, Inc. All Rights Reserved Standard Precautions (1 of 2) 1980s, healthcare facilities adopted universal precautions CDC later expanded the universal precautions and called them standard precautions – Limit transmission of bloodborne pathogens – All patients are treated as potential sources of bloodborne or other infectious agents – Handling precautions exist for all bodily fluids (e.g., blood, feces, nonintact skin, excretions, secretions except sweat) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Standard Precautions (2 of 2) Universal and standard precautions include: – Hand washing before and after each patient contact – Change gloves between tasks or procedures – Barrier clothing and face shields or masks – Proper management of biosharps waste – Disinfection of surfaces, laundry, and garments Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission Precautions (1 of 5) Transmission precautions – Prevent direct contact, droplet, and airborne disease transmission – Apply when a specific infectious agent is suspected or known to be present – Signage is posted to inform healthcare providers and visitors of necessary precautions Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission Precautions (2 of 5) Contact precautions – Minimize transmission of infectious agents spread by fomites and healthcare workers – Barrier gowns and gloves worn – Disinfection practices increase – Patient transport is limited – Noncritical equipment dedicated for single-patient use – Examples: MRSA and C. difficile Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission Precautions (3 of 5) Droplet precautions – Procedural mask when in the patient’s room – Limit patient transport – During transport the patient wears a mask – Example: ▪ Rubella ▪ Influenza ▪ Pertussis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission Precautions (4 of 5) Airborne precautions – Airborne infection isolation room (AIIR) – Specialized pressure systems – Examples: ▪ Tuberculosis ▪ Chickenpox ▪ Measles Copyright © 2023 Pearson Education, Inc. All Rights Reserved Transmission Precautions (5 of 5) Airborne Model number Flexible metal nose piece precautions For a snug fit across the full Manufacturer bridge and sides of the nose – People name entering AII Lot number Rs must NIOSH name wear air- Always block letters Headband or NIOSH logo NIOSH approved purifying respirators do not have ear loops, instead a headband respirators holds the respirator snugly against the face Filter Designation TC-Approval number Let er t code: Required on all prodcuts made N = Not oil resistant after September 2008 R = Oil resistant P = Oil proof Numerical code: 95 = blocks at least 95% of airborne particles 99 = blocks at least 99% of airborne particles 100 = blocks at least 99.7% of airborne particles Copyright © 2023 Pearson Education, Inc. All Rights Reserved Figure 10.13 Standard Precautions and Transmission Precautions Standard precautions (used with all patients) Hand hygiene Gloves if risk of exposure to wounds, bodily fluids, or mucous membranes Barrier gowns and face shields when splash risk Disinfection Transmission precautions Contact Precautions Droplet Precautions Airborne Precautions Wound/skin infectionMost respiratory infectionsTuberculosis Resistant infection Influenza Rubeola (measles) Infectious diarrhea Pertussis Varicella (chickenpox) Limit patient Limit patient Limit patient transport transport transport Special attention to N95 or Procedural hand washing mask at all times comparable respirator Gloves at all times Place patient in AIIR facility Gown at all times Single patient use equipment Copyright © 2023 Pearson Education, Inc. All Rights Reserved Visual Summary: Host–Microbe Interactions and Pathogenesis 1 Entry Virulence Factors Virulence factors help a pathogen accomplish the five steps at left. Otic Ocular NUTRIENT ADHESION ACQUISITION INVASION Respiratory Mucosa Skin TOXINS IMMUNE SYSTEM EVASION Parenteral ethal L dose-50 Infectious dose-50 GI Mucosa The lethal dose-50 is the The infectious dose-50 amount of toxin neededdescribes to how many cells or kill 50% of affected hosts virions are needed to establish that are not treated. an infection in 50% of exposed susceptible hosts. Urogenital / Transplacental Reproductive System Exotoxins Bacterium Secreted exotoxin 2 Adhesion Pathogens Host cell Host cell 3 Invasion Invasins help the pathogen spread deeper into Type I: Toxin binds at host plasma membrane. Type II: Toxin disrupts host cell membranes. host tissues. Siderophores and extracellular Type III: Toxin enters cell, often by endocytosis. enzymes help cellular pathogens obtain Deeper in nutrients so they can propagate. the tissue Safety Limit infection! Always follow standard 4 Evasion precautions and transmission precautions. Hide from immune defenses Undermine immune defenses Intracellular lifestyle Suppress immune function Gloves if risk of Latency Avoid phagocytosis Hand hygiene exposure to wounds, Antigen masking, mimicry, and variation bodily fluids, or mucous membranes Barrier gowns and face shields Disinfection Antigen masking Phagocyte when splash risk Host Cell Antigen variation Biosafety levels are assigned based on pathogenic features of the agent in question. Antigen mimicry 5 Exit and Transmission Portals of exit are determined by transmission mode and are Biosafety levels often (though not always) the same as the portal of entry. BSL-1 Minimal risk BSL-2 BSL-3 BSL-4 Highest risk Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (1 of 6) Summary of the case: – Max went surfing during summer in Fort Meyers, Florida – A week prior, Max cut his hand cooking dinner – The wound was not deep, healing, scabbed over, itchy, but painless – After surfing, Max noticed the scab had softened and looked much better than it had in days – By 5:00 p.m. that evening, Max felt achy and his upper arm and hand were sore – The scab area had reddened and become tender, swollen, and warm to the touch – He also felt a bit nauseous Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (2 of 6) Summary of the case: – Exhausted, feverish, and nauseous, Max skipped dinner and went to bed early – At 8:30 p.m. his mom told him to go to the emergency room right away – Max was 33 and in perfect health aside from the infection – The ER doctor was concerned about his condition – Max was admitted to the hospital – Max underwent wound management, intravenous antibiotic therapy, and monitoring Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (3 of 6) Summary of the case: – By the morning, Max had a heartbeat of 105 beats per minute (tachycardia), a temperature 101.4 F, and remained nauseous of – Despite ongoing intravenous volume resuscitation, Max was hypotensive, his arm was swollen and appeared eccyhmotic – Hemorrhagic bullae (large blood-filled blisters) were evident – Max was also in excruciating pain that morphine barely dulled – The attending physician suspected Max had necrotizing fasciitis ▪ Soft tissue infection usually caused by Gram-positive group A streptococci – Microbiology report confirmed Gram-negative bacterium called Vibrio vulnificus Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (4 of 6) Summary of the case: – Vibrio vulnificus has a number of virulence factors (capsule, collagenases, proteases, and lipases; motility; adhesins, invasins, toxins) – Max was taken into surgery for wound debridement – Following surgery Max was moved to the ICU – He endured several additional wound debridement procedures and a skin graft – Max was told that his age and general overall health would likely lead him to a full recovery – Max’s arm would required rehabilitation, but he eventually regained full use of the affected arm Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (5 of 6) 1. Based on the microbiology report and Max’s signs and symptoms, what toxin-based complication was Max’s healthcare team most likely concerned could develop? Explain your reasoning. 2. Explain how V. vulnificus’s virulence factors contributed to the pathology described in the case. 3. In Max’s illness, what was the likely reservoir and source of the pathogen V. vulnificus? 4. What portal of entry did V. vulnificus most likely use? Explain your reasoning. 5. What infection control precautions were most likely used when managing Max’s health in the ICU? Discuss how you came to your conclusions. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Think Clinically: Be S.M.A.R.T. About Cases (6 of 6) 6. To which biosafety level is V. vulnificus most appropriately assigned? Explain your reasoning. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Copyright This work is protected by United States copyright laws and is provided solely for the use of instructors in teaching their courses and assessing student learning. Dissemination or sale of any part of this work (including on the World Wide Web) will destroy the integrity of the work and is not permitted. The work and materials from it should never be made available to students except by instructors using the accompanying text in their classes. All recipients of this work are expected to abide by these restrictions and to honor the intended pedagogical purposes and the needs of other instructors who rely on these materials. Copyright © 2023 Pearson Education, Inc. All Rights Reserved