Bacterial Pathogenesis - RIT - People - Home by yurtgc548

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									         NO Clicker questions at start of today’s class
May be a BONUS Clicker question during discussion of next topic




 Start of Exam 3 Material
                              Biosynthesis
• Use energy created (ATP) to produce structural and functional molecules
                                 Biosynthesis
•   Carbohydrates
•   Store excess glucose as glycogen
•   Form bonds between peptidoglycan sugars
•   Produce glucose (glycolysis going backwards)
•   Produce pentoses for DNA synthesis
                Biosynthesis
• Amino acids
                             Biosynthesis
• Nucleotides (for DNA synthesis)
• e.g., purines
                             Biosynthesis
• Fatty acids (for lipids)
      Next Topic
Bacterial Pathogenesis
                            Bacterial Pathogenesis
      Todar's Online Textbook of Bacteriology: Bacterial Pathogens of Humans

• Food and water (contaminated & untreated)
    – E. coli O157:H7
        – Undercooked ground beef & unpasteurized fruit drinks (e.g., cider)
    – Clostridium botulinum spores
        – Improperly prepared canned foods (e.g., beans)
    – Poultry (undercooked)
       – Salmonella
       – Salmonella enteriditis (undercooked eggs)

    Untreated water sources
        – Vibrio cholerae (cholera)
        – Shigella dysenteriae (bacterial dysentery)


• Aerosols (coughing and sneezing)
    – Mycobacterium tuberculosis (tuberculosis)
Bonus Clicker question. We used another species of
Mycobacterium in lab (M. smegmatis) for which one of the
following procedures? The result of this procedure is often very
useful in identifying members of the genus, Mycobacterium.

5 points for correct answer; 2 points for incorrect answer


• A. gram stain

• B. spore stain

• C. capsule stain

• D. acid-fast stain
• Transmission of human pathogens (a few examples)

• Insects (microorganisms are most often protozoan pathogens)
    – Plasmodium vivax (malaria)
    – World’s first malaria vaccine works in major trials
    – A Vaccine for Malaria (New England Journal of Medicine)


• Animals
    – Rabies (virus)
    – Yersinis pestis (bubonic plague) – rodents (fleas bite rodents)


• STDs
    – HIV (virus)
    – Neisseria gonorrhoeae (gonorrhea)
    – Treponema pallidum (syphilis)
                    Normal Flora – no need to “transmit”
•   Cause diseases when "relocated" and/or body conditions change

•   Streptococcus pneumoniae (moves from upper to lower respiratory tract)

•   Staphylococcus aureus (moves from nasal passage to skin and other sites)

•   Clostridium difficile (colon - use of antibiotics)
•   Exam 2 on front table grouped by first letter of last name/surname
•   Pick up ONLY your own exam
•   Your exam 2 score circled in red on 2nd page
•   Exam 2 class average = 39.1/50
•   Will address two ambiguous questions using Clickers
•   No other Clicker questions in today’s class


• Week 6 one-page data sheet is attached to back of Exam 2. Four points possible.
  If you earned less than four points, you can download a new copy of the data
  sheet (link from homepage), print it out and respond only to the observations or
  interpretations that have resulted points deducted. Staple new sheet (with
  corrections, additions, etc.) to original sheet (remove from back of exam) and
  submit both in class on Wednesday (no other submission will be accepted).
  Resubmitted data sheets will be reviewed and rescored (if responses have fully
  addressed the point deductions).
7. There are many examples of successful toxoid vaccines that take advantage of the
A-B structure/function of a bacterial exotoxin. For example, one toxoid vaccine, if
administered every 8-10 years maintains protection from a neurotoxin that can cause
extreme muscle contraction (the opposite of muscle paralysis). This exotoxin is
secreted by an obligate anaerobic, spore-forming, often club-shaped (but not
spherical-shaped) bacterium. Given this information, the toxoid vaccine being
described is likely one that provides protection from which one of the following
diseases?


• A. botulism

• B. tetanus

• C. meningitis caused by a meningococcus

• D. malaria
                            Botulism neurotoxin
•   Block synaptic signal (i.e., blocks acetylcholine release)
•   No nerve signal to muscles -> no muscle movement (paralysis)
•   Affects all muscles (voluntary and involuntary)
•   Heart, lungs, skeletal…………
•   Permanent nerve damage
•   Death can occur quite rapidly
7. There are many examples of successful toxoid vaccines that take advantage of the
A-B structure/function of a bacterial exotoxin. For example, one toxoid vaccine, if
administered every 8-10 years maintains protection from a neurotoxin that can cause
extreme muscle contraction (the opposite of muscle paralysis). This exotoxin is
secreted by an obligate anaerobic, spore-forming, often club-shaped (but not
spherical-shaped) bacterium. Given this information, the toxoid vaccine being
described is likely one that provides protection from which one of the following
diseases?


• A. botulism

• B. tetanus

• C. meningitis caused by a meningococcus

• D. malaria
18. Substrate-level phosphorylation would produce the energy source needed to carry
out the ABC transport mechanism. During which TWO of the following metabolic
pathways is this type of energy source produced in this manner (substrate-level
phosphorylation)? (Select TWO answers that are correct)



• A. Kreb’s cycle

• B. reduction of pyruvic acid (pyruvate) to lactic acid (lactate)

• C. electron transport system pathway

• D. Embden-Meyerhoff pathway
Kreb’s cycle
                                 ATP production continued
• Oxidative phosphorylation
•   ATP produced at the end of an electron transport system (ETS)
•   ETS generates proton motive force (PMF) - http://www.microbelibrary.org/images/Tterry/anim/ETSbact.html
•   PMF used to produce ATP (ATP synthase) - http://www.microbelibrary.org/images/Tterry/anim/ATPsynthbact.html
     – And other important activities, e.g., flagella movement, simple transport
18. Substrate-level phosphorylation would produce the energy source needed to carry
out the ABC transport mechanism. During which TWO of the following metabolic
pathways is this type of energy source produced in this manner (substrate-level
phosphorylation)? (Select TWO answers that are correct)


• Select ONE of the answers below

• A. Kreb’s cycle

• B. reduction of pyruvic acid (pyruvate) to lactic acid (lactate)

• C. electron transport system pathway

• D. Embden-Meyerhoff pathway (also called glycolysis)
18. Substrate-level phosphorylation would produce the energy source needed to carry
out the ABC transport mechanism. During which TWO of the following metabolic
pathways is this type of energy source produced in this manner (substrate-level
phosphorylation)? (Select TWO answers that are correct)


• Select a different ONE of the answers below

• A. Kreb’s cycle

• B. reduction of pyruvic acid (pyruvate) to lactic acid (lactate)

• C. electron transport system pathway

• D. Embden-Meyerhoff pathway (also called glycolysis)
• Week 6 one-page data sheet is attached to back of Exam 2. Four
  points possible. If you earned less than four points, you can
  download a new copy of the data sheet (link from homepage), print
  it out and respond only to the observations or interpretations that
  have resulted points deducted. Staple new sheet (with corrections,
  additions, etc.) to original sheet (remove from back of exam) and
  submit both in class on Wednesday (no other submission will be
  accepted). Resubmitted data sheets will be reviewed and rescored
  (if responses have fully addressed the point deductions)
            How are you doing so far in Intro Micro?
• Final Calculated Grade is no longer a valid way to determine this

• BEST way is to use points earned to date (including lab bonus)

• 1. Use only 50 of your total Clicker points earned to date (points over will
  be used later to adjust lowest exam score)

• 2. Divide total number of points earned (with max of 50 for Clicker) by 243
  (total points that can be earned to date – assigns 3 points to lab 7)

• 3. Total earned to date/243 = % performance to date
    –   90% or above – performing at “A” level
    –   80-89.9% - performing at a “B” level
    –   70-79.9% - performing at a “C” level
    –   60-69.9% - performing at a “D” level
START of October 24 discussion
                    Normal Flora – no need to “transmit”
•   Cause diseases when "relocated" and/or body conditions change

•   Streptococcus pneumoniae (moves from upper to lower respiratory tract)

•   Staphylococcus aureus (moves from nasal passage to skin and other sites)

•   Clostridium difficile (colon - use of antibiotics)

•   Streptococcus mutans (if oral hygiene is substandard)

•   Streptococcus pyogenes (strep throat and rheumatic fever)

•   Propionibacterium acne (high lipid/oils on skin)
            Other ways to oxidize NADH -> NAD (for reuse)
•   Wide variety of other end products are produced depending on what is happening
•   Still starts with pyruvic acid
                    Normal Flora – no need to “transmit”
•   Cause diseases when "relocated" and/or body conditions change

•   Streptococcus pneumoniae (moves from upper to lower respiratory tract)

•   Staphylococcus aureus (moves from nasal passage to skin and other sites)

•   Clostridium difficile (colon - use of antibiotics)

•   Streptococcus mutans (if oral hygiene is substandard)

•   Streptococcus pyogenes (strep throat and rheumatic fever)

•   Propionibacterium acne (high lipid/oils on skin)

•   Helicobacter pylori (90-95% of peptic ulcers)
               THREE Clicker questions at the start of class
•   1. The proper and rapid use of an effective broad-spectrum antibiotic to treat a
    bacterial infection (e.g., strep throat) can actually cause problems with resident
    normal flora leading to which one of the following pathologies caused by an
    opportunistic pathogen that is also an anaerobic bacterium? Hint: this bacterium
    can often be effectively treated by metronidazole

•   2. Which one of the following microorganisms secretes large quantities of dextran
    (a glucose polymer that is an example of an adherent “biofilm”), can produce
    organic acids under anaerobic conditions, is gram-positive and spherical-shaped, is
    often an oral normal flora, and grows well on Mitis-Salivarius agar?

•   3. Polar flagella, spirillum-shape, neutralizes acidic pH, urease positive, ulcers are
    all terms that apply to which one of the following microorganisms?



•   Turn in Week 6 data sheet (new one with corrections/additions, etc. stapled to
    your original one) on the front table. Will be rescored and returned in class on
    Monday. All week 7 data sheets will also be returned in class on Monday.
The proper and rapid use of an effective broad-spectrum antibiotic to treat a
bacterial infection (e.g., strep throat) can actually cause problems with
resident normal flora leading to which one of the following pathologies
caused by an opportunistic pathogen that is also an anaerobic bacterium?
Hint: this bacterium can often be effectively treated by metronidazole.


• A. damage to the lining of the large intestine (colon)


                                                       Clostridium difficile
• B. rheumatic fever



• C. syphilis



• D. candidiasis
Which one of the following microorganisms secretes large quantities of
dextran (a glucose polymer that is an example of an adherent “biofilm”), can
produce organic acids under anaerobic conditions, is gram-positive and
spherical-shaped, is often an oral normal flora, and grows well on Mitis-
Salivarius agar?

• A. Streptococcus mutans



• B. Streptococcus pyogenes



• C. Lactobacillus acidophilus



• D. Staphylococcus epidermidis
Polar flagella, spirillum-shape, neutralizes acidic pH, urease positive, ulcers
are all terms that apply to which one of the following microorganisms?


• A. Corynebacterium diphtheria



• B. Rhodospirillum rubrum



• C. Helicobacter pylori



• D. Neisseria meningitides
START of October 26 discussion
                       More examples of bacterial pathogens
    Pathogenic Microbiology - The Study of Disease-Causing Bacteria: List of Bacterial Pathogens

• List of Bacterial Pathogens
     http://www.life.umd.edu/classroom/bsci424/PathogenDescriptions/PathogenList.htm
• Infectious Diseases Sorted by Etiological Agent
•    http://classes.midlandstech.edu/carterp/Courses/bio225/InfectiousDiseases_all_print.htm


• Typhus – Rickettsia typhi
      • Obligate intracellular parasite (bacterium)
• Typhoid – Salmonella typhi
• Meningitis
      • Viral
      • Bacterial
          • Neisseria meningitidis (meningococcal vaccine)
          • Streptococcus pneumoniae (Prevnar vaccine)
          • Haemophilus influenzae type b (Hib vaccine)
                 More examples of bacterial pathogens
• Whooping cough – Bordetella pertussis
• Staphylococcal aureus infections
    – antibiotic resistance - penicillin, methicillin, vancomycin, and …….
• Toxic shock syndrome (TSS)
    – Staphylococcus and Streptococcus species
• “Pneumonia”
    –   Streptococcus pneumoniae
    –   Klebsiella pneumoniae
    –   Chlamydia pneumoniae
    –   Mycoplasma pneumoniae
    –   Haemophilus influenzae
    –   Mycobacterium tuberculosis
                TWO Clicker questions at the start of class
•   1. The most common cause of bacterial spinal meningitis in the adult college
    population is found as a member of the normal flora of the upper respiratory tract
    of a approximately 20% of this population. This bacterium (which is a gram-
    negative diplococcus) is which one of the following?

•   2. Although much rarer now than in the recent past, toxic shock syndrome (TSS)
    still occurs in women who use super absorbent tampons and do not change them
    on a frequent basis. This creates “ideal” conditions for heavy growth of a
    bacterium that is actually a normal flora of the vagina, with a resultant production
    of copious amounts of several exotoxins that, collectively, are responsible for the
    symptoms of TSS. Until recently, this bacterium was quite easily treated with the
    antibiotic, methicillin. It is a gram-positive, coagulase-positive, catalase-positive
    bacterium that produces a bright yellow color when grown on Mannitol Salt
    agar. This bacterium is which one of the following?

•   ALL scoring of labs, resubmitted Week 6 data sheets, Week 7 data sheets, etc. will
    take place sometime this weekend

•   Exam 3 – two weeks from today
The most common cause of bacterial spinal meningitis in the adult college population
is found as a member of the normal flora of the upper respiratory tract of a
approximately 20% of this population. This bacterium (which is a gram-negative
diplococcus) is which one of the following?


• A. Streptococcus pneumoniae (formerly called Diplococcus pneumoniae)



• B. Haemophilus influenzae type B



• C. Staphylococcus aureus



• D. Neisseria meningitidis (often commonly called meningococcus)
Although much rarer now than in the recent past, toxic shock syndrome (TSS) still occurs in
women who use super absorbent tampons and do not change them on a frequent basis. This
creates “ideal” conditions for heavy growth of a bacterium that is actually a normal flora of the
vagina, with a resultant production of copious amounts of several exotoxins that, collectively, are
responsible for the symptoms of TSS. Until recently, this bacterium was quite easily treated with
the antibiotic, methicillin. It is a gram-positive, coagulase-positive, catalase-positive bacterium
that produces a bright yellow color when grown on Mannitol Salt agar. This bacterium is which
one of the following?

• A. Group A, beta hemolytic Streptococcus pyogenes



• B. Candida albicans



• C. Streptococcus agalactiae (a group D strep that can also harm newborn
  infants)

• D. Staphylococcus aureus
BONUS Clicker Question

Group A, beta-hemolytic, gram-positive, rheumatic fever, protein capsule all
describe which one of the following bacteria?


• A. Streptococcus pneumoniae



• B. Mycobacterium smegmatis



• C. Propionibacterium acne



• D. Streptococcus pyogenes
START of October 28 discussion
       Emerging and re-emerging infectious diseases – why?

• Tuberculosis (Mycobacterium tuberculosis) – antibiotic resistance

• Staphylococcus aureus – vancomycin resistance

• Polio (virus disease) – decrease in, or no, use of polio vaccines

• Cholera (Vibrio cholerae) – declining sanitary conditions

• Campylobacter jejuni food contamination – reason unknown

• Whooping cough (Bordetella pertussis) – vaccine effectiveness may have
  “worn off” (“aP” portion of DaPT vaccine)

• Measles (virus) – initial vaccine (“M” part of MMR) may not have been
  effective for persons now of college age
                          Bacterial virulence factors
Todar's Online Textbook of Bacteriology: Mechanisms of Bacterial Pathogenicity MICROBIOLOGY
           101/102 INTERNET TEXT:: CHAPTER XIII: HOW MICROBES CAUSE DISEASE

• Anything that contributes to pathogenicity
• Can be a single virulence factor
• Some bacteria have a very wide variety of virulence factors
              Bacterial virulence factors – some examples
• Exotoxins (secreted enzymes and waste products)
• Cytolytic exotoxins
    – Destroy red blood cells or nucleated cells
    – Hemolysins (Streptococcus pyogenes)
    – Leukocydins (Streptococcus pyogenes – streptolysin)
• Invasive enzymes
    – Staphylococcus aureus – hyaluronidase
    – Clostridium perfringens – collagenase
• Break down clots (to release bacteria)
    – streptokinase, staphylokinase
• Form clots (to protect bacteria from body defenses)
    – coagulase (Staphylococcus aureus)
• A-B exotoxins
    – Corynebacterium diphtheriae (diphtheria)
START of October 31 discussion
                         A-B exotoxins (continued)
• Neurotoxins
   – Botulism (Clostridium botulinum)
   – Tetanus (Clostridium tetanus)
                    Prevention and treatment of tetanus

•   Prevention
•   Tetanus toxoid vaccine (toxin is an A-B exotoxin)
•   Vaccine is effective for 8-10 years
•   Requires “booster” to maintain protection

• Treatment - Physician’s response to various scenarios regarding possible
  exposure to tetanus toxin
     – Patient knows her immunization history and has received a tetanus “shot” (toxoid) in the
       past 8 years
     – Patient does not know her immunization history or is not sure about any tetanus “shot”
     – Patient knows her immunization history and has not received a tetanus vaccine (or
       booster) in the past 8-10 years
     Cholera pathology is caused by a Vibrio cholerae enterotoxin
• Exotoxins that affect the intestinal tract
• Bacterium adheres to endothelial cells
    – (via fimbriae)
• Secretes A-B enterotoxin
    – Two distinct functional parts
    – B attaches to membrane GM1 ganglioside
    – A enters - dramatically increases cAMP production
• High concentration of ions pumped into in lumen
    – Water flows out of tissues in attempt to
      create equilibrium solute concentration
• Quantity of water loss from body can be huge
• Endotoxins
• Lipid A portion of gram-negative lipopolysccharides
• Stimulates overreaction of body’s phagocytic cells
    – normal body tissue is destroyed
    – excessive inflammation
• Difficult to make effective vaccine
                             Adherence mechanisms
                (where attachment is crucial to initiating pathology)
•   Fimbriae (already discussed)
•   Capsules (in addition to providing protection from phagocytosis)
     – Polysaccharide (Streptococcus pneumoniae, Klebsiella pneumoniae)
     – Protein (Streptococcus pyogenes)
•   Biofilms
     –   extracellular DNA, proteins, polysaccharides
     –   dextrans in the oral cavity (Streptococcus mutans)
     –   Neisseria gonorrhoeae
     –   Cystic Fibrosis - Pseudomonas aeruginosa
     –   medical catheters
     –   Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus
         viridans, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas
         aeruginosa
   Next Topic

Bacterial Genetics

								
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