Micro MCM unit 1 Flashcards
how genetic changes influence changes in infectious disease
changes in the gene sequence change virulence/pathogenicity, the host they can infect and antibiotic resistance
- syphilis and scarlet fever lose virulence gene
- mutation in flu caused spanish flu pandemic
- AIDS used to infect primates
- staphylococci and others are resistant to penicilin bc of natural selection
- HIV developing resistance to anitvirals
how changes in public health influence changes in infectious disease
clean water, clean air and vaccines make infections more rare
- clean water prevents cholera
- clean air prevents respiratory infections
- vaccines make MMR rare
- in all of these cases the organisms have not changed and will infect if precautions stop being taken
diseases of unknown etiology might be infectious
- recently found stomach ulcers and cervical cancer are infectious
- due to genes and gut microbes
- other possibly infectious conditions include obesity, stroke, heart attack, alzheimers, MS, diabetes
- you can transfer obesity in mice
bacterial structure
- genome made of DNA, no introns
- chromosomes are single, circular
- 70s ribosomes
- peptidoglycan cell wall, optional LPS, LOS envelope
- replicate by binary fission
- genome located in nucleoid
virus structure
- genome of DNA or RNA
- single, segmented chromosomes
- no ribosomes
- protein capsule on outside, optional outer lipid envelope
- replicates by invading bacteria; parasitic
- no particular genome location
eukaryotic structure
- genome made of DNA with introns
- multiple chromosomes
- 80s ribosomes
- replication by mitosis
- genome in the nucleus
bacterial cell size vs. animal cell size
bacterial cells are much smaller so animal cells are able to engulf
possible bacterial morphology under light microscope
cocci
bacilli
vibrio
spirochetes
Neiserria, e coli, pseudomonas, V cholerae, borrelia, treponema shape
Neisseria - diplococci e coli - bacilli pseudenomas - bacilli V cholerae- vibrio borrelia/lyme - spirochetes treponema/syphillus - spirochetes
bacterial structures with pathogenic significance
LPS - part of g- walls, an endotoxin, made of O antigen and lipid A. in g+ techoic acid is similar but less toxic
glycocalyx -
- slime layer - loose coating of polysaccharides that aid in attachment. form biofilms that are more resistant to antibiotics and hygiene tools because more diverse
- capsule - firm enclosure that helps with attachment and makes harder to engulf. can make vaccine targeting capsule (meningococcal capsule gives virulence)
- pili/fimbrae - for attachment. e coli cause UTI this way.
gram stain procedure
- fixation with heat
- crystall violet stain - purple
- iodine - makes crystal violet permanent for g+
- alcohol destain - for g-
- counterstain - safranin
g+ vs g-
- presence of LPS/LOS outside of cell wall in g- and thinner peptidoglycan cell wall
- only g+ make spores
additional bacterial structures for pathogenesis
- flagella - recognized as an antigen in humans
- ribosomes - target for antibiotics
- spores - resistant to antibiotics and genes
importance of exponential growth in pathogenesis and lab diagnosis
lots of nutrients make it very pathogenic
- can grow to take over the world in weeks
- but log phase does not last long
- identify by conditions they grow best in
fermentation vs. O2 based ATP generation
- O2 used electron transport chain, produces a lot of ATP. will be restricted to O2 rich areas of the body
- fermentation produces small amount of ATP. acid from fermentation can be used to identify. leave a lot of energy in waste that can be used by others later. these will grow in sealed cans
- facultative anaerobes can grow in almost anything (e coli)
- aerotolerant if have catalase or dismutase to detoxify O2
quorum sensing
change gene expression based on population density.
- allow conservation of energy and coordinated attack
- low density –> no inducer
- high density–> inducer.
- when theres enough inducer, there is a transcriptional activator that causes density dependent genes to be transcribed/expressed.
- used for making biofilms and virulence factors
dipicolinic acid
calcium chelator in spores
peptidoglycan structure and as drug target
- made of NAG and NAM with peptide cross-links and side chains
- target peptidoglycan because it is essential to bacterial cells but not to human cells.
- penicillin inhibits its synthesis, lysozyme cleaves it
how pathogens spread
- contact - direct, indirect, droplet
- airborne
- respiratory (vehicle and vectors)
chain of infection
- pathogen
- reservoir
- portal of exit
- means of transmission
- portal entry
- new host
strategies to prevent spread of pathogen
- hand hygiene
- PPE
- isolate
- sterilize
- housekeeping
- ventilation
- proper disposal
Airborne precautions
- mask and gloves and private, neg pressure room
- patient mask if leave room
- TB, chicken pox, shingles, measles, pandemic flu
droplet precautions
- coughing, sneezing, talking, procedure
- mask, gown, handwashing
- meningitis, seasonal flu, pertussis, mumps
contact precautions
- microbes spread by direct contact
- gown and alcohol based hand wash
- multi-drug resistant bacteria: MRSA, VRE, acinebacter, ESBL, rotavirus, scabies
contact plus precautions
- serious illness easily transmitted
- soap and water, not alcohol
- disinfect room with bleach
- C dif, diarrhea, norovirus, enteric infections (camp, e coli, shilgella, salmonella, crypto)
reverse isolation
mask, gloves, gown
-protect immunocompromised from other people
sterilization definition
destroy/eliminate all microbes by physical/chemical means
-not for living tissue
disinfection definition
eliminate many pathogens (not spores) on inanimate object
- 3 levels depending on how many microbes destroyed
- 3 levels depending on required strength
antisepsis
reduce microbes on living tissue internally, externally and on surgery tools
-doesnt kill spores and doesnt disinfect
potential for transmitting infectious agents on medical devices
- critical - enter normally sterile area of body. need to sterilize
- semicritical - in contact with mucous membranes or non-intact skin that should be free of microbes other than spores
- use a high level disinfect
- includes respiratory, anesthesia, endoscope, butt, throat - non-critical - for items on intact skin.
- use alc, halogens, phenolics, quants
- bedpans, bp cuff, crutches, computers
physical techniques used for sterilization
- steam/autoclave - effective and quick **most common
- dry heat - for petroleum based substances
- irradiation - single use medical supples
- gas - highly flammable
- plasma - high penetration; excite gases to disrupt metabolism
chemical sterilization techniques
- glutaraldehydes - hospital instruments
- hydrogen peroxide - releases O2 to produce radicals that damage DNA/protein
(6% for equipment, 30% sporicidal) - peracetic acid - mix of acetic and H2O2
- disrupts cell membrane
-clean water tower to prevent biofilm and carcass sanitation
promoter
where, when, what degree a gene is expressed
RNA pol
binds to promoter to initiate transcription and produce mRNA
operon
cluster of genes with related function controlled by 1 promoter
repressor
blocks expression
inducible expression
inducer/substrate binds to repressor to remove it fromo operon and allow expression
negative vs. positive regulation
- positive: usually repressed. need transcription factor to bind at promoter to initiate expression
- negative: product acts as repressor to prevent more of itself from being made
operator
regulates expression of operon and separates gene from promoter
ways to acquire new genes
mutations
- spontaneous
- chemical modifying
- physical agents
these often lead to antibiotic resistance
types of gene exchange in bacteria
- transformation
- conjugation
- transduction
transformation
DNA from dead bacteria gets taken up as chromosomal DNA or a plasmid
- could be incorporated by homologous recombination
- restriction enzymes often digest this DNA with different patterns or they get methylated and spliced out
conjugation
males are F+ and transfer F factor and surrounding DNA to F- females. the F factor has sex pili and genes for conjugation process
-often transfers antibiotic resistance
specialized transduction
lysogenic phage inserts itself into bacterial DNA and makes prophage
- later prophage excises itself with surrounding host DNA
- can transfer toxins this way
R factor
non-chromosomal DNA with genes for antibiotic resistance
-may move next to F- plasmid and get transmitted
how methods of bacterial gene transmittal and acquired genes contribute to pathogenicity and resistance
- resistance genes can be acquired through conjugation, transduction, transformation and mutation
- transposons move: resistance genes may move next to plasmid and get transmitted
- compound transposons resistant to multiple things
- pathogenicity islands: area with several genes that contribute to pathogenesis
commensalism becoming pathogenic
- commensalism assume compartments and immunocompetency
- immunosupressed allows runaway growth
- if commensal bacteria transferred to baby during birth
- antibiotics can throw off balance and allow overgrowth
normal flora definition and examples
commensal bacteria and yeast usually present in GI, resp, intestinal tracts and skin
GI - lactobacilli maintain low pH vagina, E coli may cause UTI, B strep in vagina bad for baby
Skin - staph epidermidis, C albicans
Resp - nose and throat have strep, staph, Neisseria. Staph aureus and N meningitidis may overgrow
- in mouth S mutans normal but good hygiene keeps it out of heart
intestinal - small intestine has strep, lactobacilli, yeast
colon - bifidobacteria, coliforms, clostridium, etc
colonization resistance
- a form of symbiosis
- prevent pathogens from successfully colonizing host
- part of innate immunity
- adaptive immunity will take over if they do colonize
communicable vs contagious infection
communicable - passed from host to host
contagious - highly communicable
non-communicable - comes form environment rather than a previous host
latent infection
disease subsides but microbes stay and restart disease later in life
- chicken pox and herpes
chronic carrier
host survives disease but continues to shed pathogens indefinitely. hepatitis.
types of parasites
- pathogens are parasites bc they cause harm
1. obligate intracellular parasite - must enter host to reproduce
2. facultative intracellular parasite - can reproduce outside of host
complement
binds to antibodies that are already bound to antigens. also binds the antigen, releases aflatoxin induces phagocytosis and MAC
virulence factor activity
- survive extreme environment - tolerates pH, drying, detergents. siderophores can get iron out of globins
- adhesion - use pili, slime layer, adhesins to stick to host surface
- immune invasion - capsules to resist phagocytosis, IgA protease, induce macrophage apoptosis, antigenic variation, serum resistance for complement in A aureus
- take over host cell
type 3&$ secretions - bridge cytoplams of bacteria and host to condition host. transport proteins and DNA
-endosome escape - grows inside macrophage and later lyses cell and spreads
-actin polymerization - force host to polymerize its own actin that it shoots out - Poison Host- exotoxins, endotoxins, tissue degrading enzymes
Endotoxin structure
- g- cell wall
- immunogenic symptoms: overproduce TNF and IL1
- produce fever and shock
- damage endothelium causes hypotension
- clots and massive bleeding in other spots
- activate complement
- SIRS : systemic inflammatory response syndrome. over produce cytokines and complement
exotoxin
g+ or g-
secreted from cell
most toxic
often on plasmids or phage
heat liable
can raise antibodies against inactive form
A and B subunits: A for toxicity, B binds host
Koch’s Postulates
for proof of causality
- observe potential pathogen in sick animal
- grow pure culture of pathogen
- infect new animal
- observe same disease
- culture same pathogen from new animal
- if fulfilled you can say it causes disease
how normal flora become anaerobic pathogens
escape normal compartment or form abscess
- actinomyces is normally in mouth but can cause abscess that needs draining
- B fragilis normally in colon but infection if gets into blood
how anaerobes in environment become pathogens
- spore formers - enter wounds, germinate, form toxins
- ex: C tetani, C fergrigens, C botulinum - through food - spores survive inadequate sterilization and live in airtight can. once exposed to air they die but toxin remains
ex: C bot and C perfrigens
technique to culture and identify anaerobes
- need to handle anaerobically, add reducing agent to rid O2, fill tube all the way, stopper tight, do not shake
- use glove box or airtight jar and gas pak and incubate anaerobically
- identify with staining, GC or DNA sequencing
anaerobic pathogens with soil reservoir
C tetani, C perfrigens, C botulinum
anaerobic pathogens that start as normal flora
C dfi, GNAB, actinomyces
exotoxin producing anaerobes
C tetani, C botulinum, C perfrigens, C dif, GNAB
anaerobes that cause abscesses
GNAB and actinomyces
treatment for anaerobic caused infection
- Abscess - drain or surgically remove
- Toxigenic - use antitoxin
probably use an antibiotic afterwards too
Spirochete common themes
- Transmission - sexual, vector-borne, environmental. cross easily into blood and even BBB
- Pathogenesis - not very antigenic; immune evasion. little inflammation, few exotoxins. can’t make vaccines against it
- Diagnosis - challenging bc wide variety of symptoms, might develop in phases over months or year, lab tests unuseful (treponema too small to see under microscope) (lyme requires interpretation rather than +/-), eye exam may help
- Treatment - antibiotics early on; they are not very resistant. later can still be curable but nervous/muscular complications may persist.
Jarisch-Herxheimer reaction - get it24 hr after antibiotics because immune system wakes up
Vibrios common themes
- Transmission - fecal oral route, infect wounds contaminated by seawater, H. pylori causes peptic ulcers
- Virulence - fecal - oral enteritis and ulcers require GI virulence factors for attachment. may use phage and endotoxin
- Diagnosis- exams and symptoms or lab test
- Treatment - antibiotics, hydration, electrolytes
syphilis
3 stages from painless chancre to rash with flu-like symptoms (meningitis possible) to latency or dangerous cardiac or CNS symptoms (gummas possible).
-congenital syphilis is devastating and preventable with prenatal care
borellia burgdoferi
- lyme disease
- tick borne, rodents and deer ticks
- requires 24 hr to transmit, remove with soap and tweezers
- 3 phaes:
1. early localized; rash
2. early disseminated; meningitis, facial palsy, rash, cardiac symptoms
3. lat disseminated; arthoritis, encephalitis
treat with doxycycline for no more than 1 month
V cholerae
complex lifestyle outside host. has O1 marker of colonization for lysogenic phage colonization.
- transmitted fecal - oral
- if stomach acid doesn’t kill it, secretes mucinase to attach to intestine
- after attachment, secrete choleragen, an AB enterotoxin that disrupts signal transduction and cause diarrhea
- don’t necessarily need antibiotics in a previously healthy person
- need to hydrate and restore electrolyte balance
obligate vs. facultative intracellular pathogens
obligate - need host to grow. for lab diagnosis need a tissue cell culture for it to grow on media
ex: chlamydia, rickettsial, viruses
facultative - can grow outside host if nutrients are available
ex: Cocci, Enterobacteria, mycobacter, Bacilli, Fungi, Legionella, Listeria
3 major pathways intracellular pathogens use to survive endocytosis and establish infection
- Escape - get out of endosome with proteases and flood cytosol before lysosome can degrade it.
- Subvert - dont allow lysosome to bind to it.
- survive - can neutralize acidic pH and degrade hydrolytic enzymes
Reoccuring themes in intracellular bacteria pathogenesis
- Ride on infected macrophages to travel through bloodstream and spread (Enterics -> TB, Mycobacter-> typhoid fever)
- Actin - actin tails help to spread (Shigella and Listeria)
- Type 3 secretions
- inactivate lysosomes or enhance phagocytosis
(Legionella, Enterics, mycobacter) - Evade humoral immunity - can get through colonization resistance. Enterics enter through M cells of peyer patches and onto sterile exterior of intestinal epithelium –> gastroenteritis)
*effective antibiotics must penetrate cell membrane, not just travel through blood
Listeria monocytogenes
- facultative intracellular pathogen
- escapes endosome
- actin motility to spread
- cause gastroenteritis, which is self limiting in healthy ppl
- in YOPIs its bad
- pregnant women - bad for fetus
- immunosuppressed- may cause meningitis
- often in deli meat and soft cheese
Chlamydia
- elementary bodies infect, turn to reticulate bodies which multiply, then back to elementary bodies to spread and infect others
- may cause reactive arthritis
- genital chlamydia may hide behind another STI
- partner needs to get treated too to prevent reinfection
- presents as conjunctivitis in newborn
membrane features
phospholipids, proteins and carbs
- fluid bilayer
- non covalent bonds
- impermeable to large, polar, charged
Membrane function
- semi permeable barrier
- compartmentalization
- identification - proteins, lipids and carbs on outside
- signaling
- energy storage - create gradient
structure and orientation of major lipids of membrane
- phospholipids most common - glycerol backbone, fatty acid tail, phophate+alc head. amphipathic. forms bilayer that folds on itself
- glycolipids - have sugar attached to sphingosine
- cholesterol - planar, hydrophobic fused ring, stiff
- sphingomyelin - sphingosine with phosphoryl choline head
Fluidity of membrane
depends on temp, length and degree of saturation of fatty acids
permeability of membrane
small uncharged non polar > small polar > large polar > ions
peripheral vs. integral proteins in membrane
peripheral - can remove w/o disrupting membrane. bound to membrane or integral protein
integral - amphpathic. hydrophobic alpha helices on inside. topography is established and they do not flip flop once established in membrane
membrane lipid synthesis
- made on cytosolic side of rough ER
- scramblase distributes new lipids evenly between the 2 layers
- packed into vesicles and transported to plasma membrane, endosomes, lysosomes, golgi, etc
- flippase moves the lipids to establish the correct asymmetry
enterobacteriacae foodborne and opportunisitic pathogens
foodborne - shigella, salmonella, yersinia, E coli
(wash hands and food to prevent fecal-oral contamination)
opportunisitc - klebsiella, enterobacter, seratia, proteus, providencia, morganella
enterobacteriacae traits
g- rod, facultative anaerobes, glucose fermentor, non-spore, catalase +, oxidase -
pili + T3SS
Horizontal genetic transfer
acquire new virulence factors and antibiotic resistance this way
antimicrobial sensitivity testing
every enterbacteriacae infection that needs treatment needs antimicrobial sensitivity testing because they are so resistant.
- need culture of patient isolate spread on agar
- place several antibiotic disks
- allow to incubate over night
- zones of inhibition are where antibiotic worked/bacteria was sensitive to it and not resistant. will grow if resistant.
Pili and t3SS for enterobacteriacae
pili for attachment
- T3SS for attachment and to inject (needle shaped)
- inject into M cells of peyer patches in intestine, makes M cell more likely to engulf it
- then can survive macrophage
- induce apoptosis and travel to exterior epithelium and cause enterocolitis
- or travel on macrophages to lymph nodes (systemic lymph node infection may turn to typhoid fever by S typhi)
HUS and reactive arthritis
Hemolytic uremic syndrome - a complication of Shigella or E coli infection. Shiga toxin released into blood and causes hemolysis, thrombocytopenia and uremia. in kids, 5-10% mortality
Reactive arthritis - if genetically predisposed and get infected by shigella, salmonella, yersinia, campylobacter, chlamydia,
-conjunctivitis, urethritis, arthritis
ICU enterobacteriacae
- klebsiella, enterobacter, morganella, serratia, proteus, providencia
- commensal, normal flora that become pathogens
- affect already immuno-compromised hospital patients and are very antibiotic resistant, making it hard to treat
- clean catheters and scrub equipment, don’t keep patients longer than necessary
cocci genuses
all cocci are spherical and non spore forming
- Staphylococci (clumps, catalase +)
- Streptococci
- Neisseria (only g- cocci)
Staphylococci aureus
virulence factors:
- Protein A - binds immunoglobulins
- Capsule - inhibit phagocytosis
- toxins - coagulase, protein A, enterotoxin, exfoliatin, leukocidin, toxic shock syndrome
abscesses are common
Transmission - normal in nose and throat of some people. spread by direct contact or fomites
Staphylococci epidermidis
normal flora of the skin
-low virulence but easily attaches to plastic and infects catheters and piercings
Staphylococci saprophyticus
minor cause of UTI
stretococci pneumoniae
capsule is an antigen and virulence factor
-found in throat of 50% of people
strep mutans
virulence:
1. enzymes that metabolize extracellular polysaccharides
2. acids that decalcify enamel and dentin
reservoir - in everyones mouths
Strep pyogenes (group A)
virulence: pili, M protein, toxins
reservoir: in pharynx and skin of 10% of people
Strep agalactiae (group B)
virulence: capsule prevents phagocytosis
reservoir: in 25% women genital tract. can be passed to baby
group D strep/ enterococcus fecalis
normal flora of colon
can cause abdominal abscess, UTI, endocarditis
peptostreptococci
- found in abscesses with a mix of organisms
- normal in various body sites
Neisseria meningitides
polysaccharide capsule
in resp tract of 5% of people
transmitted by droplets
Neisseria gonorrhoeae
pili for attachment
-sexual or neonatal transmission
