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    Pharmaceutical Bacteriology

    J.E. Jose, RMT, MAEd, MSMTInstructor

    Department of Medical TechnologyFaculty of PharmacyUniversity of Santo Tomas

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    Just Checking Differentiate bacteria, viruses, fungi, protozoa, and

    parasites of medical importance based on fundamentalfeatures and characteristics. (CILO1)

    Compare the fundamental features of selected

    pharmaceutically important microorganisms. (CILO1) Determine the extent of occurrence of infectious diseasesand the severity of pathogenicity caused bymicroorganisms. (CILO3)

    Analyze the effect of microbial biofilms on the populations

    health. (CILO3) Recommend measures for the improvement of routine

    administration of vaccines as well as vaccines forindividuals in special risk categories. (CILO3)

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    BACTERIAL PATHOLOGY

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    What is the difference betweenpathogenicity and virulence?

    Pathogenicity is the potential to causedisease and is applied to groups orspecies of organismsVirulence is the degree of pathogenicitywithin a group or species and ismeasurable by the LD 50 .

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    LD50

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    Microbial Mechanisms of

    Pathogenicity

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    Pathogenicity - ability to cause diseaseVirulence - degree of pathogenicity

    Many properties that determine amicrobes pathogenicity or virulence areunclear or unknown

    But, when a microbe overpowers the hostsdefenses, disease results!

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    Portals of Entry

    1. Mucus Membranes

    2. Skin

    3. Parentarel

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    1. Mucus Membranes

    A. Respiratory Tract microbes inhaled into

    mouth or nose indroplets of moisture ordust particles

    Easiest and mostfrequently traveledportal of entry

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    Common Diseases contracted via

    the Respiratory Tract Common cold Flu Tuberculosis Whooping cough Pneumonia Measles Strep Throat Diphtheria

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    Mucus Membranes

    B. Gastrointestinal Tract microbes gain entrance thru

    contaminated food & wateror fingers & hands

    most microbes that enter

    the G.I. Tract are destroyedby HCL & enzymes ofstomach or bile & enzymesof small intestine

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    Common diseases contracted via theG.I. Tract

    Salmonellosis Salmonella sp.

    Shigellosis Shigella sp.

    Cholera Vibrio cholorea

    Ulcers

    Helicobacter pylori Botulism

    Clostridium botulinum

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    Fecal - Oral Diseases

    These pathogens enter the G.I. Tract at oneend and exit at the other end.

    Spread by contaminated hands & fingers orcontaminated food & water

    Poor personal hygiene.

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    Mucus Membranes of the Genitourinary System - STDs

    GonorrheaNeisseria gonorrhoeae

    Syphilis

    Treponema pallidum

    Chlamydia

    Chlamydia trachomatis

    HIV

    Herpes Simplex II

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    Mucus Membranes

    D. Conjunctiva mucus membranes that cover

    the eyeball and lines the eyelid

    Trachoma Chlamydia trachomatis

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    2nd Portal of Entry: Skin

    Skin - the largest organ of the body. Whenunbroken is an effective barrier for mostmicroorganisms.

    Some microbes can gain entrance thruopenings in the skin: hair follicles and sweatglands

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    3rd Portal of Entry: Parentarel

    Microorganisms are deposited into the tissuesbelow the skin or mucus membranes

    Punctures injections bites scratches surgery splitting of skin due to swelling or dryness

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    Preferred Portal of Entry

    Just because a pathogen enters your body itdoes not mean its going to cause disease.

    pathogens - preferred portal of entry

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    Preferred Portal of Entry

    Streptococcus pneumoniae if inhaled can cause pneumonia if enters the G.I. Tract, no disease

    Salmonella typhi if enters the G.I. Tract can cause Typhoid Fever if on skin, no disease

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    Number of Invading Microbes

    LD50 - Lethal Dose of a microbes toxin thatwill kill 50% of experimentally inoculated

    test animal ID50 - infectious dose required to cause

    disease in 50% of inoculated test animals Example: ID 50 for Vibrio cholerea 10 8 cells

    (100,000,000 cells) ID50 for Inhalation Anthrax - 5,000 to 10,000

    spores ????

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    How do Bacterial Pathogens

    penetrate Host Defenses?

    1. Adherence - almost all

    pathogens have a means toattach to host tissue

    Binding Sites

    adhesins

    ligands

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    Adhesins and ligands are usually on

    Fimbriae Neisseria gonorrhoeae ETEC (Entertoxigenic

    E. coli)

    Bordetello pertussis

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    2. Capsules

    Prevent phagocytosis attachment Streptococcus

    pneumoniae Klebsiella pneumoniae Haemophilus

    influenzae Bacillus anthracis Streptococcus mutans Yersinia pestisK. pneumoniae

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    3. Enzymes

    Many pathogens secrete enzymes thatcontribute to their pathogenicity

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    A. Leukocidins

    Attack certain types of WBCs

    1. Kills WBCs which prevents phagocytosis 2. Releases & ruptures lysosomes

    lysosomes - contain powerful hydrolyticenzymes which then cause more tissue damage

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    B. Hemolysins - cause the lysis of RBCs

    Streptococci

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    1. Alpha Hemolytic Streptococci

    - secrete hemolysins that cause theincomplete lysis or RBCs

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    3. Gamma Hemolytic Streptococci - donot secrete any hemolysins

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    C. Coagulase - cause blood to coagulate

    Blood clots protect bacteria from phagocytosisfrom WBCs and other host defenses

    Staphylococci - are often coagulase positive boils abscesses

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    D. Kinases - enzymes that dissolve blood clots

    1. Streptokinase - Streptococci 2. Staphylokinase - Staphylococci

    Helps to spread bacteria - Bacteremia

    Streptokinase - used to dissolve blood clots in the Heart(Heart Attacks due to obstructed coronary blood vessels)

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    E. Hyaluronidase

    Breaks down Hyaluronic acid (found in connectivetissues)

    Spreading Factor

    mixed with a drug to help spread the drugthru a body tissue

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    F. Collagenase

    Breaks down collagen (found in many connectivetissues)

    Clostridium perfringens - Gas Gangrene uses this to spread thru muscle tissue

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    G. Necrotizing Factor

    - causes death (necrosis) to tissue cells

    Flesh Eating Bacteria

    Necrotizing fasciitis

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    Summary of How BacterialPathogens Penetrate Host Defenses

    1. Adherence 2. Capsule 3. Enzymes

    A. leukocidins B. Hemolysins C. Coagulase D. Kinases E. Hyaluronidase F. Collagenase G. Necrotizing Factor

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    4. Toxins Poisonous substances produced by

    microorganisms toxins - primary factor - pathogenicity 220 known bacterial toxins

    40% cause disease by damaging the Eukaryoticcell membrane

    Toxemia Toxins in the bloodstream

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    2 Types of Toxins

    1. Exotoxins secreted outside the bacterial cell

    2. Endotoxins part of the outer cell wall of Gram (-) bacteria

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    Exotoxins

    Mostly seen in Gram (+) Bacteria

    Most gene that code for exotoxins are locatedon plasmids or phages

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    3 Types of Exotoxins

    1. Cytotoxins kill cells

    2. Neurotoxins interfere with normal nerve impulses

    3. Enterotoxins effect cells lining the G.I. Tract

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    Response to Toxins

    If exposed to exotoxins: antibodies against the toxin(antitoxins )

    Exotoxins inactivated ( heat, formalin or phenol) no

    longer cause disease, but stimulate the production ofantitoxin

    altered exotoxins - Toxoids Toxoids - injected to stimulate the production of

    antitoxins and provide immunity

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    Example: DPT Vaccine

    D - Diphtheria Corynebacterium diphtheriae

    P - Pertussis Bordetello pertussis

    T - Tetanus Clostridium tetani

    DPT - Diphtheria Toxoid

    Pertussis Antigen

    Tetanus Toxoid

    R i d I i i i Illi i

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    Required Immunizations in Illinois 1. Diphtheria

    2. Pertussis 3. Tetanus 4. Measles 5. Mumps 6. Rubella

    German Measles 7. Polio 8. Hib 9. Hepatitis B 10.Chicken Pox

    Corynebacterium diphtheriae Bordetello pertussis Clostridium tetani Measles virus Mumps virus Rubella virus

    Polio virus Haemophilus influenzae Hepatitis B Virus Varicella-zoster virus

    Type of Vaccines

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    Type of Vaccines D P

    T M M R Polio

    Salk Sabin

    Hib HBV

    Chicken Pox

    Toxoid Antigen Toxoid Attenuated Attenuated Attenuated IPV Inactivated Polio virus (Killed) 1953 OPV Oral Polio vaccine (attenuated) 1964 Conjugated vaccine Recombinant vaccine (antigen) yeast

    Capsid produced by geneticallyengineered yeast

    Attenuated

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    Most genes that code for exotoxins -plasmids or phages

    Lysogenic convergence Diphtheria Cytotoxin inhibits

    protein synthesis -resulting in cell death

    Pseudomembrane fibrin, dead tissue,

    bacterial cells

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    Lysogenic Convergence

    Scarlet Fever Streptococcus pyogenes

    lysogenic convergence prophage

    cytotoxin - damages blood capillaries and results in a skin rash Strep Thoat with a rash

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    Diseases caused by Neurotoxins

    Botulism Clostridium botulinum

    Gram (+), anaerobic, spore-forming rod, found in

    soil works at the neuromuscular junction prevents impulse from nerve cell to muscle cell

    results in muscle paralysisBotulus latin word for sausage (first known as sausage disease) C. botulinum doesnot grow in sausage today mainly due to nitrites added. Infant botulism 250 peryr., most associated with honey (due to unestablished microbial flora in G.I.

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    Tetanus (Lock Jaw) Clostridium tetani

    Gram (+), spore-forming, anaerobic rod neurotoxin acts on nerves, resulting in the

    inhibition of muscle relaxation tetanospasmin - spasms or Lock Jaw

    About 50 cases a yr. In U.S. World wide 1million per yr. (50% in newborns becausethey dress severed umbilical cord with soil,clay or cow dung) Tetanospasmin inhibits therelease of acetylcholine by interfering with

    activity of cholinesterase (enzyme thatnormally breaks down acetylcholine)

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    Diseases caused by Enterotoxins

    Cholera Vibrio cholerae Gram (-) comma

    shaped rods

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    Cholera toxin

    Converts ATP into cAMP causes cells to excrete Cl - ions and inhibits

    absorption of Na + ions Electrolyte imbalance

    H2O leaves by osmosis

    H2O Loss (Diarrhea)

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    Severe cases, 12 - 20 liters of liquid lost in a day

    Untreated cases - Mortality Rate about 50%

    Mortality may be reduced to about 1% administering fluids and electrolytes

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    EHEC(Enterohemorrhagic E. coli)

    E. coli (0157:H7) enterotoxin causes a hemolytic inflammation

    of the intestines results in bloody diarrhea

    Toxin alters the 60S ribosomal subunit inhibits Protein Synthesis Results in cell death lining of intestine is shed Bloody Diarrhea (Dysentary)

    H Hauch (film) seen ongrowth media if bacteria aremotile FLAGELLAO Ohne Hauch (without film)no flagella CELL WALLK Kapsel

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    Endotoxins - part of the Gram (-) Bacterialcell wall

    LPS (Lipopolysaccharides) O Antigen Lipid A

    Lipid A - Toxin portion of the LPS responsible for Fever that is associated with

    many Gram (-) Bacterial infections Gram (- ) cells are digested endotoxins are

    released - fever Antibiotics

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    Just Checking Differentiate bacteria, viruses, fungi, protozoa, and

    parasites of medical importance based on fundamentalfeatures and characteristics. (CILO1)

    Compare the fundamental features of selectedpharmaceutically important microorganisms. (CILO1)

    Determine the extent of occurrence of infectious diseasesand the severity of pathogenicity caused bymicroorganisms. (CILO3)

    Analyze the effect of microbial biofilms on the populationshealth. (CILO3)

    Recommend measures for the improvement of routineadministration of vaccines as well as vaccines forindividuals in special risk categories. (CILO3)

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    Please see

    http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/

    http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/http://www.authorstream.com/Presentation/mrlnpharma-624876-pharmaceutical-significance-of-microbes/
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    Chapter Completion Differentiate bacteria, viruses, fungi, protozoa, and

    parasites of medical importance based on fundamentalfeatures and characteristics. (CILO1)

    Compare the fundamental features of selectedpharmaceutically important microorganisms. (CILO1)

    Determine the extent of occurrence of infectious diseasesand the severity of pathogenicity caused bymicroorganisms. (CILO3)

    Analyze the effect of microbial biofilms on the populationshealth. (CILO3)

    Recommend measures for the improvement of routineadministration of vaccines as well as vaccines forindividuals in special risk categories. (CILO3)


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