Transcript Microbes and diseases: what to study-1

Microbes and diseases: what to study-1
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?
Microbes 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..)
2
Staphylococcus: G+ coccus
3
• 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.
Characteristics of S. aureus infections
4
tray.dermatology.uiowa.edu/ DIB/SSSS-002.htm www.omv.lu.se/.../ rorelse/popup/01d1x.htm
S. aureus virulence factors & Rx
5
• 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
Streptococci: 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
6
Characteristics of Streptococcal infections
http://euclid.dne.wvfibernet.net/~jvg/Bio208/resp_pix/scarlet-fever.jpg
http://textbookofbacteriology.net/vvpath.jpeg
7
Virulence 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
8
Clostridium: G+ rods
9
• 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
10
• 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
11
Function of nerves
12
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
• DPT, Toxoid vaccine
• Booster: DT (with diphtheria toxoid)
• No natural immunity: you would die first.
13
Mycobacterium: 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
14
Acid Fast stain of Mycobacteria
http://www.md.huji.ac.il/mirror/webpath/AIDS071.jpg
15
M. tuberculosis
16
• 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?
M. 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
17
Gram negative rods and cocci
18
• 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.
Enterobacteriaceae: Gram negative rods
19
• 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
Serology and enteric bacteria
20
• 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_diagra
m2.gif
E. coli: friend or foe?
22
• 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
23
• 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/lihistor
y/ny-history-hs702a,0,6698943.story
Truly pathogenic enterics-2
24
• 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.
Truly pathogenic enterics-3
25
• 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
The S.F. earthquake and plague
http://library.thinkquest.org/03oct/00904/images/sanf.jpg
http://www.cdc.gov/ncidod/dvbid/plague/plagwest.htm
26
Other 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/Tularem
ia/Amblyomma%20Americanum%
20(lone%20star%20tick).jpg
http://mercury.bio.uaf.edu/
~george_happ/Francisella.
jpg
27
Other Gram – rods-2
28
• 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
Chlamydia
• 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
29
Chlamydial 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.
30
Sexually transmitted Chlamydial disease
31
• 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
Gram negative curved rods
32
• 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
– Gram neg. curved rod
http://www.shef.ac.uk/staff/newsletter/vol23no10/image
s/campylobacter.gif
33
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
34