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Overview of Human-Microbial Interactions
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Most microorganisms are benign
Humans colonized by microorganisms at birth
Animals provide favorable environment for growth of many microorganisms
Infections frequently begin at sites of animal's mucous membranes
Humans colonized by microorganisms at birth
Animals provide favorable environment for growth of many microorganisms
Infections frequently begin at sites of animal's mucous membranes
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Normal Microbial Flora
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Microorganisms usually found associated with human body tissue
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Pathogens
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Microbial parasites
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Pathogenicity
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The ability of a parasite to inflict damage on the host
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Virulence
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Measure of pathogenicity
Relative ability of a pathogen to cause disease
Relative ability of a pathogen to cause disease
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Opportunistic Pathogen
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Causes disease only in the absence of normal host resistance
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Infection
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Situation in which a microorganism is established and growing in a host, whether or not the host is harmed
Availability of nutrients MOST IMPORTANT in affecting pathogen growth
Availability of nutrients MOST IMPORTANT in affecting pathogen growth
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Disease
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Damage or injury to the host that impairs host function
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Normal Microflora of the Skin
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Skin is a dry, acid environment that does not support growth of most microorganisms
-compared to sweat glands that readily colonize gram-positive bacteria
Skin microflora composition is influenced by environmental factors and host factors
-compared to sweat glands that readily colonize gram-positive bacteria
Skin microflora composition is influenced by environmental factors and host factors
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Normal Microflora of the Oral Cavity
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Oral cavity is a complex, heterogeneous microbial habitat
Saliva contains antimicrobial enzymes
-But high concentrations of nutrients near surfaces in the mouth promote localized microbial growth
-includes lysozymes (enzyme that cleaves glycosidic linkages in peptidoglycan of bacterial cell walls)
Saliva contains antimicrobial enzymes
-But high concentrations of nutrients near surfaces in the mouth promote localized microbial growth
-includes lysozymes (enzyme that cleaves glycosidic linkages in peptidoglycan of bacterial cell walls)
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Normal Microflora of the Oral Cavity (Teeth)
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The tooth consists of a mineral matrix (enamel) and surrounding living tissue (dentin and pulp)
-bacteria colonize teeth by attaching to acidic glycoproteins deposited on it by saliva
Extensive growth of oral microorganisms (especially streptococci) results in thick bacterial layer (dental plaque)
-as plaque develops, anaerobic bacterial species grow & produce high concentrations of acid = decalcification of the tooth enamel (dental caries)
Lactic acid bacteria Streptococcus sobrinus and Streptococcus mutans are common agents of dental caries
-bacteria colonize teeth by attaching to acidic glycoproteins deposited on it by saliva
Extensive growth of oral microorganisms (especially streptococci) results in thick bacterial layer (dental plaque)
-as plaque develops, anaerobic bacterial species grow & produce high concentrations of acid = decalcification of the tooth enamel (dental caries)
Lactic acid bacteria Streptococcus sobrinus and Streptococcus mutans are common agents of dental caries
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Normal Microflora of the Gastrointestinal Tract
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Human Gastrointestinal (GI) Tract
-consists of stomach, small intestines, large intestines
-responsible for digestion of food, absorption of nutrients, and production of nutrients by indigenous microbial flora
-contains 10^13 - 10^14 microbial cells
Acidity of the stomach and the duodenum of the small intestine (pH 2) prevent many organisms from colonizing the GI tract
-consists of stomach, small intestines, large intestines
-responsible for digestion of food, absorption of nutrients, and production of nutrients by indigenous microbial flora
-contains 10^13 - 10^14 microbial cells
Acidity of the stomach and the duodenum of the small intestine (pH 2) prevent many organisms from colonizing the GI tract
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Functions of the Intestinal Flora
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Carry out a variety of metabolic reactions that produce various compounds
The type and amount produced is influenced by the composition of the intestinal flora and diet
Compounds produced by intestinal flora include:
-vitamins
-gas, organic acids, odor
-enzymes
The type and amount produced is influenced by the composition of the intestinal flora and diet
Compounds produced by intestinal flora include:
-vitamins
-gas, organic acids, odor
-enzymes
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Normal Microflora of the Respiratory Tract
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Restricted group of organisms colonizes the upper respiratory tract
-include staphylococci, streptococci, diphtheroid bacilli, gram-negative cocci
Lower respiratory tract lacks microflora in healthy individuals
-as air passes into the lower respiratory tract, flow rate decreases and organisms settle onto walls of respiratory passages
-include staphylococci, streptococci, diphtheroid bacilli, gram-negative cocci
Lower respiratory tract lacks microflora in healthy individuals
-as air passes into the lower respiratory tract, flow rate decreases and organisms settle onto walls of respiratory passages
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Normal Microflora of Urogenital Tract
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Bladder is sterile in males and females
Altered conditions (change in pH) can cause potential pathogens in the urethra (E.coli and P.mirabilis) to multiply and become pathogenic
--usually cause UTIs in women
Vagina is weakly acidic and contains glycogen
-Lactobacillus acidophilus, organism in the vagina, ferments glycogen and produces lactic acid
-Lactic acid maintains a local acidic environment
Altered conditions (change in pH) can cause potential pathogens in the urethra (E.coli and P.mirabilis) to multiply and become pathogenic
--usually cause UTIs in women
Vagina is weakly acidic and contains glycogen
-Lactobacillus acidophilus, organism in the vagina, ferments glycogen and produces lactic acid
-Lactic acid maintains a local acidic environment
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Mechanisms of Pathogenesis
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Exposure -> adherence -> invasion -> colonization & growth -> toxicity/invasiveness -> tissue damage/disease
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Measuring Virulence
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Virulence estimated by LD50 (lethal dose 50)
-amount of an agent that kills 50% of animals in a test group
Highly virulent pathogens show little difference in the number of cells required to kill 100% or 50%
-amount of an agent that kills 50% of animals in a test group
Highly virulent pathogens show little difference in the number of cells required to kill 100% or 50%
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Attenuation
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Decrease or loss of virulence
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Toxicity
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Organism causes disease by means of toxin that inhibits host cell function or kills host cells
Toxins can travel to sites within host not inhabited by pathogen
Toxins can travel to sites within host not inhabited by pathogen
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Invasiveness
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Ability of a pathogen to grow in host tissue at densities that inhibit host function
-can cause damage without producing a toxin
-can cause damage without producing a toxin
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Pathogen Invasion
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Starts at the site of adherence
May spread throughout the host via the circulatory or lymphatic systems
May spread throughout the host via the circulatory or lymphatic systems
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Specific Adherence
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Pathogen must gain access to host tissues and multiply before damage can be done
Bacteria and viruses that initiate infection often adhere to epithelial cells through macromolecular interactions on the surfaces of the pathogen and the host cell
Bacteria and viruses that initiate infection often adhere to epithelial cells through macromolecular interactions on the surfaces of the pathogen and the host cell
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Bacterial Adherence
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Facilitated by:
-Extracellular macromolecules that are not covalently attached to the bacterial cell surface
---ex. slime layers and capsules
-fimbriae and pili
-Extracellular macromolecules that are not covalently attached to the bacterial cell surface
---ex. slime layers and capsules
-fimbriae and pili
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Pathogenic Invasion
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Pathogens produce enzymes that:
-enhance virulence by breaking down or altering host tissue to provide access to nutrients
---ex. hyaluronidase (enzyme that promotes spreading of organisms in tissue by breaking down polysaccharide hyaluronic acid-intercellular cement in animals)
-protect the pathogen by interfering with normal host defense mechanisms
---ex. coagulase (breaks down tissue supporting collagen network, spreading organism)
-enhance virulence by breaking down or altering host tissue to provide access to nutrients
---ex. hyaluronidase (enzyme that promotes spreading of organisms in tissue by breaking down polysaccharide hyaluronic acid-intercellular cement in animals)
-protect the pathogen by interfering with normal host defense mechanisms
---ex. coagulase (breaks down tissue supporting collagen network, spreading organism)
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Exotoxins
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Proteins released from the pathogen cell as it grows
Three categories:
-cytolytic toxins
-AB toxins
-superantigen toxins
Three categories:
-cytolytic toxins
-AB toxins
-superantigen toxins
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Cytolytic Toxins
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Work by degrading cytoplasmic membrane integrity, causing cell lysis and death
Toxins that lyse red blood cells are called hemolysins
Staphylococcal alpha-toxin kills nucleated cells and lyses erythrocytes (releases cytoplasmic components out of cell)
Toxins that lyse red blood cells are called hemolysins
Staphylococcal alpha-toxin kills nucleated cells and lyses erythrocytes (releases cytoplasmic components out of cell)
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AB Toxins
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Consist of two subunits, A and B
Inhibits protein synthesis
Works by binding to host cell receptor (B subunit) and transferring damaging agent (A subunit) across the cell membrane
Examples: diphtheria toxin, tetanus toxin, botulinum toxin
Inhibits protein synthesis
Works by binding to host cell receptor (B subunit) and transferring damaging agent (A subunit) across the cell membrane
Examples: diphtheria toxin, tetanus toxin, botulinum toxin
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Clostridium tetani & Clostridium botulinum
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Produce potent AB exotoxins that affect nervous system
C.tetani grows in the body in deep wounds that become anoxic
C.botulinum grows directly in the body, causing infant wound or botulism and grows and produces toxins in preserved foods
Botulinum toxin consists of related AB toxins that are potent biological toxins
Tetanus toxins are AB protein neurotoxins
C.tetani grows in the body in deep wounds that become anoxic
C.botulinum grows directly in the body, causing infant wound or botulism and grows and produces toxins in preserved foods
Botulinum toxin consists of related AB toxins that are potent biological toxins
Tetanus toxins are AB protein neurotoxins
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Enterotoxins
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Exotoxins whose activity affects the small intestines
Generally cause massive secretion of fluid into the intestinal lumen, resulting in vomiting and diarrhea
-ex. chloera toxin
Generally cause massive secretion of fluid into the intestinal lumen, resulting in vomiting and diarrhea
-ex. chloera toxin
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Endotoxins
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Lipopolysaccharide portion of the cell envelope of certain gram-negative Bacteria, which is a toxin when solubilized
Cell bound and released in large amounts only when the cells lyse
Generally less toxic than exotoxins
Presence of endotoxin can be detected by the Limulus amoebocyte lysate (LAL) assay
Cell bound and released in large amounts only when the cells lyse
Generally less toxic than exotoxins
Presence of endotoxin can be detected by the Limulus amoebocyte lysate (LAL) assay
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Compromised Host
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One or more resistance mechanisms inactive
Probability of infection increases
Age is important factor (old more susceptible)
Stress, diet, genetic conditions can also compromise a host
Probability of infection increases
Age is important factor (old more susceptible)
Stress, diet, genetic conditions can also compromise a host
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Innate Resistance
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Hosts have innate resistance to most pathogens
-natural host resistance, tissue specificity, physical/chemical barriers
-natural host resistance, tissue specificity, physical/chemical barriers
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Nasopharynx
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Removal of particles including microorganisms by rapid passage of air over cilia in nasopharynx
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Skin
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Physical barrier
Produces antimicrobial fatty acids and its normal flora inhibits pathogen colonization
Produces antimicrobial fatty acids and its normal flora inhibits pathogen colonization
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Stomach
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Stomach acidity (pH 2) inhibits microbial growth
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Urinary Tract
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Flushing of urinary tract prevents colonization
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Lysozyme
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In tears and other secretions dissolves cell walls
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Trachea
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Mucus and cilia lining in trachea suspend and move microorganisms out of the body
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Lungs
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Mucus and phagocytes in lungs prevent colonization
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Blood
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Blood and lymph proteins inhibit microbial growth