Download Microbes and diseases: what to study-1

Current Diseases
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Staphylococcus
Clostridia
Food-borne bacteria
Malaria
Influenza
Common cold
HIV
HPV
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Staphylococcus: G+ coccus
• S. aureus and S. epidermidis (and 21 others).
– S. aureus much worse, S. epi an opportunist.
– Sturdy, salt tolerant, fac anaerobes; clusters
– S. epidermidis common on skin, S. aureus less.
• Diseases of S. aureus
– Invasive: skin diseases (rashes, abscesses)
• systemic diseases (bacteremia, organ and bone
infections)
– Toxin: toxic shock syndrome, scalded skin
syndrome, food poisoning
– Diseases spread by fomites and direct contact.
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Characteristics of S. aureus infections
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tray.dermatology.uiowa.edu/ DIB/SSSS-002.htm www.omv.lu.se/.../ rorelse/popup/01d1x.htm
S. aureus virulence factors & Rx
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• Capsules, hyaluronidase, staphylokinase, betalactamases (destroy penicillins), leukocidins
• Toxins: various, including TSS toxin, exfoliatin,
and enterotoxins (heat stable)
• 95% resistant to penicillin, but now many
resistant to methicillin, oxacillin. Treatment
usually clindamycin (oral) or vancomycin (IV).
• S.aureus carried by 30-40%
– Well adapted to life with humans
• http://www.textbookofbacteriology.net/staph.html
Clostridium: G+ rods
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• Strict anaerobes! Endospore formers. Toxigenic
– Common in soil, sewage animal GI tracts
– Produce neurotoxins, enterotoxins, histolytic toxins
• Four important species: C. perfringens, C.
botulinum, C. tetani, and C. difficile.
• C. perfringens
– Food poisoning: cramps and diarrhea
– From injury: myonecrosis to gas gangrene
• Fermentation in tissues, killing of tissues and
spread of cells into anaerobic areas.
• Oxygen treatment, debridement, amputation
More clostridia
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• C. difficile: normal GI microbiota
– Cause of pseudomembranous colitis, resulting from
overgrowth following broad spectrum antibiotics
• Damage to GI wall can lead to serious illness
– Nosocomial infection, easily transmitted
• C.botulinum: cause of botulism
– Usually acquired by ingestion: intoxication
• Food borne, infant (no honey), wound
– Produces neurotoxin, inhibits acetylcholine release
• Flaccid paralysis; Botox: deadly poison / beauty
– Mouse bioassay; administer antitoxin
Opposing muscle groups
When biceps contracts,
triceps relaxes.
When triceps contracts,
biceps relaxes.
Excitatory neurons send
signal to contract, inhibitory
neurons send signal to NOT
contract.
http://upload.wikimedia.org/wikipedia/sv/thumb/d/dd/185px-Muscles_biceps_triceps.jpg
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Function of nerves
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http://upload.wikimedia.org/wikipedia/fr/thu
mb/e/e4/200px-Synapse.png
http://www.people.virginia.edu/~dp5m/phys_304/figures/motor_unit.jpg
More clostridia-2
• C. tetani: cause of tetanus
– Growth in anaerobic wounds, makes tetanus toxin
– Toxin prevents action of inhibitory neurons
• Opposing muscle pairs both contract
• Spastic paralysis, leading to death.
– Recommendation is booster shot every 10 years
• Toxoid vaccine, with diphtheria toxoid
• No natural immunity: you would die first.
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Gram negative rods
• Enteric bacteria
– Gram negative, rod shaped, facultative anaerobes, nonspore forming, oxidase negative; Proteobacteria
– Possess endotoxin
– Medically significant but taxonomically similar
– Distinguished with biochemical tests and serological
tests.
– Serological tests: using specific antibodies (as found in
serum) to distinguish small differences in surface
molecules of bacteria.
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http://www.ratsteachmicro.com/Assets/Enterobacteriaceae/Enterobact_diagram2.gif
E. coli: friend or foe?
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• E. coli: cause of 90% of urinary tract infections
– Most strains common to GI tract, not harmful there.
– Strains have fimbriae needed for attachment
– Proanthocyanidins in cranberry juice interfere
• E. coli: common cause of diarrhea
– Many strains possess genes (some on plasmids) that code
for additional virulence factors like exotoxins which
cause disease
• E. coli O157:H7: possesses shiga toxin; strain causes
hemolytic uremia syndrome, damages kidneys.
• E coli strains classified as EHEC, EIEC, EPEC, etc.
– Enterohemorrhagic, enteroinvasive, etc.
Truly pathogenic enterics
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• Salmonella: species so closely related that they are
really all S. enterica. But medically, species epithets
still used: S. typhi and others. Divided serologically.
– Present in eggs, poultry, on animals such as reptiles
– Large dose results in food poisoning; diarrhea, fever, etc.
– Cells phagocytized by intestinal lining cells, kill cells
causing symptoms, may pass through into blood.
– S. typhi: typhoid fever. Spread through body
• Gall bladder as reservoir; Typhoid Mary
– http://www.pbs.org/wgbh/nova/typhoid/
• Importance of clean water and sewage treatment.
Truly pathogenic enterics-2
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• Shigella: especially S. sonnei (most common) and S.
dysenteriae (most serious); cause shigellosis.
– Food, flies, fingers, feces, fomites: very small infectious
dose, personal hygiene important in prevention.
– Infection of intestinal lining damaged, cells pass directly
from cell to cell; cramps, diarrhea, bloody stools.
– S. dysenteriae produces shiga toxin which inhibits
protein synthesis, increases damage.
– Most serious problem with diarrheal diseases in
general is dehydration.
Gram negative curved rods
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• Vibrio: comma shaped
– Like enteric but oxidase positive; polar flagella
– Halotolerant to halophilic, grow in estuarine and
marine environments
– V. cholerae: cause of cholera
• Toxin-mediated severe diarrhea
• Salt, fluid leave intestinal cells, patient dies of
dehydration.
• Oral rehydration therapy (ORT): water, salts, and
glucose, now saving lives.
• Causes pandemics that spread around the world
– Lack of adequate sewage treatment
Campylobacter
• Campylobacter jejuni: number one cause of
bacterial gastroenteritis; zoonotic
– More common than Salmonella and Shigella
combined for food borne disease.
– Most retail chickens are contaminated; improperly
cooked chicken and contaminated milk typical
vehicles.
– Low infectious dose
http://www.shef.ac.uk/staff/newsletter/vol23no10/image
s/campylobacter.gif
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Helicobacter pylori
• Cause of ulcers and gastritis
– 2005 Nobel Prize for Medicine or physiology to
Barry Marshall and J Robin Warren
– Unusual because it can live in stomach
– Produces urease enzyme
• Released ammonia neutralizes stomach acid,
irritates stomach lining.
• Basis for radioactive urease test.
– Correlated with stomach cancer.
http://s99.middlebury.edu/BI330A/STUDENTS/KASSIS/images/pylori1b.jpg
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Rogue’s gallery-4
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• Sporozoans
– Plasmodium: the cause of malaria, several species
• Involves mosquito, liver, red blood cells in a complex
life cycle.
• Features a synchronous bursting of RBCs with fever,
delerium, followed by rest and recovery, then cycle
• Number one cause of global mortality and morbidity
Yearly: 300-500
million new cases;
Intracellular plasmodia
1 million deaths.
www.sirinet.net/ ~jgjohnso/plasmodium.html
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Life cycle of
Plasmodium
www.sirinet.net/ ~jgjohnso/plasmodium.html
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In the poorest parts of the world, where effective window
screens are lacking, insecticide-treated bed nets are
arguably the most cost-effective way to prevent malaria
transmission. One bed net costs just $10 to buy and
deliver to individuals in need. One bed net can safely
last a family for about four years, thanks to a long-lasting
insecticide woven into the net fabric.
Orthomyxovirus
• Influenza: a serious respiratory disease
– Virus has a segmented genome
• 8 different RNA molecules
– Spikes: Hemagglutinin and Neuraminidase
• Major antigens recognized by immune system
• Antigenic drift and shift
– Drift: small mutations, making host susceptible
• Requires new vaccine each year
– Shift: major mixing of RNAs, whole new virus.
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View of flu
http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg
http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg
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Nature of influenza
• Attack on respiratory tract
– Kills ciliated epithelial cells, allows bacterial
infections.
– Release of interferon from cells causes symptoms
• H antigen (hemagglutinin) for attachment
– That it agglutinates RBCs is an artifact
• N antigen: neuraminidase
– Cuts of the sugar on the glycoprotein receptor
– Allows new virions to escape from cell without
getting stuck
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Role of H and N spikes and host cell
polysaccharide
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influenza
• Changes in H and N (antigenic shift)
– Mixing of viruses that infect birds, pigs, produce
new strains able to jump to humans.
– New antigenic type leaves population unprotected
– Numerous epidemics throughout history
• Flu of 1918-1919 killed 20 million
– Asia watched very carefully: bird flu?
• Flu vaccines made from deactivated viruses
– Slow process (vaccine made in eggs), so every
year correct strains are “guessed”.
– Cell culture would be quicker but more $
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The Common cold
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• Rhinoviruses have many serotypes
– Variants, caused by easy mutation of RNA
– Immune system can’t recognize all differences, but
some protection with age.
– Multiplies in narrow temperature range, nose/sinus
cooler than body temperature
• Other cold viruses
– Coronavirus (best known cousin causes SARS)
– Adenovirus (DNA virus), some serotypes cause GI
infections
HIV: Human Immunodeficiency Virus
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• Host range
– Main types of cells infected: T helper cells and
dendritic cells (including macrophages, microglia)
• Have CD4 and CCR5 glycoproteins on surface
• Infection process
– RNA is copied into cDNA by reverse transcriptase
– cDNA inserts into host chromosome
– New RNA made
– Protein precursor made, then processed; assembly
occurs
– Virions bud through cell membrane
Disease process
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• Chronic infection
– T cells continually made, continually destroyed
– Eventually, host loses
• AIDS diagnosis:
– Acquired Immuno Deficiency Syndrome
• CD4 cell count below 200/µl;
• opportunistic infections
• Examples of opportunistic “infections”
– Pneumocystis carinii pneumonia (PCP pneumonia)
– Kaposi’s sarcoma; Tuberculosis; several others
Prevention and Treatment
• Prevention is easy
– Practice monogamous sex, avoid shared needles
– HIV cannot be spread by casual contact, skeeters
• Drug treatment
– Nucleoside analogs such as AZT
– Protease inhibitors prevent processing of viral
proteins
Nifty animation at:
http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter24/animat
ion__hiv_replication.html
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HPV
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• Papilloma virus
– Cause of warts, in this case, genital warts
– Virus tricks cell into preparing for cell division
• Protein E7 binds to pRB
– Leads to greater susceptibility to cancer, particularly
cervical cancer (and penile and anal cancer)
• Especially those viral strains that aren’t good at
causing actual warts
• CDC researchers: estimated 20 million people in
the US have human papillomavirus type16 (HPV16) infections (50% of all cervical cancers)
Gardasil
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• New vaccine
– Protects against HPV types 16, 18, 6, and 11
– These biotypes account for 70% of cases of cervical
cancer and 90% of cases of genital warts.
– Vaccine: a recombinant vaccine w/ capsid proteins
• Estimate: 3,700 to die of cervical cancer in
2006
• Controversy: should it be mandatory?
– Religious right, big Pharmaceutical lobby, etc.