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1Microbes and diseases: what to study-1
• 1. Causative microbe: name, morphology (shape, size, Gram stain, etc.), physiology (aerobe, anaerobe, etc) and some info on classification (what's it related to?)
• 2. Pathogenesis and clinical disease: what disease does it cause (signs and symptoms) and how does it do it (capsule, toxins..)?
• 3. Transmission and epidemiology: how do you get the disease?
2Microbes and diseases: what to study-2
• 4. Diagnosis: How does the lab usually identify the causative agent?
• 5. Treatment: antibiotics prescribed (or not- no cell wall, no penicillin) or other treatment (oral rehydration therapy for cholera).
• 6. Prevention and control (stop the spread; condoms, kill urban rats..)
3Staphylococcus: G+ coccus
• S. aureus and S. epidermidis.– 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– Food poisoning, skin diseases (impetigo, folliculitis,
furuncles & carbuncles, scalded skin syndrome), systemic diseases (TSS, bacteremia, heart, lung, and bone infections)
– Diseases spread by fomites and direct contact.
4Characteristics of S. aureus infections
tray.dermatology.uiowa.edu/ DIB/SSSS-002.htm www.omv.lu.se/.../ rorelse/popup/01d1x.htm
5S. aureus virulence factors & Rx
• Coagulase, triggers blood clotting.
• Capsules, beta-lactamases (destroy penicillins)
• 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).
http://www.biology4kids.com/extras/dtop_micro/7821_580.jpg
6Streptococci: G+ cocci
• Genera: Streptococcus and Enterococcus• Aerotolerant anaerobes, catalase negative
– Grow in chains, pairs– Strep: Lancefield groups, viridans, S. pneumoniae
• Group A strep: S. pyogenes– Pharyngitis, scarlet fever, pyoderma, erysipelas,
TSS, necrotizing fasciitis– Sequelae: rheumatic fever and glomerulonephritis
http://genome.microbio.uab.edu/strep/info/strep5.gif
7Characteristics of Streptococcal infections
http://euclid.dne.wvfibernet.net/~jvg/Bio208/resp_pix/scarlet-fever.jpg
http://textbookofbacteriology.net/vvpath.jpeg
8Virulence factors, etc.
• S. pyogenes (“pus-producing”)– M protein and capsule: avoids phagocytosis– Streptokinase, streptolysins for escape & attack– Pyrogenic erythrotoxins (SPEs)
• at least 3 different types• Cause scarlet fever: fever, rash; toxic shock
– Beta hemolytic on blood agar
• Viridans group: greenish alpha hemolysis– Common in throat, mouth, but can be opportunists– S. mutans associated w/ dental caries
9Clostridium: 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
10More 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
11Opposing 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.
12Function 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
13More 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• DPT, Toxoid vaccine • Booster: DT (with diphtheria toxoid)• No natural immunity: you would die first.
14Mycobacterium: G+ rods
• Many non-pathogenic species, most disease: M. tuberculosis and M. leprae– Mycolic acids as part of complex cell wall
• Protects against desiccation• Protects against destruction by phagocytes• Requires acid-fast staining
– Generally grow very slowly (chronic illnesses)– Can grow intracellularly
15Acid Fast stain of Mycobacteria
http://www.md.huji.ac.il/mirror/webpath/AIDS071.jpg
16M. tuberculosis
• Causes disease tuberculosis, mostly lung dis.
• Disease: cells enter lungs, infect macrophages– Macrophages not activated, can’t kill invader– Cell mediated immunity fights back, walls off
infection; forms tubercle (caseous necrosis occurs)– Disease remains controlled, cured, or returns
• Disseminated TB: spreads thru body
• Worldwide problem; lowered immunity=risk– Skin test, chest x-ray, drug treatment, vaccine?
17M. leprae
• Cause of Hansen’s disease, aka leprosy• Slow growing, likes it cool; armadillos as model• Grows in peripheral nerve and skin cells
– Numbness is characteristic of disease• Tuberculoid vs. lepromatous leprosy
– Mild, severe, respectively, depending on cell mediated immune response.
– Numbness vs tissue destruction• Spread mostly by direct contact• Treatable with antibiotics, but long term
18Gram negative rods and cocci
• Endotoxin: Lipid A, the superantigen – Part of LPS of the Gram negative outer membrane– Causes an over-stimulation of macrophages with
production of various cytokines– Fever, vasodilation, inflammation, shock, and
disseminated intravascular coagulation
• While Gram negative pathogens can have other virulence factors (capsules, fimbriae, exotoxins), all have endotoxin and are thus dangerous.
19Enterobacteriaceae: Gram negative rods
• Gram negative, small rods, facultatively anaerobic, oxidase negative; found in soil, water, and GI tracts– some strictly pathogens, others opportunists– Coliforms (ferment lactose) and non-coliforms
• Virulence factors– Endotoxin, capsules, fimbriae, exotoxins, others.
• Enteric bacteria identified by biochemical tests– Selective/differential media, IMViC tests, etc.– Strains identified by serological techniques
20Serology and enteric bacteria
• Because enteric bacteria are very closely related to each other, differentiation requires serology– Use of antibodies to identify particular antigenic
molecules on cell surfaces– O antigen: repeating sugar group on LPS– H antigen: flagellar protein– K antigen: capsule antigen around cell.– Example: E. coli O157:H7 describes particular serotype
which happens to also produce a dangerous exotoxin.
21
http://www.ratsteachmicro.com/Assets/Enterobacteriaceae/Enterobact_diagram2.gif
22E. 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.
23Truly 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• Importance of clean water and sewage treatment.• http://www.newsday.com/community/guide/lihistory/ny-history-hs702a,0,6698943.story
24Truly 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.
25Truly pathogenic enterics-3• Yersinia: Y pestis is cause of plague, other species
cause food-borne infections• Plague: 3 cycles: sylvan, urban, and human
– endemic in sylvan cycle; mixing of woodland and urban rodents brings urban cycle, fleas jump from dying rats to humans.
– Infection leads to large swollen lymph nodes: buboes• Bubonic plague, with high fever.• Septicemic plague: with DIC, bruising (black death)
– Raises mortality from75% to near 100%• Pneumonic: coughed out and spread human to human
– 100% mortality
26The S.F. earthquake and plague
http://library.thinkquest.org/03oct/00904/images/sanf.jpg http://www.cdc.gov/ncidod/dvbid/plague/plagwest.htm
27Other Gram - rods
• Francisella: F. tularensis, cause of tularemia– Also called rabbit fever, tick fever, deerfly fever, etc.– Most cases in US in Arkansas/Missouri Ozarks– Survives phagocytosis, lives intracellularly– Present in many animals, transferred to humans by
vector, ingestion, direct contact, inhalation– Chills, fever, malaise, swollen nodes
http://er1.org/docs/photos/Tularemia/Amblyomma%20Americanum%20(lone%20star%20tick).jpg
http://mercury.bio.uaf.edu/~george_happ/Francisella.jpg
28Other Gram – rods-2
• Legionella: L. pneumophila and several others– Fastidious in culture, requires special media– Very common in aquatic environments: ponds, cooling
towers, hotwater heaters, showers.– Grows normally in amoebae, so also grows in phagocytes– Most dangerous as opportunistic pneumonia, inhalation– Mild form of disease: ‘pontiac fever’
www.angelfire.com/.../ bicentennial.html
29Chlamydia
• Very small, obligate intracellular parasites– Cell and outer membrane, but no peptidoglycan
• Spread directly rather than by vectors
• Two stage life cycle– Elementary body: tiny (0.2-0.4 µm) and inert
• Spore-like: dormant and resistant• Infectious: form that moves between cells
– Reticulate body: 0.6-1.5 µm, metabolically active, reproduce inside host cells
30Chlamydial diseases
• C. trachomatis: infects cells of mucous membranes, conjunctiva. Mostly eye & STD– Infection kills cells, stimulates inflammation which
also causes cell destruction
• Trachoma- leading cause of non-traumatic blindness. Caused by certain strains.– Infection of conjunctiva causes scarring, turning in
on eyelashes which scratch cornea.– Scarred cornea, with ingrown blood vessels,
obscure vision.– STD strains can also infect eyes, self-inoculation.
31Sexually transmitted Chlamydial disease
• Non-gonococcal urethritis, about 50% of cases• Chlamydia infections are the most common STD, but
even more are infected and asymptomatic– 85% of women asymptomatic; others can develop
PID; scarring of uterine tubes can lead to sterility, ectopic pregnancy.
• Eye infections of newborns prevented with antibiotic drops.– Also protects against N. gonorrhoeae
32Gram 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
33Campylobacter
• 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– Gram neg. curved rod
http://www.shef.ac.uk/staff/newsletter/vol23no10/images/campylobacter.gif
34Helicobacter 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