Exam 3 Flashcards
1
Q
bacteria morphology
A
coccus
bacillus (rod)
spirochete
vibrios, filamentous, coccobacilli
2
Q
what is cell wall
A
rigid structure surrounding the cell membrane
3
Q
cell wall functions
A
prevent osmotic lysis
protect cell from external stresses (host)
contributes to virulence
target for antimicrobials
4
Q
what makes a bacteria gram pos
A
no outer mem
thick peptidoglycan
looks blue when stained
5
Q
what makes a bacteria gram neg
A
outer membrane w an inner (thinner) layer of peptidoglycan
looks pink when stained
6
Q
what makes a bacteria acid-fast
A
have waxes and fatty acids on the outside of peptidoglycan
hydrophobic components difficult to stain, but once stained it retains stain
red on blue
7
Q
what is the most common acid fast bacteria
A
Mycobacteria
(TB)
8
Q
what are the main mycobacterial virulence factors
A
mycobacteria are acid-fast
mycolic acid, Wax D, cord factor, arabinogalactans, and sulfolipids
9
Q
wall less bacteria stain
A
need special stain
sensitive to stress
10
Q
features of gram pos bacteria
A
thick peptidoglycan wall (chain link fence)
resist lysis by complement, but still can be opsonized
teichoic acids and lipoteichoic acids
other proteins and carbohydrates (fibrillar layer, carbohydrate capsule)
11
Q
teichoic acid
A
gram pos
Ribitol or glycerol phosphate + side chains
Involved in virulence and Ag classification
12
Q
features of gram neg bacteria
A
outer membrane (2nd lipid bilayer)
periplasmic space between inner and outer membranes
single layer of peptidoglycan in periplasmic space
porins enable diffusion across outer mem
LPS for pathogenesis
13
Q
what are polymyxins
A
work on outer mem (gram neg), work as cationic detergents
can target LPS
14
Q
LPS features
A
endotoxin for gram neg
MOST HIGHLY CONSERVED PORTION OF LPS = LIPID A
made up of lipid A and core oligosaccarides
Lipid A has endotoxin activity, beta-hydroxy myristic acid, phosphastes, and glucosamines
core is highly conserved among different bacteria
recognized by TLR4
15
Q
what does TLR4 recognize
A
LPS
16
Q
what is beta-hydroxy myrisitc acid
A
a unique C14 fatty acid
part of lipid A in LPS
17
Q
smooth vs rough LPS
A
rough = core + lipid A
Smooth = rough + O Ag
18
Q
what is O Ag
A
repeating sugar units on smooth (not rough) LPS
Antigenic and highly variable amount species and strains
19
Q
what is LOS
A
LPS without O Ag
(it ‘lost’ the O –> LOS)
20
Q
what is the most common wall less bacteria
A
mycoplasma
21
Q
features of wall-less bacteria
A
No cell wall (no peptidoglycan)
No outer membrane
Incorporation of CHOLESTEROL from host (toughens mem)
Very labile
No definite shape
Small genome
22
Q
features of peptidoglycan
A
unique to prokaryotes
lysozyme hydrolyses (breaks down) backbone
composition: N-acetyl glucosamine - N-acetyl muramic acid
pentapeptide with L and D amino acids
23
Q
what do beta lactams target
A
inhibit transpeptidation (D-ala-D-ala) of peptidoglycan
How?
Transpeptidase enzymes that cross link can recog penicillin instead of D-ala-D-ala > inactivates transpeptidase enzymes > no cross linking
bactericidal
24
Q
name the beta lactams
A
penicillins (ampicillin and methicillin) and cephalosporins
Target peptidoglycan
25
what does vancomycin target
transpeptidation and transport (binds to D-Ala-D-Ala, note difference with beta-lactams)
TOO BIG, DOES NOT WORK ON GRAM NEG
26
what does bacitracin target
lipid carriers, transport of peptidoglycan subunits across mem
TOO BIG, DOES NOT WORK ON GRAM NEG
27
beta lactams vs vancomycin
beta lactams: target transpeptidase enzymes
vancomycin: target D-ala-D-ala
28
what is the difference between gram pos and gram neg peptidoglycan
gram pos: L-lys-(gly)5-D-ala
gram neg: DAP-D-ala
(DAP acts as lysine in gram neg)
29
peptidoglycan synthesis
transport through cytoplasmic membrane
(bacitracin-sensitive)
polymerize backbone
cross-link peptides
third amino acid - NH2 side chain (lysine [gram- positives] or DAP [gram-negatives]) peptide bond displaces terminal amino acid (D- alanine) of adjacent peptide chain, crosslinking chains and conferring rigidity
30
penicillin binding proteins (PBPs)
perform crosslinking of peptidoglycans
31
pentaglycine bridge
extends from lysine to form cross-links in peptidoglycan
32
muramyl dipeptide
part of peptidoglycan backbone
N-acetyl glucosamine and N-acetyle muramic acid w two aa’s haning down
HIGHLY INFLAMMATORY
recog by TLR2
33
what does TLR2 recognize
muramyl dipeptide (part of peptidoglycan layer)
34
bacteria capsule
aka slime layer or K Ag
not impermeable
Both gram pos and gram neg can make
made of polysaccharides
important for virulence : inhibits complement and phagocytosis
35
what is glycocalyx
extracellular polysaccharide important for biofilms
36
flagella
aka H antigen
propeller
motility and chemotaxis
recognized by TLR5
37
what does TLR5 recognize
flagella
38
Pili/fimbriae
2 diff types: adherence and genetic exchange, some do one or the other, some do both
39
fibrillar layer
fuzzy protein coat on surface
virulence
40
bacterial spores
certain gram pos only - both aerobic and anaerobic
metabolically inactive
resistant to heat (boiling), desiccation
contain dipicolinic acid
41
vegetative state in bacteria
growing
42
germination in bacteria
spore goes to vegetative (growing) state
43
sporulation in bacteria
vegetative makes spores in response to stress
44
bacterial cytoplasmic mem functs
ONLY INTACT LIPID BILAYER
transport: facilitated diffusion, active transport, group translocation (phosphotransferase – carbos)
electron transport and oxidative phosphorylation
energy production
motility
replication (no actin or MTs, used to separate chromosomes
45
what is group translocation
phosphotransferase used to move carbs, phosphorylation of carb to transport it
46
nucleoid
Single, circular structure (haploid genome) --> mutations result in dominant phenotype
Not in nucleus - no nuclear mem, Transcription in cytoplasm w translation
Supercoiling - DNA gyrase --> important for DNA replication, can store energy
47
what do quinolones target
gyrase (supercoiling) and DNA rep
48
name the quinolones
nalidixic acid
49
what does metronidazole target
incorporated into DNA after reduction by anaerobes, inhibiting DNA replication
50
fermentation v respiration
fermentation = organic e- receptor
respiration = inorganic e- receptor
51
obligate aerobes
require oxygen
52
facultative anaerobes
grew well in presence or absence of oxygen
53
microaerophilic
prefer low oxygen
54
aerotolerant
tolerate low amounts of oxygen
55
obligate anerobes
cannot tolerate oxygen
56
siderophores
high affinity for Fe, take the Fe from host to use for replication
important for virulence
57
folic acid metabolism
humans need to consume it, bacteria need to synthesize it
THFA acts as a C donor, then becomes DHFA, needs to be recycled
58
what does trimethoprim target
inhibits dihydrofolate reductase
folic acid recycling
blocksconvertion of DHFA back to THFA
technically also affects humans but much more severe for bacteria
59
what does sulfonamide target
blocks folic acid
acts as a PABA analog that inhibits dihydropteroate synthetase (not in humans, needed for folic acid metabolism)
60
bacterial RNA polymerase
Alpha-alpha-beta-beta' is core, has enzymatic activity
also need sigma to binds to promoters, but the pol is technically just the core
61
what is bacterial holoenzyme
alpha-alpha-beta-beta' core + sigma
62
what does rifampin target
RNA synthesis (beta subunit of RNA pol core)
63
Factor independent vs Rho dependent transcription
factor independent - default
rho dependent - RNA pol needs additional subunit for transcription
64
how is transcription regulated in bacteria
initiation is regulated
once transcription starts, it just goes
65
polycistronic operons
several genes transcribed from same promoter and regulated by the same conditions
66
lac operon
Absence of lactose: Lac I binds operator (o, between promoter (p) and gene), prevents Pol from transcribing > no transcription
Lactose present: inducer (allolactose/lactose/IPTG) binds Lac I, prevents Lac I from inhibiting operator, Pol functs
RNA POL CAN BIND PROMOTER IN BOTH, LAC I JUST BLOCKS IT BY BINDING O
needs 2nd signal from CAP+cAMP
67
quorum sensing
important in biofilms
small inducer molecules secreted
when conc reaches threshold (quorum has been attained) > gene expression changes
68
what is the main difference between transcription and translation in humans v bacteria
bacteria = co-transcription-translation
no mem, no nucleus, both happen at same time in cytoplasm
69
what do aminoglycosides target
ribosome (translation)
70
name to the aminoglycosides
streptomycin, kanamycin, gentamicin, neomycin
(target ribosome)
71
what does tetracyclines target
ribosome (translation)
bacteriostatic
72
what does chloramphenicol target
ribosome (translation)
73
what does macrolides target
ribosome (translation)
74
name the macrolides
erythromycin and azithromycin
(target ribosome)
75
where can protein localize to
Cytosol (Cytoplasm), Cell mem, Periplasm (gram-neg), Outer mem (gram-neg), Extracellular, Inside host cells
76
what pathways mediated secretion in bacteria
Primary = Sec pathway (uses N terminal hydrophobic leader seq) Secondary = Tat (twin arginine transport)
77
type 2 secretion
gram neg, get past outer mem
use SecA and YEG to get protein to periplasm, then beta barrel pushes it out
78
type 5 secretion
gram neg, get past outer mem
similar to 2 but uses single peptide (instead of SecA and YEG) to push out, one peptide for all excretion functions
79
type 3 secretion
gram neg, get past outer mem
uses complex of many proteins in mem, span periplasm, form pore to outer mem, form needle to inject to host cell; No sec
80
bacterial growth phases
lag
exponential
stationary
81
how to calculate number of generations from growth numbers
3 gen = 10x inc
How many gen from 10 to 1000 bacteria > 10^2 inc > 3 gen = 10x, so 2*3 = 6 generations
82
biofilms
communities on solid/liquid environments
features: glycocalyx holds cells together, slowed metabolism,
resistant to antibiotics and host defenses, quorum sensing
83
glycocalyx
holds cells of a biofilm together
84
planktonic bacteria
free individual bacteria not part of biofilm
85
mesophile
bacteria that grow best at body temp (37' C)
86
fastidious bacteria
require many nutrients provided to them
87
simple bacteria
make everything (nutrients) from scratch
88
features of bacterial genome
HAPLOID (no dom or recessive genes)
required: chromosome
optional: plasmids, bacteriophage, insertion seq, transposons
89
macro-mutation
affect >1 base (insertion, deletion, inversion, duplication)
90
effects of mutations
silent, loss of function, altered function
Completely new genes are not constructed by a single mutation, need many
91
importance of genetic exchange
antibiotic resistance, changes in virulence, changes in Ag makeup (avoid imm resp)
92
mechanisms of genetic exchange
transformation - uptake of naked DNA
transduction - bacteriophage as vectors
conjugation - plasmids moved by cell-cell contact
93
transformation
uptake of naked DNA
recipient must be competent to uptake DNA
DNA enters linear > digestion > recombine to be rescued and funct in recipient
94
natural v artifical competence
competence = ability to take up DNA
only certain bacteria are naturally transformable
electroporation is artificial
95
transduction
bacteriophage as vector
96
types of phage transduction
lytic - always lyses and kills host cell
temperate - can stably infect and coexist with host cell (lysogeny) until lytic phase is induced
97
lysogeny
exists in host - stably integrates and replicates in host
98
prophage
phage genome (lysogeny)
99
lysogen
bacterial cell that the phage is in (lysogeny)
100
lysogenic conversion
phage encodes an observable funct and induces it in infected host
101
specialized transduction
phage drags along piece of bacterial genome near integration site with it when it goes lytic and makes new phage
changes the next recipients genome when it integrates
specialized bc DNA near integration site
102
generalized transduction
phage accidentally packages random bacterial genome
when capsid injects, no phage, new genes recombine to cause change
caused by 'sloppy' capsid
generalized bc any random DNA (not specific to integration site)
103
lysogenic conversion v specialized transduction v generalized transduction
lysogenic conversion -- gene started as part of phage and was integrated
specialized transduction -- gene started as part of bacteria, transferred w phage DNA (near integration sites)
generalized transduction -- transfer of bacterial genes via phage (random DNA), with no phage DNA
104
conjugation features
plasmids moved by cell-cell contact
sex pilus > cell to cell contact via pilus > COPYING plasmid DNA and transfer of copy into recipient cell
(BOTH donor and recipient have copy of plasmid)
105
plasmid features
non chromosomal DNA, usually circular, transmissible via conjugation, important for virulence and antibiotic resistance
106
types of conjugation
conjugative - plasmid encodes all functs for conjugation and can move itself
mobilizable - needs help to move
non-transmissible - can't move by conjugation
107
conjugative plasmids
plasmid encodes all of the functions for conjugation and can move itself from the donor cell to the recipient cell
108
mobilizable plasmids
plasmid cannot move itself, but can be moved with help from a conjugative plasmid
109
non-transmissible plasmids
can't move by conjugation
110
F+ (conjugation)
donor, male, contains conjugative plasmid
DO NOT CORRELATE WITH PRESENCE OR ABSENCE OF F PLASMID
111
F– (conjugation)
recipient, female, receives the plasmid
DO NOT CORRELATE WITH PRESENCE OR ABSENCE OF F PLASMID
112
Hfr
high freq of recombination
plasmid integrates into chromosome, conjugation will move part of the chromosome into the recipient
113
F'
excised plasmid w additional donor DNA accidentally brought with it (kinda similar to specialized transduction)
important for E coli
114
phage v plasmid DNA transfer
plasmids are more promiscuous in their host range
115
R plasmid
resistance genes
multiple resistances
rapidly transferred to diverse bacteria
transposons
116
transposition
move from one site in DNA to another within the same cell
117
Insertion seq (IS)
gene encoding transposition enzyme (transposase) flanked by inverted repeats of DNA sequence
can interrupt genes if they insert into them
118
transposon (Tn)
gene encoding observable funct flanked by two copies of an insertion seq
can move genes between chromosomes and plasmids or between diff plasmids
can result in plasmids with multiple antibiotic resistance
119
phase v antigenic variation
phase variation - change in seq leads to On-Off or A-B switch of two diff genes, caused by inversion of a DNA seq
Antigenic variation - change in DNA seq leading to switch of expression among multiple possible genes
120
phase variation
change in DNA seq leads to an ON-OFF or A-B switch of two diff genes
caused by inversion of a DNA seq
121
antigenic variation
change in DNA seq leading to switch of expression among MULTIPLE genes
most common -cassette model
122
Casette model
antigenic variation
non-expressed copies (silent) of a gene (the cassettes) are copied or recombined into a site where the cassettes can be expressed
123
operon
region of DNA (genes and required cis-active sites) expressed from same promoter therefore on same mRNA
(Bacteria can have polycistronic operons)
124
cistron
a single gene
125
regulon
regulated by same regulator
126
stimulon
regulated by same stimulus
127
catabolite repression thourgh CAP
global regulatory mech
CAP = activator
cAMP present in low ATP
cAMP binds CRP/CAP to activate it
CRP-cAMP binds DNA, can recruit RNA Pol
CRP regulon genes usually have weak promoters (low RNA pol binding), need 2 levels of regulation to activate
128
lacUV5
mut lac operon promoter
not sensitive to catabolite repression
129
trp-lac fusions
mut lac operon promoter
tac promoter stronger
trc even stronger
make it easier to express lac operon
130
Arabinose operon overview
pBAD promoter expresses araB, araA, araD
araC encodes activator AraC
CRP binding site: identical to lac operon
2 operators (pBAD and pC)
araI additional AraC binding site
AraC can be P1 (anti-activator) w/o arabinose or P2 (activator with arabinose)
131
arabinose operon - no arabinose
AraC in P1 form binds araO2 and araI > forms bend in DNA > prevents transcription
AraC P1 represses its own synthesis at araO2
132
arabinose operon - with arabinose
AraC in P2 form binds to araI > activating pBAD > activation
CRP + cAMP must ALSO bind to relieve catabolite repression
133
trp operon
TrpR repressor only binds to the operator and represses ptrp in the presence of Trp (corepressor) --> prevents syn of trp in presence of trp
has attenuation mediated by B:C (no trp) or C:D (trp) pairing
activation in 2 parts: trp binding trpR repressor and trp causing C:D pairing
134
trp operon - no trp
ribosome stalls b/c no trp in environment,
enables B:C pairing, no C:D
135
trp operon - with trp
ribosome moves through all the way to stop codon
prevents B:C pairing
enables C:D --> acts as factor- independent terminator
136
two component regulatory systems
affect transcription
Usually 2 proteins
Sensor (S, His kinase) and Receiver (R, transcriptional regulator, regulated by phosphorylation)
Both domains can be on same protein
often span cell mem
phosphorylation of S > transfer to R > R eff funct
137
selective toxicity
toxic to bacteria but not humans, based on diff in physiology
138
therapeutic index
toxic to human / therapeutic against bacteria
want large toxic dose and small therapeutic dose --> high index
139
allergenicity vs toxicity
allergen dependent on indviduals imm sys
toxicity affects all of us
140
MBC
minimum bactericidal conc
lowest dose for complete killing
want low dose
measured by serial dilution and plating
only for bactericidal antibiotics
141
MIC
minimum inhibitory conc
lowest dose for statsis
measured by serial dilution and turbidity
want low dose
142
bactericidal vs bacteriostatic
cidal --> kill (irreversible)
static --> stop growth (reversible)
static drugs will allow growth again after they are removed
143
organ important for excretion of antibiotic
kidneys
144
organ important for metabolism of antibiotic
liver
145
broad vs narrow spectrum antibiotic
broad good for unknown bacterial agent with serious effects
narrow (specific) good for known bacterial agent
146
where are the majority of antibiotics used
agriculture as growth supplement
147
mechanisms of antibiotic resistance
enzymatically modify or degrade the antibiotic
alter the target of the antibiotic
pump out antibiotic
dec uptake
innate resistance
148
bla gene
beta lactamase
can be counteracted w clavulanic acid
149
cat gene
chloramphenicol acetyl transferase
150
aph gene
aminoglycoside phosphotransferase
151
what is the most common way to alter the target of an antibiotic to develop resistance
spontaneous mutations (retain original funct)
152
example of enzymatic modification
methylation of rRNA, gives erythromycin resistance
153
example of new biosynthetic pathway yielding altered target
vancomycin resistance,
cannot inhibit D-ala-D-lac (usually targets D-ala-D-ala) – not a point mut, too big a change
154
example of acquiring new enzymes that are resistant
MRSA, permanent change in genome in the penicillin binding proteins (PBPs), likely from diff organism via horizontal gene transfer before antibiotics were being used
155
example of pump out antibiotic
tetracycline resistance (tetA)
multiple antibiotic resistance (MAR, broad spectrum, pumps out many things)
156
example of decreased uptake
smaller specific porins - multiple antibiotic resistance (MAR)
157
example of innate resistance
Gram neg cannot take up large molecules
Wall-less don’t have peptidoglycan to target
158
plasmid vs chromosomal resistance
plasmid: new enzyme to modify/pump,
new enzyme to modify target, new biosynthetic pathway/target
point mut: target changed, not recognized by antibiotic, retains cellular function
159
common spontaneous point mutations
gyrA - DNA gyrase, resistant to nalidixic acid
rpsL - ribosomal protein, resistant to streptomycin
rpoB - RNA pol, reistant to rifampin
160
why use multiple antibiotics for TB
high mut rate allows for antibiotic resistance
161
infectious disease definition
cycle of biological interactions between pathogen and host
requires damage
162
colonization definition
Presence of microorganisms without disease at that point, applies to surfaces only (skin, mucosal epithelium, but not blood)
163
2 definitions of infection
in patients: disease (opposite of colonization)
in site of body: presence of microbes (disease or not)
164
carrier state
colonization w pathogen
165
overt pathogen
strict, primary
high probability of causing disease in an otherwise healthy host
166
opportunistic pathogens
low probability and usually require a debilitated or compromised host (not necessarily immunocompromised)
167
normal flora definition
frequently found on or within the body of healthy persons
can cause disease under right conditions
presence of bacteria doesn't mean disease
168
features of microbiota
microorganisms in or on body
not always healthy
can change
can affect many things:
metabolism/weight, immunity, resistance/susceptibility
169
microbiota v microbiome
Microbiota are the organisms
Microbiome is the genomes of the microbiota
170
common colonized sites
alimentary/intestinal tract
upper (not lower!) respiratory tract
distal genitourinary tract
skin
171
common sterile sites
blood
CSF
interstitial fluid and spaces
lymph (not active infection/draining)
172
how can normal flora cause disease
disruption of barriers
ex: endocarditis with oral streptococci
peritonitis after bowel trauma
173
protective effects of normal flora
priming immune system
adaptive - Ab against nonpathogens that cross-react with pathogens
innate - integrity of gut and production of cytokines
exclusion of pathogens from colonized surfaces
release of SCFAs and bile acids
release of antimicrobial peptides
174
non immune features of gut microbiota
degradation of dietary and mucosal polysaccharides (metabolism)
release of SCFAs
immune modulatory, metabolism
production of vitamins B and K
modification of bile acids
175
7 stages of pathogenesis
1. encounter
2. entry
3. spread (+/-)
4. multiplication
5. evasion of host defenses
6. damage
7. outcome:
(7a) transmission to new host (+/-)
(7b) recovery and treatment (+/-)
176
exogenous v endogenous infections
Exogenous – disease started soon after encounter
Endogenous – stable relationship with normal flora broke down
some microbes can be endogenous or exogenous (person A has endogenous but spreads to person B, exogenous in person B)
177
most common areas of entry
1. mucosal mem (ingestion, inhalation, sex)
2. skin surface
3. direct inoculation (trauma, bite, injection, surgery)
178
key features of adherence
mucosal surface moving fluid, must stick
specific ligand-receptor interactions - not generic
virulence factors
structures: pili/fimbriae, fibrillae
surface proteins
extracellular matrix polysaccharide and lipoteichoic acid of oral streptococci
179
key features of spread
movement from surface through tissues / body
not all bacteria spread to cause disease
bacteria CANNOT penetrate intact skin
mucosal surface is usually first barrier
cellular v tissue invasion
180
types of cellular invasion
enter professional phagocytes (MOs and neutrophils) by phagocytosis
enter non-phagocytes by bacterial mediated endocytosis resulting in phagosome/endosome (can involve type 3 secreted proteins - injected into host cell affecting actin polymerization)
other: escape phagosome to cytoplasm
181
what is the role of type 3 secreted proteins in bacterial spread
non phagocytic cellular invasion
type 3 has needle structure, can allow injection of proteins that affect actin polymerization, can cause apoptosis
182
key features of tissue invasion
between cells by:
-- degrade extracellular matrix
-- disrupt tight junctions
can use host cells to move through blood or lymph (intracellular pathogens)
183
key features of multiplication
often needed for disease
environmental variance
inoculum size
incubation period (time between inoculation and disease)
ability to aquire Fe
184
environmental variance of multiplication
tissue: intestinal lumen, blood, urine
intracellular bacteria:
cytoplasm (nutrient rich) vs. phagolysosome (nutrient poor)
presence of Fe
185
how does Fe affect bacteria
acquisition of Fe from host transferrin, lactoferrin, or other Fe-binding proteins
bacteria use siderophores as virulence factors
186
how does polysaccharide capsules evade complement
do not bind and/or activate complement
187
how does M protein of streptococci evade complement
inhibition of activation and amplification cascade
M protein in fibrillar layer binds human H factor > downregulates complement
188
how does smooth LPS evade complement
keep activation away from mem
189
how does protease evade complement
degrade the complement
190
what does C3b do in complement
opsonization
191
what does C5-9 do in complement
lysis of gram neg (not pos)
membrane attack complex (MAC)
192
what does C3a do in complement
inflammation
193
what does C5a do in complement
inflammation
194
extracellular antiphagocytic functs
inhibit recruitment via inhibition of complement and cytokines
kill the phagocytes via toxins
prevent phagocytosis by preventing opsonization, prevent binding (carbohydrate capsules)
195
intracellular antiphagocytic functs
inhibit phagosome-lysosome fusion
escape phago(lyso)some into cytoplasm
inhibit oxidative burst
resist antimicrobial functions
196
oxidative burst
rapid release of ROS, superoxide and hydrogen peroxide (H2O2)
NADPH oxidase makes superoxide, inhibiting it makes host susceptible to infections
197
intracellular antimicrobial functs
oxidative burst
acid/pH
lysozyme
defensins (cationic proteins)
198
what does lysozyme do
break down peptidoglycan backbone
199
Ag mimicry vs Ag cloaking
Mimicry – surface looks like host
Cloaking – bind host and cover themselves with it
200
Ag variation vs Ag variety
variation - change in real time, casette model (flu is exception where it is not real time)
variety - numerous already existing stable strains
201
ways to avoid Ab detection
Ag mimicry, Ag cloaking, Ag variation, Ag variety, degradation of Abs
202
modifications of cell mediated immunity
alter host response from cell-mediated (Th1) to antibody (Th2) response
203
necrosis v apoptosis
necrosis - death by lysis; via toxins (outside) or intracellular growth (inside)
apoptosis - programmed death; type 3 secreted proteins
204
what is the main way in which bacteria damage the host
non specific immunopathology: inflammation, abscess, cytokines
205
types of bacterial damage
cytotoxicity via necrosis or apoptosis --> cell death
altered pharmacology/physiology --> damage w/o cell death, can still lead to disease (and even death) on host level
206
example of specific immunopathology
cell mediated or Abs made in response to bacteria that damage the host
207
Reiter's syndrome
Heat shock protein from bacteria > imm resp > causes response to host HSPs
208
cytokines that damage host from endotoxins
TNFalpha (vascular epithelium, vasodilation, permeability)
IL1 (fever)
IL6 (acute phase, liver)
209
endo v exotoxins
endo = LPS (gram neg only)
exo = A-B proteins
210
A-B proteins
A=active portion, B=binding portion
211
exotoxin mechanisms
lysis (ex: pores), cytotoxicity (ex: altered protein syn), pharmacological (ex: cAMP levels)
extracellular enzymes (ex: protease, lipase, hyaluronidase)
superAgs
type 3 secreted proteins (apoptosis, actin polymerization)
212
super Ags
stimulate host T cell resp in Ag-independent manner
binding to Vbeta of T cell receptor resulting in cytokine cascade - similar to endotoxin
213
key features of bacterial transmission
transmission 'completes cycle'
not required for disease/pathogenesis
214
generic enteric bacteria - encounter
HUMAN FECAL contamination of food and water (direct, water, soil)
"NATURALLY" INFECTED ANIMAL FOODS - meats, dairy products, seafood (usually from processing not the animal itself)
ENVIRONMENTAL - Contamination of food with soil (usually fruits and vegetables)
215
generic enteric bacteria - entry
oral
216
generic enteric bacteria - spread
3 options: 1. no spread past intestinal epithelium, 2. invade lateral w/i intestines, 3. invade deeper to draining lymph, blood, etc
217
generic enteric bacteria - multiplicaiton
lots of food, but little or no oxygen in LARGE INTESTINE
chemical barriers to growth and multiplication - acid, bile
competition from normal flora
intracellular pathogens have difficult hurdles
218
generic enteric bacteria - evade imm defense
STOMACH - acidity; stomach is practically sterile
SMALL INTESTINE- low inoculum from stomach; digestion (especially bile), peristalsis (movement of intestine) prevents colonization
LARGE INTESTINE - normal flora made up of obligate anaerobes and some facultative anaerobes
IMM DENSES - phagocytes during inflammation; antibacterial peptides (cryptdins and defensins in crypt cells)
ADAPTIVE IMM - only sIgA (important for newborns)
219
generic enteric bacteria - damage
toxins
invasion of epithelium
inflammation
attaching-effacing adherence
vomiting
diarrhea
dysentry
220
vomiting features
rapid onset
usually toxin
221
diarrhea features
large volume, usually w/o blood or pus
usually small intestinal effects (secretory bowel)
usually from toxin
bloody diarrhea does not equal dysentery
222
dysentery features
hallmark = WBCs in stool
smaller volume, pus (WBCs), +/- blood, fever, abdominal pain
usually from large intestine (inflammatory bowel)
usually invasive organisms
223
diseases associated w dysbiosis
inflammatory bowel disease, irritable bowel syndrome, Crohn's disease
224
hygiene theory
cleaner upbringing results in less microbiota interactions, inc incidence of allergies
225
treatments to manipulate the microbiota
fecal transplant
probiotics (microbes in food)
prebiotics (compounds supporting microbes)
antibiotics
diet
226
food intoxication
no infection needed
toxin is preformed in food from contamination
227
Staphylococcus aureus features
gram pos, coccus
rapid onset, profuse vomiting, possible diarrhea
food intoxication caused by preformed toxin
228
Staphylococcus aureus - encounter
infected food handler (human reservior) that shed toxin into food
229
Staphylococcus aureus - damage
enterotoxins released into food act as heat stable SUPERANTIGENS
230
Clostridium botulinum features
gram pos rod
obligate anerobe
spore formation
preformed spore causes botulism
can also cause infant and wound botulism (rare)
231
Clostridium botulinum - encounter
spores from soil-contamination (i.e., vegetables) germinate in anaerobic but incompletely processed CANNED (autoclaved) food
232
Clostridium botulinum - damage
botulinum toxin (neurotoxin) that inhibits Ach
symptoms follow pattern: ocular > pharyngeal > respiratory paralysis > death
233
Botulinum toxin features
neurotoxin - causes flaccid paralysis by inhibiting release of acetylcholine (Ach is excitatory
A-B type; heat labile
encoded on LYSOGENIC BACTERIOPHAGE
234
Clostridium botulinum - treatment
supportive therapy (respiratory), anti-toxin
235
toxinogenic infections
not caused by preformed toxins but actual infections
236
Vibrio cholerae features
gram neg comma shaped bacterium
classified by O Ag of LPS (O:1 is epidemic)
asymptomatic, mild , or severe
severe causes rice water stool, death by dehydration
237
Vibrio cholerae - encounter
contaminated water, vegetables
environmental or human
not endemic to US
238
Vibrio cholerae - entry
pili as adherence factors
239
Vibrio cholerae - spread
none within body
localized to epithelial surface
(fecal - oral between hosts)
240
Vibrio cholerae - damage
chloera toxin
causes constitutively active adenylate cyclase > inc cAMP > diarrhea from secretion of water and salts
no cellular damage, cells can still absorb (give fluids to treat)
241
Chloera toxin features
A-B type toxin (1A and 5B)
B portion binds to GM1 gangliosides of host cells
A portion has ADP-ribosylates stimulatory G protein of adenylate cyclase --> constitutively active --> inc cAMP
causes secretion of water and salts into lumen of intestine
absorptive functions intact; no cellular damage
LYSOGENIC CONVERSION
242
Vibrio cholerae - evade imm defense
no immunological denfenses in naive host
vaccine exists but not good --> killed V. chloera injected IM, makes IgG resp not IgA resp
243
Vibrio cholerae - treatment
oral or i.v. fluid and electrolyte replacement and antibiotics
vaccine exists but not good --> killed V. chloera injected IM, makes IgG resp not IgA resp, working on live attenuated oral vacc
244
EHEC features
gram neg
can cause bloody diarrhea and hemolytic-uremic syndrome
EHEC = O157:H7 serotype
O = O Ag of LPS
H = H Ag (flagella)
245
EHEC - encounter
contaminated food from animals, mainly beef, also apple cider (and swimming pools)
bovine fecal contamination
endemic to US
246
EHEC - entry
resistant to stomach acid (low infectious dose needed to cause disease)
adherence through specialized mechanism
attaching-effacing lesion --> formation of pedestal by polymerization of actin
247
EHEC - damage
although bloody diarrhea appears like invasive dysentery (e.g., Shigella), the bacteria do not invade the epithelium, therefore little fever or pus in stool
secrete a Shiga-like toxin (SLT/Stx)
causes severe tissue damage in the large intestine, distal ileum because of capillary thrombosis (clots)
diarrhea caused by type 3 secreted proteins that stimulate ATP secretion and inc adenosine in lumen > fluid secretion
248
Hemolytic uremic syndrome
caused by EHEC
mainly in very young
SLT in blood
damage to endothelial cells of the vasculature or kidneys
renal endothelial damage
microangiopathic hemolytic anemia
thrombocytopenia
thrombosis of glomerular capillaries
249
EHEC - treatment
Symptomatic and supportive
Avoid antibiotics because they can stimulate SLT/Stx from phage and cause HUS
250
Clostridium difficile features
gram pos, obligate anaerobe, spore former
causes Antimicrobial Associated Diarrhea aka Pseudomembranous Colitis
associated w antibiotic treatment and hospital stays
251
Clostridium difficile - encounter
dysbiosis of normal flora from antibiotics
nosocomial infections
252
Clostridium difficile - damage
toxins A and B (*NOT* A-B txn)
Toxin A - inc mem permeability and inflamm in intestinal mucosa
Toxin B - cytotoxin, necrosis and epithelial destruction
mild/watery to bloody diarrhea to inflammation and ulceration
recent emergence of highly virulent strains
253
Clostridium difficile toxins A and B
toxins A and B (*NOT* A-B txn)
Toxin A - inc mem permeability and inflamm in intestinal mucosa
Toxin B - cytotoxin, necrosis and epithelial destruction
254
Clostridium difficile - treatment
antibiotics
fecal transplant (recurrent infections)
255
Shigella dysenteriae and flexnerii features
gram neg rods, enteric
diarrhea, progresses to dysentery (blood and pus), abdominal pain, tenesmus (cannot defecate), fever
256
Shigella dysenteriae and flexnerii - encounter
humans only dysenteriae NOT endemic to US
flexneri is endemic
257
Shigella dysenteriae and flexnerii - entry
highly acid resistnatsmall unoculum
infection in colon
258
Shigella dysenteriae and flexnerii - spread
laterally in intestines
(fecal-oral from host to host)
259
Shigella dysenteriae and flexnerii - damage
PLASMID-encoded cellular invasion of epithelial cells of the colon (type 3 secretion)
lyse vacuole and replicate in cytoplasm
– use host actin polymerization to move directly
from cell to cell by puncturing host
cause cell death (cytotoxicity) and ulceration, inflammation
260
Shiga toxin
Stx
ONLY dysenteriae
A-B toxin
A = inactivates ribosomes (deglycosylates rRNA) halting protein syn and killing the host cell
associated with hemolytic uremic syndrome
similar to EHEC
do NOT treat with antibiotics
dysenteriae is NOT endemic to US
261
Shigella dysenteriae and flexnerii - evade imm defense
intracellular location --> sequestered from phagocytes
if MO around, can cause apoptosis
no vaccine
262
salmonella enterica typhi and paratyphi features
gram neg
thousands of serotypes
typhoid (enteric) fever is most severe
gastroenteritis is most common
septicemia, focal infections
carrier state
few intestinal symptoms, mainly systemic (fever, shock, headache, myalgia, lethargy, splenomegaly, hepatomegaly)
263
salmonella enterica typhi and paratyphi - encounter
only in humans
indirect spread (water, food)
S. Typhi not endemic to US, S. Paratyphi is
264
salmonella enterica typhi and paratyphi - spread
invades GALT of small intestine
transcytosis through epithelial cells
infects lymph nodes, blood, spleen, liver, bone marrow, other focal organs (e.g., gall bladder)
265
salmonella enterica typhi and paratyphi - evade imm defense
resistant to phagocytes (intracellular)
resistant to complement
cell-mediated immunity more important
S. typhi (not paratyphi) have Vi capsular Ag (odd for intracellular bacteria)
killed IM vacc not good (bc induce IgG)
working on live attenuated oral vacc
266
salmonella enterica typhi and paratyphi - damage
endotoxin (LPS) and inflammation
267
non-typhoid salmonellosis features
predominantly S. typhimurium and S. enteritidis
nausea progressing to diarrhea and severe abdominal pain, can be dysentery in severe cases, infrequent bacteremia in healthy, but recurrent bacteremia in immunocompromised (AIDS)
can become systemic
268
non-typhoid salmonellosis - encounter
not human specific (human to human possible)
found in animals (poultry and bovine)
269
non-typhoid salmonellosis - spread
invade the epithelial cells of the small intestine using adherence factors and invasion factors to stimulate endocytosis by host (type 3 secretion)
transcytosis through epithelial cells
infection usually limited to intestines
270
non-typhoid salmonellosis - multiplicaiton
virulence plasmid inc growht rate in MO
271
non-typhoid salmonellosis - evade imm defense
resistant to phagocytes (intracellular)
resistant to complement (LPS)
272
non-typhoid salmonellosis - damage
inflammatory diarrhea (not toxin)
type 3 secretion
inflamm and endotoxin for systemic infections
273
non-typhoid salmonellosis metastatic infection
fever, shock, endotoxin
localized metastatic disease
gastroenteritis symptoms
274
non-typhoid salmonellosis asymptomatic carrier state
asymptomatic
can last as long as 20 weeks
275
effects of STIs
**infertility**
chronic pelvic pain
cervical cancer
liver disease
perinatal morbidity
childhood blindness
ectopic pregnancy
276
STI prevalence
1. chlamydia
2. gonorrhea
3. syphilis
chlamydia is most common
syphilis is most severe w long lasting side effects
277
core individuals (STIs)
one person who spread to many people (promiscuous individuals)
278
STI featues
encounter - human only, labile to environment
theoretically eradicable
entry - mucous mem mostly, some blood
intracellular
no vacc
279
Neisseria gonorrhea culture
normal media
280
chlamydia trachomatis culture
tissue only, obligate intracellular
281
treponema pallidum culture
not culturable
282
chlamydia trachomatis features
gram neg, obligate intracellar
many serovars
one of most common bacterial infections in US
urethritis, cervicitis, endometritis, salpingitis, epididymitis, prostatisis
pelvic inflammatory disease (infertility, ectopic pregnancy, chronic pelvic pain)
lymphogranuloma venereum (certain serovars – not endemic to US)
283
Chlamydia trachomatis - encounter
human only
sex, birth
284
Chlamydia trachomatis - entry
genital, anal, columnar epithelium
285
Chlamydia trachomatis - spread
invasion of epithelium
exit via endolysosomal pathway
MTs > peri-golgi > MT organizing center
286
Chlamydia trachomatis - multiplication
obligate intraceullar
elementary (entry) > inclusion > reticulate > elementary > exit
elementary = infective, non replicative
reticulate = non infective, replicative, alter endosomal mem fro transport
287
Chlamydia trachomatis - damage
inflammation
often asymptomatic (females don't always notice infection bc internal)
288
Chlamydia trachomatis - diagnosis
PCR
can't culture
289
Chlamydia trachomatis - treatment
antibiotics
290
neisseria gonorrhoeae features
gram neg diplococcus
urethritis, cervicitis, endometritis, salpingitis, epididymitis, prostatitis, proctitis, pharyngitis
pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain
Disseminated Gonococcal Infection (DGI)
– dermatitis, arthritis, tenosynovitis
291
Disseminated Gonococcal Infection (DGI)
spread to other parts of body
can cause dermatitis, arthritis, tenosynovitis
292
neisseria gonorrhoeae - encounter
human only
sex, birth
293
neisseria gonorrhoeae - entry
genital tract, oral, anal, ocular
columnar epithelium
pilus
Opacity proteins (Opa)
294
neisseria gonorrhoeae - spread
does not have to
some strains invade – Disseminated Gonococcal Infection (DGI)
invasion of epithelial cells via transcytosis
295
neisseria gonorrhoeae - multiplication
fastidious
chocolate agar, thayer-martin (selective)
needs elevated CO2
296
neisseria gonorrhoeae - evade imm defense
antigenic variation: pilus via cassette model and opacity proteins (Opa) via slip-stranded (post-transcriptional)
IgAse
serum resistance (DGI) via LPS + sialic acid
297
how does pili affect gonorrhoeae
Ag variation
casette model
298
how does Opa affect gnorrhoeae
Ag variation
slip-stranded mutagenesis --> 5’ has CTCTT repeat, slipping can add or delete repeats > frameshift
Post translational
299
neisseria gonorrhoeae - damage
inflamm
purulent exudate (pus)
often asymptomatic (esp female)
300
neisseria gonorrhoeae - diagnosis
PCR or culture
PCR is more common, culture used to test antibiotic sensitivity
301
neisseria gonorrhoeae - treatment
antibiotics
302
treponema pallidum features
gram neg spirochete
cause syphilis
very labile
need darkfield microscopy / fluorescence
has 1' (local), 2' (disseminated), and 3' (latent) stages
if congenital --> lethal or defects
303
syphilis stages
1' = local chancre, 3 wks
2' = 1/2, disseminated mucocutaneous skin lesions, 3 mo
can go latent, yrs, 2/3
3' = ½ of latent; bone, blood vessels, brain, gummas (granulomas)
304
treponema pallidum - encounter
human
sex, congenital, birth
305
treponema pallidum - entry
GI mucous mem
epidermal abrasions
inf endothelim
306
treponema pallidum - spread
motility via periplasmic flagella
flagella are internal
307
treponema pallidum - damage
vasculitis
3' causes imm rxns
308
treponema pallidum - diagnosis
serology – screen (anti-cardiolipin) then specific (treponemal)(cannot culture)
309
treponema pallidum - treatment
antibiotics
do not help 3' stage infection
310
stages of sepsis
SIRS (Systemic Inflammatory
Response Syndrome) > Sepsis (SIRS + infection) > Severe Sepsis (sepsis + organ dysfunct or low BP) > Septic Shock (sepsis + hypotension despite resuscitation)
311
multiorgan system dysfunct
organ failure
Overlaps w septic shock
Clotting disorders or failure of renal, hepatic, cardiac, or cognitive funct
Accumulation metabolism byproducts that cannot be cleared (e.g., lactic acidosis)
312
why inc in sepsis
people living more (aging, immunocompromised, etc)
more invasive procedures and surgeries
antibiotic resistance
inc diagnosis
results in more gram pos (normal flora) and more fungi than before
313
causes of sepsis
Bacteria (and fungi) in blood
Not all bacteremia leads to sepsis
Certain virulence factors
Invasion through skin, mucosa
inc risk in those with Granulocytopenia, PMN dysfunction, Complement defects, Adaptive immunity defects (Ig and cell mediated), Splenic dysfunction
314
sites of infection in severe sepsis
1. lungs (from pneumonia)
2. abdomen (from gut leaks)
3. urinary tract
4. soft tissues
5. IV catheters
315
host mediators of sepsis
inflamm cytokines
TNFalpha, IL1, IL6, IL8
causes fever, dec BP, inc capillary permeability flow, infiltration of neutrophils and
platelets, activation of the coagulation cascade
normal responses, just happening too much
316
sepsis symptoms
abnormal temp, low BP, mental change, renal dysfunct, techypnea (respiratory), edema, dec capillary refill, vascular occlusion
317
SIRS definition
Systemic Inflammatory Response Syndrome
Not necessarily due to infection
318
Sepsis definiton
SIRS + proven or suspected infection
319
Severe sepsis definition
sepsis + organ dysfunct (other than at site of infection), or hypoperfusion, or hypotension
320
Septic shock definition
Sepsis with hypotension that persists despite adequate fluid resuscitation and therefore requires pharmacologic blood pressure
support (“pressors” like norepinephrine)
often w lactic acidosis
321
PAMPs in sepsis
LPS, peptidoglycan, and flagella
recog by TLRs and NOD proteins
322
NFkappaB
master regulator of inflammation
PAMPs trigger NFkappaB expression, cause cytokines, chemokines, adhesion, etc
323
sepsis - damage
*acting on vascular endothelim mostly*
hypotension and capillary leak, dec perfusion, dec oxygen, accumulation of metabolites (lactic acidosis), organ dysfunct
neutrophil survival inc
Disseminated intravascular coagulation (DIC)
324
sepsis - treatment
within 1 hour
fluid resuscitation
dopamine/norepinephrine for low BP
broad antibiotics
culture blood, urine, etc
remove foreign objects (catheters)
325
ETEC disease
gram neg
Travelers diarrhea/watery diarrhea
326
ETEC - encounter
fecal-oral
human
327
ETEC - entry
oral, small intestines
328
ETEC - evade imm defense
pili/fimbriae adherence factors
there are no innate defenses in the non-immune intestinal tract that ETEC must contend with
329
ETEC - spread
no spread
330
ETEC - multiplication
there are no special/unusual growth requirements during infection or in the lab
331
ETEC - damage
Heat stable toxin, ST and heat labile toxin LT, fluid secretion
plasmid encoded
332
ETEC - mechanism of action of the primary virulence factors
fluid secretion by increased cAMP/cGMP
plasmid encoded
333
ETEC - outcome
recovery, usually even without treatment
334
ETEC - treatment
fluid replacement
no current vacc, if making vaccine use live attenuated vaccine making pili and inactive toxins
