PATHOGENIC MICROBIOLOGY

Summary of Host-Parasite Interactions

 
I. NATURAL HABITATS FOR MICROBES

• Soil; Water; Air

• Animals and Animal Products

II. MICROBIAL FLORA OF HUMAN BODY

• Skin: Gram-positive bacteria are most common

• Respiratory Tract (actually external to body)

• Mouth and oropharynx

• Saliva

• Teeth and gums (gingiva)

• Nose and nasopharynx
• Microorganisms can be aspirated into the lower respiratory tract

• Larynx, trachea and bronchial tubes (bronchi)

• Lungs: Superior and inferior lobes (also middle lobe in right lung); Alveoli

• Eye (Conjunctivae)
• Ear: Inner, middle and exterior; Exterior commonly colonized

• Gastrointestinal Tract (actually external to body): Intestinal flora play a significant role in: Digestion; Vitamin production (e.g., vitamin K); Ecological competition (see below) with potentially pathogenic microorganisms

• Esophagus: Not typically colonized
• Gastric mucosa of stomach: Acid tolerant organisms
• Small intestine: Extends from pylorus to ileo-cecal junction (about 20 feet in length); Colonized by mostly anaerobes

• Villi (plural of villus) and microvilli are finger-like projections that protrude through the mucous membrane throughout the length of the small intestine and are responsible for absorption

• Peyer’s patch: Aggregations of lymphoid tissue concentrated in the ileum

• M (microfold) cells: specialized cells in the Peyer’s patches that sample the microenvironment and uptake foreign antigens for processing by underlying macrophages

• Duodenum: Upper portion of small intestine (about 10 inches in length) encompassing the superior, descending, transverse and ascending portions, in that order; Hepatic ducts (from liver), pancreatic duct, and cystic duct (from gallbladder) join and enter into the intestine at the descending duodenum

• Jejunum (middle portion): Upper two-fifths of remaining length of small intestine

• Ileum (lower portion): Remaining three-fifths of length of small intestine

• Large intestine: Extends from ileo-cecal valve to anus (about 5 feet in length); >10¹¹ bacteria per gram of feces with anaerobes 1000-fold more common than other microbes

• Cecum (a.k.a., Caecum): Large, blind pouch just posterior to the ileo-cecal junction

• Colon: Ascending, transverse, descending, and sigmoid portions

• Rectum

• Anus

• Special conditions of intestinal tract

• Intestinal tract of newborn

• Antibiotic alteration of flora

• Genitourinary Tract

• External genitalia
• Anterior urethra: Normally colonized by avirulent organisms; May be transiently colonized by fecal organisms that can cause disease; Neisseria gonorrhoeae and Chlamydia trachomatis may cause disease or asymptomatically colonize
• Urinary bladder: Not normally colonized; May be transiently colonized with urethral organisms
• Vagina: Microbial population influenced by hormones
• Cervix: Not normally colonized; Neisseria gonorrhoeae and Chlamydia trachomatis are important pathogens

III. NORMALLY STERILE SITES IN THE HUMAN BODY: Colonization of one of these sites generally involves a defect or breach in the natural defenses that creates a portal of entry

• Brain; Central nervous system

• Blood; Tissues; Organ systems

• Sinuses; Inner and Middle Ear

• Lower Respiratory Tract: Larynx; Trachea; Bronchioles (bronchi); Lungs; Alveoli

• Kidneys; Ureters; Urinary Bladder; Posterior Urethra

• Uterus; Endometrium (Inner mucous membrane of uterus ); Fallopian Tubes; Cervix and Endocervix

IV. ECOLOGY DEFINITIONS

• Ecological Niche: Unique environmental position occupied by a particular species, perceived in terms of actual physical space occupied and function performed within the community or ecosystem

• Flora (Microbiology Definition) = Microbiota: Microorganisms present in or characteristic of a special location (Flora more generically refers to plants; Fauna generically refers to animals)

• Normal flora = Indigenous or resident microbiota: Microbial flora typically occupying a particular niche; Organisms tend to segregate given diversity of environmental conditions; Many normal flora perform important functions for the host, including: digestive and nutritional functions and competition with pathogenic microorganisms
• Transient flora: Microbial flora only temporarily associated with a particular niche
• Endogenous flora: Microbial flora occupying niches that are in or on the body of the host
• Exogenous flora: Microbial flora normally existing externally to the body of the host

V. ECOLOGICAL RELATIONSHIPS

• Independence: Living free from the influence, guidance, or control by another organism

• Benign Relationship (Commensalism): Carrier

• Malignant Relationship (Parasitism): Disease

• Benign: Referring to a non-life or non-health threating condition; commensalism between host and parasite
• Carrier: Symptomless individual who is host to a pathogenic microorganim and has the potential to pass the pathogen to others
• Malignant: Disease tending to become progressively worse (Morbidity = illness) and potentially result in death (Mortality = death)

• Microbial Interactions: Complex relationships among species; Neutral, Antagonistic, or Synergistic

• Host-Parasite Interactions: Commensalism (+/0); Mutualism (+/+); Parasitism (+/-)

• Symbiosis: A relationship in which two dissimilar organisms (Symbiotes, Symbionts) live in close association with one another
• Commensalism: A relationship between two species in which one is benefited and the other is not affected, neither negatively nor positively
• Mutualism: Mutually beneficial relationship between two species
• Parasitism: A relationship between two species in which one benefits (Parasite) from the other (Host); Usually involves some detriment to the host

• True pathogen (a.k.a., Strict pathogen): Any microorganism capable of causing disease; An infecting agent

• Opportunistic pathogen: A usually harmless microorganism that becomes pathogenic under favorable conditions; Often a member of the normal microbial flora

VI. EPIDEMIOLOGY: Study of factors influencing occurrence, transmission, distribution, prevention and control of disease

• Epidemic: Occurring suddenly in numbers clearly in access of normal expectancy
• Endemic: Present or usually prevalent in a population or geographic area at all times
• Pandemic: Widespread epidemic distributed or occurring widely throughout a region, country, continent, or globally

• Acquiring Infectious Agents

• Portals (Routes) of entry: Ingestion, inhalation, direct penetration
• Carrier state: Symptomless individual (host) that is colonized by a pathogenic microorganism and who has the potential to pass the pathogen to others; Carriage may be transient or (semi-) permanent
• Nosocomial infections: Infection acquired in a hospital setting that was not present in the host prior to admission, generally occurring within 72 hours of admission
• Opportunistic infections: Infection caused by a normally harmless microorganism when certain predisposing conditions (disease or conditions that increase host susceptibility) exist

• Transmission of Disease

• Portals of entry/exit
• Vector: Living carrier, especially the animal that transfers an infectious agent from one host to another; Commonly an Arthropod
• Fomite: Inanimate object capable of transmitting microbes from one host to another, e.g., soiled bed linens, diapers, tissues and handkerchiefs, hospital respiratory equipment, etc.

VII. FACTORS CONTROLLING GROWTH OF ORGANISMS

• Nutrient Availabilty: The accessibility of a necessary resource, substance or compound providing nourishment to maintain life, i.e. capable of conversion to energy and structural building blocks

• Fastidious: an organism that has complex nutritional or cultural requirements, making isolation and culture more difficult

• Physico/Environmental Parameters

• Water activity/Osmotic pressure:

• Water activity (a_w): Represents the available water

• Osmotic pressure (p): Expressed in atmospheres; Reflects the concentration of solute in an aqueous solution

• Oxygen: Pathogenic microorganisms may have metabolic oxygen requirements that are Obligate or Facultative, Anaerobic or Aerobic, or somewhere in between, Microaerophilic
• pH: Power of hydrogen; Measurement of the amount of hydrogen ion in solution; Logarithm of the reciprocal of the hydrogen ion concentration in an aqueous solution used to express its acidity or alkalinity (0-14)
• Temperature:

• Psycrophile (psychrophilic): Liking cold temperatures; Optimal growth at 15o to 20oC

• Mesophile (mesophilic): Liking moderate temperatures; Optimal growth at 20o to 45oC

• Thermophile (thermophilic): Liking elevated temperatures; Optimal growth at 50o to 70oC

• Competition: Simultaneous demand by two or more organisms or species for a necessary, common resource or physical space (niche) that is in limited or potentially limited supply, resulting in a struggle for survival

• Host Immune System: The cells and tissues involved in recognizing and attacking foreign substances in the body

VIII. PATHOGENICITY vs. VIRULENCE

• Pathogenicity: Quality of producing or the ability to produce pathologic changes or disease

• Virulence: Measurement of the degree of disease producing ability of a microorganism as indicated by the severity of the disease produced; Measure of the dosage (inoculum size) required to caused a specific degree of pathogenicity; One general standard is the LD50

• Virulence factors: Microbial characteristics that enhance the ability to cause disease
• Dosage (Inoculum size): Number of pathogenic microorganisms entering the host
• LD50 = Lethal Dose 50: Number of microorganisms required to cause lethality in 50% of the test host

IX. INFECTION vs. DISEASE

• Infection: Colonization and/or invasion and multiplication of pathogenic microrganisms in the host with or without the manifestation of disease

• Colonization: Successful occupation of a new habitat by a species not normally found in this niche
• Multiplication: Ability of a microorganism to reproduce and increase in numbers during an infection

• Disease: Abnormal condition of body function(s) or structure that is considered to be harmful to the affected individual (host); Any deviation from or interruption of the normal structure or function of any part, organ, or system of the body; Dependent upon the dosage and virulence of the organism/agent and varies inversely with the resistance of the host

X. MICROBIAL PATHOGENICITY

• Factors that Influence the Degree of Pathogenicity and the Progression of Infection and Disease

• Host factors: Age, sex, ethnicity, nutrition (diet), hormonal status; personal hygiene and immune status; Underlying disease or medical condition; Antibiotic or drug usage; Presence of foreign object (e.g., splinter, catheter, sutures, etc.); Innate differences between hosts
• Microbial factors: Bacterial virulence factors; Inoculum size (dosage)
• External factors (e.g., crowding; seasonal variations; hygiene, sanitation and public health; food processing, storage and preparation; etc.)

• Progression of Infection and Disease

• Entrance (Portal of entry)
• Colonization (Adherence; Adhesion; Attachment)
• Multiplication with or without dissemination (spread)
• Penetration (Invasion) (Note: Not all pathogens are invasive)
• Signs and symptoms of disease (Morbidity; Mortality)
• Resolution or chronic state may be established
• Elimination and/or exit of pathogen (Carrier state may be established)

• Damage to Host

• Direct damage

• Tissue damage

• Cell components and metabolic by-products
• Toxins
• Enzymes

• Organ necrosis: Sum of morphological changes indicative of cell death and caused by the progressive degradative action of cellular components, metabolic by-products, enzymes and/or toxins

• Metabolic Effects: Pathogenic organisms can affect any of the body systems with disruptions in metabolic processes

• Indirect Damage: Damage to host from excessive or chronic immune response (immunopathogenesis)

XI. VIRULENCE FACTORS

• Colonization Factors

• Attachment/Adherence: Close association of bacterial cells and host cells generally characterized by receptors and target sites
• Surface Receptors/Target Sites: Receptor sites present on both host (Receptor) and bacterial surfaces (Adhesins)

• Adhesins: Bind Specific Host Receptors; Often involve fimbriae as structural cell component; Host cell receptors are often sugar moieties; Lectin: Adhesin specific for polysaccharide target receptor (sugar residues)

• Fimbriae (plural): Modern term for short, hair-like, protein (pilin) appendages extending outward from the surface of certain bacteria (formerly and a.k.a., pili)
• Pili (plural); Pilus (singular): Short, hair-like protein (pilin) appendages extending outward from the surface of certain bacteria; Term more properly applied to those organelles (F-pilus) responsible for bacterial conjugation (transfer of nucleic acids between closely related strains or species = "bacterial sex")

• Invasive Factors: Invasins enable a pathogenic microorganism to enter and spread throughout the cells and/or tissues of the host body; Specific recognition of receptor sites on target cells enhances pathogenic advantage

• Degradative Enzymes: Class of protein capable of catalytic reactions

• Bacterial growth requires food and energy: Growth is achieved by enzymatic catalysis of catabolic (breakdown) reactions of host tissues (resulting in tissue damage) linked to catalysis of anabolic (buildup) reactions in the bacterial cell

• Bacterial and host enzymes both play roles in the disease process

• Toxigenicity: the ability of a microorganism to cause disease as determined by the toxin it produces which partly determines its virulence

• Toxin-like pyrogenic (fever inducing) cell components (e.g., peptidoglycan and peptidoglycan fragments; Teichoic acid or lipoteichoic acid of Gram-positive cell wall)
• Endotoxin: Complex bacterial toxin; Lipid A portion of lipopolysaccharide from Gram-negative cell walls; LPS is composed of Lipid A + Core Polysaccharide + O Antigen (a.k.a., O polysaccharide side chain) and is released upon lysis of the cell during infection (FIGURE 3-11); Lipid A component is responsible for endotoxin activity effects on the host; O side chain is the antigenic portion of the LPS molecule

• Effects of endotoxin: Binds to specific receptors on macrophages, B lymphocytes (a.k.a., B cells) and other cells stimulating production and secretion of acute phase immunoreactants and lymphokines (e.g., IFN-gamma, IL-1, TNF-alpha, IL-6, histamine, prostaglandins); Stimulates growth of B cells (mitogenic)

• Lymphocyte: Agranular leukocyte that is concentrated in lymphoid tissue and is active in immunological responses in the body, including the production of lymphokines (cytokines) and antibodies

• Septic shock (sepsis): Endotoxemia; Endotoxin in the blood; Associated with overwhelming infection resulting in vascular system failure with sequestration of large volumes of blood in capillaries and veins; Activation of the complement and kinin systems and the release of histamines, prostaglandins, and other mediators may be involved
• Fever (Pyrogenicity): Any elevation of the body temperature above the normal; Functions to speed up immune reactions and to limit/slow bacterial growth and multiplication
• Leukopenia and then Leukocytosis: Abnormal reduction in the number (-penia) of leukocytes in the blood, (specifically a count of 5000 or less per cubic millimeter) / Abnormal increase in the number (-cytosis) of leukocytes in the blood, as during hemorrhage, infection, inflammation, or fever (specifically a count of 12,000 or more per cubic millimeter), respectively
• Activation of alternate complement pathway: C3a; C5a
• Increased vascular permeability (vasodilation); Decreased peripheral circulation; Decreased perfusion (blood flow) of blood to major organs

• Petechiae: Round, purple lesions caused by intradermal or submucosal microvascular hemorrhaging; capillary leakage; microhemorrhage
• Hypotension: Low blood pressure
• Shock

• Effects on metabolic and liver functions

• Decreased iron
• Hypoglycemia: Abnormally low glucose levels

• Activation of clotting pathway

• Thrombocytopenia: Abnormally low numbers of blood platelet
• Thrombosis: formation of blood clot (thrombus) in heart or blood vessel
• (DIC) Disseminated intravascular coagulation: Disorder characterized by a reduction in the elements involved in blood coagulation due to their utilization in widespread blood clotting within the vessels; Late stages marked by profuse hemorrhaging

• Shock: Characterized by failure of the circulatory system to maintain adequate blood flow to the vital organs; Symptoms include: Hypotension; Weak pulse; Rapid and shallow breathing; Low body temperature; CNS (central nervous system) effects (e.g., nausea)
• Death

• Exotoxins: Potent toxic substance formed and secreted extracellularly by species of certain bacteria; Genetic control can be encoded either chromosomally, on a plasmid, or by a lysogenic bacteriophage

• Toxoid: Toxin that can be altered with formaldehyde to lose physiological toxicity while retaining antigenicity; used as a vaccine

• Bacterial Cytolysins (a.k.a., Cytotoxins; Cytolytic toxins; Cytolytic enzymes): Responsible for hemolysis and tissue necrosis; May be lethal when administered intravenously

• Three major types based on mechanism of action:

• Hydrolyze membrane phospholipids (e.g., phospho-lipases of Clostridium, Staphylococcus)
• Thiol-activated cytolysins (oxygen-labile) alter membrane permeability by binding to cholesterol; e.g., Streptococcus, Clostridium
• Detergentlike activity on cell membranes; e.g. Staphylococcus, rapid rate of lysis

• Two-Component (Bipartite; Two domain) Toxins (A-B or A-5B): Usually one component is a receptor-binding domain (B) associated with absorption to target cell surface and transfer of active component across cell membrane; Second component is an enzymatic domain (A) (active component) that enzymatically disrupts cell function

• Conform to general structural model: Prototype is diphtheria toxin of Corynebacterium diphtheriae

• Bipartite structure (B, binding; A, active)
• Receptor-mediated endocytosis (host cell uptake and internalization of exotoxin
• ADP-ribosylation of intracellular target host molecule (e.g., host EF-2 (elongation factor-2) is ADP-ribosylated by C. diphtheriae exotoxin)

• Other types of exotoxins (e.g., PA, EF, LF protein toxins of Bacillus anthracis)

• Bacterial Defenses against Host Responses to Infection

• Encapsulation and antigenic mimicry, antigenic masking, and antigenic shift are important bacterial defense mechanisms
• Evasion or incapacitation of phagocytic and/or immune clearance

• Phagocytosis inhibitors: Mechanisms enabling an invading microorganism to resist being engulfed, ingested, and or lysed by phagocytes/ phagolysosomes; Patients with a defective/compromised monocyte-macrophage system (formerly, RES, reticuloendothelial system) are particularly susceptible to infection
• Capsule (Slime layer)

• Avoid recognition and killing

• Inhibit opsonization, chemotaxis, and/or phagocytosis
• Inhibit phagolysosomal fusion and/or resist lysosomal killing
• Block activation of phagocytes by interferon-gamma

• Destroy (lyse) phagocytic cell

• Inactivate/evade complement and antibody

• Evade alternate complement system
• Survive opsonization in presence of complement and PMNs and survive inside phagocytic cells
• Avoid antibody or proteolytically cleave immunoglobulins

• Avoid immune response by growing intracellularly

• Direct invasion of cells
• Resist lysosomal enzymes and antibacterial substances and multiply intracellularly
• Escape phagosome; Adapt to cytoplasmic growth

• Nonspecific T cell activation and/or mast cell stimulation: Bind TCR on T cell and MHCII on APC without presence of antigen; Life-threatening release of excess interleukins and mediators; Toxin-like, autoimmune-like responses or loss of immunoresponsiveness
• Induction of excess or chronic inflammation; Fibrosis (walling-off) of site of infection (e.g., granuloma formation seen in mycobacterial infections)
• Resistance to antibiotics: Intrinsic resistance; Plasmid-mediated; Chromosomally-mediated
   
  

BSCI 424 — Pathogenic Microbiology — BSCI 424 HomePage