Current Diseases

• Staphylococcus

• Clostridia

• Food-borne bacteria

• Malaria

• Influenza

• Common cold

• HIV

• HPV

1

2Staphylococcus: 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.

3Characteristics of S. aureus infections

tray.dermatology.uiowa.edu/ DIB/SSSS-002.htm www.omv.lu.se/.../ rorelse/popup/01d1x.htm

4S. aureus virulence factors & Rx

• Capsules, hyaluronidase, staphylokinase, beta-lactamases (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

5Clostridium: G+ rods

• 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

6More clostridia

• 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

7Opposing muscle groups

http://upload.wikimedia.org/wikipedia/sv/thumb/d/dd/185px-Muscles_biceps_triceps.jpg

When biceps contracts, triceps relaxes.

When triceps contracts, biceps relaxes.

Excitatory neurons send signal to contract, inhibitory neurons send signal to NOT contract.

8Function of nerves

http://www.people.virginia.edu/~dp5m/phys_304/figures/motor_unit.jpg

http://upload.wikimedia.org/wikipedia/fr/thumb/e/e4/200px-Synapse.png

9More 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.

10Gram negative rods

• Enteric bacteria– Gram negative, rod shaped, facultative anaerobes, non-

spore 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.

11

http://www.ratsteachmicro.com/Assets/Enterobacteriaceae/Enterobact_diagram2.gif

12E. coli: friend or foe?

• 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.

13Truly pathogenic enterics

• 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.

14Truly pathogenic enterics-2

• 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.

15Gram negative curved rods

• 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

16Campylobacter

• 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/images/campylobacter.gif

17Helicobacter 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

18Rogue’s gallery-4

• 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

Intracellular plasmodia

www.sirinet.net/ ~jgjohnso/plasmodium.html

Yearly: 300-500 million new cases;

1 million deaths.

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Life cycle of Plasmodium

www.sirinet.net/ ~jgjohnso/plasmodium.html

20

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.

21Orthomyxovirus

• 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.

22View of flu

http://www.astrosurf.org/lombry/Bio/virus-influenza.jpg

http://www-micro.msb.le.ac.uk/3035/3035pics/flusection.jpg

23Nature 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

24Role of H and N spikes and host cell

polysaccharide

25influenza

• 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 $

26The Common cold

• 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

27HIV: Human Immunodeficiency Virus

• 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

28Disease process

• 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

29Prevention 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.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__hiv_replication.html

30HPV

• 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 (HPV-16) infections (50% of all cervical cancers)

31Gardasil

• 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.