Alistair Brown Flashcards
double check recap (123 cards)
1
Q
Define ‘bacteriostatic’.
A
a substance that prevents the multiplying of bacteria without destroying them.
2
Q
Explain growth curve of bacteria under a bacteriostatic antibiotic.
A
1) introduce antibacterial during log/exponential phase of growth curve: growth curve will stay in plateau . The curve does slightly go down bc natural cell death still occurs toxins being produced.
3
Q
Which drugs are bacteriostatic?
A
chloramphenicol erythromycin clindamycin tetracyclines sulfonamides trimethoprim
4
Q
Bacteria was put under bacteriostatic antibiotic. If you transfer the bacteria back in fresh culture media, will it continue to grow?
A
yes.
5
Q
If you give bacteriostatic antibiotic at a high enough concentration, it becomes bactericidal. However this is not given. Why?
A
don’t do this bc toxic effects on the host/patient cells. antibacterials/fungals/virals also cause damage to host cells too not just microorganism cells. that’s why have to be careful and not for too long, 14 days max if possible.
6
Q
Define ‘bactericidal’.
A
a substance which kills bacteria.
7
Q
Which drugs are bactericidal?
A
beta-lactams quinolones rifampin metronidazole vancomycin aminoglycosides
8
Q
Bacteria was put under bactericidal antibiotic. If you transfer the bacteria back in fresh culture media, will it continue to grow?
A
only slight growth (bc 100% wont die).
9
Q
Explain growth curve of bacteria under a bactericidal antibiotic.
A
growth curve:
usually put antibacterial in the exponential face> instead of going up during exponential phase, will plateau off then drop down bc bacteria death.
10
Q
which drugs inhibit folic acid synthesis?
A
sulfonamides
Trimethoprim
11
Q
what is tetrahydrofolate/Tetrahydrofolic acid? Why is it so important?
A
a folic acid derivative.
important because INVOLVED IN THE FORMATION OF NITROGONOUS BASES.
purine bases, thymine and methionine.
methionine is Amino acid> first amino acid incorporated into 70s ribosomal complex. first amino acid in translation. inhibiting dna replication, transcription translation, protein synthesis.
12
Q
Explain mechanism of action of Sulfamethoxazole to clear an infection.
A
sulfamethoxazole inhibits (PABA) Para-aminobenzoic acid>inhibits dihydrofolic acid synthesis in bacteria, which in turn stops tetrahydrofolic acid synthess
is.
Wont kill organism by blocking this system.
what it actually does it stop the organism from growing via downstream processes.
folic acid> utilized in v important biological processes.>making nitrogenous bases and amino acids.
during infection, bacteria in unfavourable environment bc host immune syst repeatedly damage the bacteria, producing ROS-damaging its outer membrane, damages its DNA- adding free radicals onto it. Must make new DNA BC has to repair DNA and fix its membrane, produce new peptidoglycan, make new proteins. must be able to transcribe regularly. so must repair dna damage/make new DNA, Which requires nitrogenous bases. also need to make new mRNA to make the new proteins. sulfonamides target PABA and stop THF. hosts cells damages all the bacteria, and sulfonamides stop it from repairing the damage. TOGETHER the antibiotics and host immune syst. clears the infection.
13
Q
Explain why folic acid synthesis pathway is a good target for antibiotics?
A
production of folic acid in humans is diff than bacteria. bacteria have to synthesize, but humans get from diet.
»>targeting the synth. pathway reduces amount of toxicity to host. don’t target human biosynth. of folic acid.
14
Q
Explain mechanism of action of trimethoprim.
A
Trimethoprim inhibits dihydrofolate reductase»>inhibits formation of tetrahydrofolic acid from dihydrolic acid.»inhibits formation of nitrogenous bases and amino acids.
15
Q
How do most antibiotics covered in lectures work?
A
WORKS TOGETHER WITH HOST CELLS TO CLEAR THE INFECTION. host cells damage bacteria DNA , antibiotics prevent repair mechanisms.
16
Q
Name some DNA topoisomerase inhibitors.
A
- Fluoroquinolones (Cirpofloxacin, Moxifloxacin, Levofloxacin)
- Quinolones (nalidixic acid)
17
Q
Explain mechanism of action of fluoroquinolones.
A
Fluoroquinolones bind to 2 nuclear enzymes > topoisomerase I/IV so inhibits unwinding of DNA, this inhibits dna replic.
so inhibits new DNA from being made. again, wont kill bacteria but when in host, unfavourable condition, stop bacteria repairing itself.
18
Q
Name an antimicrobial which damages DNA.
A
Metronidazole.
19
Q
Explain the 2 ways which metronidazole damages DNA.
A
Thioredoxin reductase (TrxR) activates metronidazole to the 2 reactive oxygen spieces (ROS). (both diagrams). the free radical version on the right binds to thiols (cysteines) of proteins and causes interactions w the disulfide bridges >damages protein OF these antioxidant defence proteins and inactivates them.
double bonded oxygen version on left interacts w oxygen spieces floating around in the organism and creates ROS or reactive nitrogen intermediates (RNI).
dual effect. activated metronidazole stops the enzymes (antioxidant defence proteins) which protect against ROS, AND makes more ROS. ROS destroy dna. so cells now more vulnerable to oxidative stress..
20
Q
Name an antimicrobial which inhibits mRNA ?
A
Rifampin.
21
Q
Explain mechanism of action of rifampin.
A
RIFAMPIN (LEAD DRUG to treat TB) INHIBITS mRNA SYNTH.
inhibits mrna synth. directly. targets RpoB of RNA polymerase complex.>inhibits transcription , no mRNA, no protein, no cell wall repair , DNA repair etc. (in hosts cell, cant fix the damage caused by hosts immune syst.)
22
Q
Name antibiotics targeting protein synthesis.
A
- chloramphenicol
- clindamycin
- linezolid
- macrolides (erythromycin, clarithromycin, azithromycin)
- aminoglycosides (gentamicin, neomycin, amikacin, tobramycin, streptomycin)
- tetracyclines (tetracycline, doxycycline, minocycline)
23
Q
How does chloramphenicol work?
A
Chloramphenicol: inhibit formation of peptide bond between amino acids (at enzymatic activity site condesnsation reaction for formation of peptide bond). chloramphenicol blocks that active site on 50s subunit. would stop chain of amino acids formation, so no protein being formed. stop protein synth. no repair from host immune syst. repair of cell wall etc.
24
Q
How do macrolides work?
A
macrolides e.g. erythromycin and clindamycin. binds to 50s subunit REVERSIBLY to prevent transfer of peptidyl-trna from a-site to P site , inhibiting ability of ribosome at 50s subunit moving along the mRNA, stopping translocation. jams It on mRNA. cant move forward or back (for error checks either), so falls apart, mechanisms within the organism comes and breaks the complex apart. so no protein, no damage repair…….
25
Which antibiotics target the 50s subunit of ribosomes in bacteria?
macrolides and chloramphenicol.
26
how does doxycycline and tetracycline work?
aminoacyl-tRNA (trna carring amino acid) anticodon binds to complimentary codon on mrna.
tetracycline and doxycycline v flat so bind into A position on 30s ribosome subunit in mrna translation complex, and block the aminoacyl-trna binding to the mrna-ribosome complex. no protein , no repair etc.
27
How do aminoglycosides work?
bind to 30s subunit and cause misreads in genetic code, interrupting the sequences, and inactivate its ability to read codons correctly. error is produced and wrong trna binds,. error reading occurs and ribosome tries to go backwards and try and start again. if it cant do this, it will stop the translation process. again no protein, no repair.
some proteins can make it all the way through and make the protein but wrong amino acid is in the sequence, bacteria spent lots of the cells nutrients and amino acids , energy atp gdp, Ribosomes. Bacteria loses that energy for proteins which are not functional.
28
which drugs target 30s subunit of bacteria?
aminoglycosides and tetracyclines.
29
bacterial Cell Wall synthesis inhibitors?
- glycopeptides (vancomycin, bacitracin,teichoplanin)
- penicillins (penicillinase sensitive+resistant types+antipseudomonals. "…...cillin" e.g. amoxycillin)
- cephalosporins (I-V) (cef...../ceph...…)
- carbapenems(…...penem)
30
name peptidoglycan synthesis inhibitors?
glycopeptides - e.g. vancomycin, bacitracin, teichoplanin. .
31
name peptidoglycan cross linking inhibitors that target penicillin binding proteins?
penicillins, carbapenems, cephalosporins.
32
why is peptidoglycan a good target for antibiotics?
peptidoglycan in cell wall of wall. peptidoglycan specific to bacteria-less toxicity to host cells.
33
HOW DO CARBAPENEMS, PENICILLINS AND CEPHASOLPORINS WORK?
TARGET- penicillin binding proteins. if cant cross link, wont get cross linking of amino acid chains of peptidoglycan. peptidoglycan becomes v fluid and cell wall not repairable. stopping from MAKING the cross links.
penicillins cephalosporins carbapenems binds covalently (irreversible) into penicillin binding pocket stops organism from repairing its peptidoglycan. inactivates repair mechanism-killing organism by ability of organism to fix outer membrane . not targeting transcription/translation.
34
what are penicillin binding proteins? (PBP)
enzymes involved in creating crosslinks of amino acid chains IN PEPTIDOGLYCAN.
All β-lactam antibiotics (except for 1) bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases
35
How does vancomycin work?
targets pbp but CAPS the actual chain. ,Vancomycin recognizes and binds to the two D-ala residues on the end of the peptide chains inhibiting them from binding to pbp and creating the cross links.
Vancomycin has a unique mode of action inhibiting the second stage of cell wall synthesis of susceptible bacteria.
There is also evidence that vancomycin alters the permeability of the cell membrane and selectively inhibits ribonucleic acid synthesis.
36
Explain how bacteria can become resistant to vancomycin via change in target mechanism?
organism replaces alanine (Amino acid) with sugar lactose at the end of the side chains . vancamycin no longer caps the chain>bacteria resistance.
37
why target ergosterol in fungi?
ergosterol major component of fungal cell wall. ergosterol anchored into membr.
target eukaryote like fungal cell, target something mammalian cells don't have- humans don't have ergosterol but fungus cell wall do.
1) fungal cells require ergosterol for major structure of the cell wall, so without ergosterol, cant make cell wall, cant repair anything.
2) also ergosterol binds to outside of proteins that r anchored into membranes. - stabilizes them.
drugs target synthesis of ergosterol -by inhibiting this, it stops organism anchoring proteins into its membrane and overall integrity of fungal membrane, wont be able to replicate and repair any damage.
38
What do azoles (fluconazole, itraconazole, voriconazole) target in fungi against them??
TARGET and inhibit ERGOTEROL SYNTHESIS.
| target and inhibit production of ergosterol from lanosterol.>target and inhibit 14-alpha-demethylase.
39
What do terbinafines (.....fine) target in fungi against them?
terbinafine - inhibits lanosterol synthesis - targets and inhibit squalene epoxidase. terbafine inhibits squalene epoxidase converting squalene into lanosterol (> ergosterol. )
40
what is problem with targeting ergosterols?
we have sterol biosynthesis in our bodies>cholesterol>sex hormones synthesis. so antifungals aren't very good to keep taking.
41
why are Beta-(1,3)-d-glucans a good target against fungi?
```
caspofungin target complex sugars on outside cell wall. -unique to fungal cells, we don't have them - good,
targets B(1,3)-d-glucans.
```
42
mechanism of caspofungin?
INHIBITS CELL WALL SYNTHESIS.
Caspofungin blocks the synthesis of β(1,3)-d-glucan of the fungal cell wall, by non-competitive inhibition of the enzyme β(1,3)-d-glucan synthase. β(1,3)-d-Glucan is an essential component of the cell wall of numerous fungal species
43
mechanism of amphotericin B?
FORMS MEMBRNE PORES-CELL WALL DISRUPTION
Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death. Increase ROS entrY.
irreversible inhibitor to ergasterol . ergosterol is packed around transporter. drug breaks interaction between pore and ergosterol> reduces rigidity of that part of the membrane and loosens it up, and loosens the protein, and so pore is more open.
these transporters have transport mechanisms involved in pumping ROS out of cell . porin stops working as well bc its no longer in its tighter conformation bc drug blocking ergosterol from packing around it.
>>>creating influx of ROS into fungi>DNA damage.
44
HOW DOES FLUCYTOSINE WORK?
flucytosine enters fungal cell via enzyme specifically found in fungi. not found in mammalian cells.
1) Flucytosine is converted by cytosine deaminase in fungal cells to fluorouracil, >>which then interferes with RNA and protein synthesis.
2) Fluorouracil is metabolized to 5-fluorodeoxyuridylic acid, an inhibitor of thymidylate synthetase>>DNA synthesis is then halted.
45
Antimicrobial resistance
| 3 main resistance mechanisms?
Efflux
CHANGE IN Target
Degradation
46
Explain efflux resistance mechanism.
MAJOR mechanism. ability of organism to efflux antimicrobial compound out of cells via ABC transporters using energy of ATP so compound does n0t get to the target.
GRAM positive only one membrane- has ABC transporters on only one membrane.
but gram negative more resistance potential bc has 2 membranes- ABC on both membranes.
drug has to first get in and at a conc high enough.
how becomes resistance? changing expression of genome- more protein more abc transp. in membr.
47
Explain changing target resistance mechanism .
organism will mutate its genome to introduce diff amino acids >change mrna>diff codon> diff amino acid>if the original amino acid was specific to the mode of action of the antibiotic , removing it will reduce antibiotic's propensity or reduce activity of that antibiotic- so now the target is changed so that the antibiotic is either no longer activated / or changed so that it no longer binds to the target.
48
Explain degradation resistance mechanism..
organism acquires series of genes/proteins that it can express that will degrade the antibiotic
produces a number of enzymes- plasmid borne a lot of the times (plasmid is foreign DNA introduced into bacteria by congregation or transferred from environment or between bacteria). which can degrade the antibiotics - e.g. B lactamase. >that's why some organisms resistance to penicillin.
49
What is the name of the class of antifungals that inhibit cell wall synthesis?
Echinocandins (caspofungin and micafungin)
50
What is the name of antifungals which create membrane pores?
Polyenes (amphotericin B, nystatin )
51
Which antifungal inhibits nucleic acid synthesis ?
5-flucytosine
52
Bacterial morphology types?
COCCI (diplococci, streptococci, staphylococci, coccus etc.)
BACILLUS (rod shaped) (coccobacillus, streptobacilli, bacillus, diplobacilli etc.)
HELICAL FORM (e.g. Helicobacter pylori
53
What is bacterial morphology useful for?
important for how the organism can cause infection.
54
Nearly all bacteria have a cell wall (peptidoglycan) . Why?
gives the cell shape and protects it from osmotic lysis
55
Difference between gram positive and negative bacteria?
-Gram-positive cells have a single surrounding membrane, thick peptidoglycan and teichoic acid in their cell wall.
-Gram-negative cells have two membranes:
Inner membrane = plasma membrane.
Outer membrane which includes LPS (lipopolysaccharides).
56
Describe features of Mycobacterium.
(tb bacteria.) classed as gram positive bc haven't got true outer membrane, but truly neither gram positive or negative so cant do gram staining.
inner membrane containing mycolic acid is more impermeable than a normal bacterial membrane-'acid fast.'
57
common exam question. 2 different bacteria- whats the difference between them - (about gram staining scenario)?
cell wall architecture and why they stain differently.
e.g.
Gram staining differentiates bacteria by the chemical and physical properties of their cell walls. Gram-positive cells have a thick layer of peptidoglycan in the cell wall that retains the primary stain, crystal violet.
Gram-negative cells have a thinner peptidoglycan layer that allows the crystal violet to wash out. They are stained pink by the counterstain, commonly safranin
58
Explain Gram staining steps.
```
Fixation
Primary stain (Crystal violet)
Mordant (Iodine)
Decolourisation (Acetone)
Counterstain (Safranin)
```
59
what are kochs postulates?
4 criteria designed to establish a causative relationship between a microbe and a disease:
1) The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.
2) The microorganism must be isolated from a diseased organism and grown in pure culture.
3) The cultured microorganism should cause disease when introduced into a healthy organism.
4) The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.
60
Epidemiology of H. pylori?
50 % of world population infected (most “global” infection … for life),
but 80 % of infected people experience no symptoms. 15 % develop gastric/duodenal ulcers
1-2 % lifetime risk of stomach cancer and <1 % risk for Mucosa Associated Lymphoid Tissue (MALT) lymphoma
61
How is H. pylori contagious ?
(exact route unknown) oral-oral or fecal-oral
62
H. pylori is a carcinogen, true or false?
true.
63
Describe the physical properties of Helicobacter pylori.
> helix shape
> Fast-moving with lophotrichous flagella (multiple flagella at one point on the bacterium which act as propellers , proton pumps in membrane force flagella to spin .)
> Thrive in very acidic mammalian stomach by producing urease that raises local pH from ~2 to a biocompatible range of 6 to 7 .
> Contains Adhesins (factors that aid in adherence to gastric epithelial especially In the pyloric atrium and duodenal canal)
64
there is over 20 different Helicobacter pylori species, true or false?
true
65
How does H pylori thrive in the very acidic environment of the stomach?
Raises local pH from ~2 to a biocompatible range of 6 to 7 by producing urease, which breaks down urea (found in stomach) with water into CO2 AND NH3.
NH3 neutralises gastric acid.
(also start burping a lot due to co2 production.)
66
Which of the following about H. pylori are true? (2 right answers)
1) Microaerophilic (requires 2-10 % O2)
2) Anaerobic
3) gram stains purple
4) Requires CO2 for growth
1 - requires small amounts of oxygen to grow
| 4 - can get from breaking down urea
67
H. pylori Forms biofilms (spiral to coccal transformation).
| What is a biofilm?
e.g. sludge on ur bath, tar tar on teeth.
biofilm- level of organisms that u have vegetative and planktonic (ie growing) and latent organisms all growing as 1 and secretes sugar lipid dna and rna into this mucoidy which mess protects the bacteria .
bottom bacteria aren't doing anything- antibiotics cant penetrate them- safe.
ones at top r readily growing.
68
Why is the ability of H. pylori to form biofilms a problem?
- dormant H pylori organisms just sitting in biofilm .
- bottom bacteria aren't doing anything- antibiotics cant penetrate them- safe.
- cant get rid of those H pylori bc its not growing, the immune system won't clear the organism so wont be damaged and wont have to go through transcription translation (therefore antibiotic manipulation difficult),
- it sits there until they need to respond to an environment,
69
Explain why and how H pylorus is a highly adaptive organism which lives only on gastric mucosa?
targets pyloric atrium, causes damage in this area, sometimes damage transfers into the duodenum but most of the time its in pyloric atrium and damages pylorus sphincter as well . damage at base of stomach bc that's where organism adapted to survive in the acid. Colonize pyloric atrium and cause infection.
organism utilizes the protective mucus layer as source of energy-nitrogen for protein synth, co2.
70
Symptoms of H pylori infection?
```
After several days incubation period, patients suffer mild attack of acute gastritis
• Abdominal pain
• Nausea
• Flatulence
• Bad breath
```
71
6 Adaptations of H pylori to allow it to be a pathogen?
1) Can survive and grow in the acidic conditions of the stomach:
by urease production. urease hydrolyzes urea in stomach to co2 and nh3, increasing ph of the area from around 2 to 6-7.
2) Can move through and colonize the viscous mucus layer:
(must move to colonize) organism helix shape and lophotricious flagella causing the twisting helix motion allows to drill through the viscous mucus layer so can colonize.
3) Produce Vacuolating cytotoxin (Vac A) which induces apoptosis. (expressed by majority of strains of H. pylori, appears to increase bacterial fitness):
produces VacA (vacuolating cytotoxin)> secretes into host cell , all vacuole producing proteins come together and interacts w mitochondria, vacuoles outside of mitochondria, inside of mitochondria come out. mitochondria stop functioning correctly and die>apoptosis of the cell .
4) Produces ammonia by urease hydrolysis of urea, Ammonia is toxic to the cells.
5) Produces proteases, VacA, phospholipases, CagA that can also cause inflammation
6) produce HcpA (Helicobacter cysteine-rich proteins) trigger immune response
72
Diagnosis- how can you test if someone has H. pylori?
1) Urea breath test (UBT) - good because sensitive [sensitivity/specificity 90%], and less invasive method.
2) Serological testing - (Analyses which bacteria present in stomach-be sick and test for any H pylori in the sick.)
(82.4% sensitive and 85% specific)
3) Stool antigen test - good because sensitive (89-98% sensitivity & >90% specificity ) and less invasive method.
4) Stool immunoassay & PCR- (polymerase chain reaction
identify genes which r in the pathogenicity island which r specific to H PYLORI ONLY
PCR targets that piece of DNA, PCR fragments then H pylori present.
immunoassay- immunoblot with multiple antigen and antibodies- interact w one another bc which forms ppt of h pylori if present.)
73
Severe symptoms of H pylori infection?
Anaemia- STOMACH STARTING TO SHUT DOWN
| Weight loss - not breaking food down properly.
74
Which test is a last resort to test for H pylori, or when H pylori test results come back as negative?
Endoscopy & biopsy -
don't put on exam paper because not how u diagnose someone bc more discomfort for patient, when there is other easier tests.
75
Explain how H pylori can colonize the mucus layer of the stomach via chemotaxis (–movement in response to a chemical stimulus.).
One organism swims to burrow and penetrates into the the mucus layer, change pH of the environment its in, and because its a positive environment, other organisms sense that its more positive environment than they r in, and will move by a chemical action responding to chemical stimulant towards the area that is better for them to grow in. They do this by their spiralling motion and using flagella to spin and propel them through.
H pylori bacteria produce urease to hydrolyse urea into CO2 and ammonia.
CO2 causes burping and used as nutrients by organism.
Ammonia neutralise gastric acid , increases pH of environment which destabilises mucin and de-gels the mucin layer .
and adhere to epithelial cells by adhesin production which bind to lipids and carbohydrates on cell membrane , binding to an area where they can stop and not be washed away. protective mucus layer removed by h pylori.
76
How does H pylori cause gastric and duodenal ulceration?
Ulcer formation due to Mucosal cell death caused by the cytotoxins and ammonia.
Mucinase activity causes mucosal damage which leads to Inflammation.
Inflammation is also caused by the effector molecules and proteases from the organism
epithelial cells by damaged by protease.
stomach acid now attacking exposed cells.
this damage combined with the immunogenic response and virulence factors protein H pylori secreting into the cells> leads to progression of the infection and ulceration formation.
neutrophils immunogenic response cells- induces inflammatory response, some of these factors move into the cell and cause damage to the cell itself
bacteria secretes virulence factors > switches things on and off
organisms moving around producing all their virulence factors which r being secreted into the epithelial cells or through the epithelial cells.
neutrophils immunogenic response cells- induces inflammatory response, some of these factors move into the cell and cause damage to the cell itself
77
HOW DOES H PYLORI CAUSE DUODENAL AND GASTRIC ULCERATION FORMATION IN 4 STEPS?
1) CHEMOTAXIS MOVEMENT INTO MUCUS LAYER
2) PRODUCES UREASE TO HYDROLYSE UREA TO AMMONIA AND CO2, AMMONIA NEUTRALISES GASTRIC ACID. INCREASING THE pH DESTABALISES MUCIN AND DE-GELS THE MUCUS LAYER.
3) REPLICATION AND DESTRUCTION OF MUCUS LAYER . replication of H pylori once safe/favourable environment (and nutrients by breaking down mucus layer) is established.)
4) INFLAMMATION. Mucinase activity damages the mucosa causing inflammation
Proteases and cytotoxins produced by the bacteria causes more damage and inflammation.
Effector molecules (e.g. neutrophils) causes further inflammation.
The ammonia produced to regulate pH is toxic to epithelial cells
ULCER FORMED.
78
True or false? 37-kb cag pathogenicity island (PAI) usually absent in strains isolated from asymptomatic human carriers.
True. without these genes, H pylori will not be virulent .
79
Which genes are in the cag 37000b pathogenicity island of H pylori?
1) genes which encode for proteins that together form the type IV secretion system
2) cagA genes which encodes for CagA protein.
80
What is CagA?
encoded by cagA, a major virulence protein associated with ulcers, which undergo a phosphorylation cascade involving kinases.
81
What is the type IV secretory system (T4SS)?
like needle which goes through membrane of the bacteria and created needle on the outside, allowing to attach with the epithelial cells and force its immunogenic reagents directly into the epithelial cell. -capable of delivering CagA (protein) from bacterium into host cell.
82
Which 2 molecules in gram negative bacteria like H. pylori induce inflammatory response?
Hint- one found in the cell wall
Hint- another found on outer membrane.
Peptidoglycan (PGN) and Lipopolysaccharide (LPS). Host cells response to presence of LPS.
83
Is H pylori a Koch's postulate?
not a traditional one.
84
What does CagA do?
CagA affects cytoskeleton reorganisation, breaks tight junctions between epithelial cells and cells start coming apart and lose their order>epithelial layer has holes, allowing organism to go across the epithelial layer and get further into the dermis. and also has access to a lot more nutrients by passing the epithelial layer.
85
What do the proteins involved in infection that are secreted/expressed by H pylori do ?
They start a cascade, resulting in e.g.
interleukin and tnf alpha responses.
growth factor upregulation - starts upregulating genes> (changing gene expression >cancer formation).
cagA protein involved in cancer formation.
induces RAFT of immunogenic reactions.
86
How can a patient get cancer from H. pylori?
long term damage caused by reinfection causing multiple ulcerations again and again. e.g. by not taking antibiotics.
over the years , keep getting reinfected>chronic gastritis and keeps escalating>organisms can start forming cancer .
87
First line treatment of H pylori?
PPI (e.g. pantoprazole) + clarithromycin 500 mg + amoxicillin 1000 mg minimum of 7 days
88
Second line treatment of H pylori if patient allergic to penicillin?
PPI + bismuth subsalicylate/subcitrate 120 mg QDS + metronidazole 500 mg + tetracycline 500 mg for a minimum of 7 days
89
Why are antibiotics a double edged sword?
Humans have a Complex gut micro-environment . problem w antibiotics- they r non specific- will kill flora of your stomach
90
What is the pharmacy term for food poisoning?
'infectious diarrhea '
91
Healthcare Acquired infection epidemiology (HCAIs) statistics?
300,000 patients a year in UK, costing NHS £1b a year.
92
what is a Healthcare Acquired infection?
infections that are acquired as a result of health care within the NHS. Secondary infections, the patient did not come in with this infection.
93
What is diarrhea?
Characterized by frequent evacuation of liquid stools,
Accompanied by loss of fluid and electrolytes, especially sodium and potassium. evacuation of fluid is mainly from GI tract mainly from colon and small intestine.
94
What can you do for a patient to help them with the loss of water and electrolytes (e.g. sodium and potassium) lost in diarrhea?
Dioralyte
95
How does diarrhea occur?
Occurs when there is excessively rapid transit of intestinal contents through the small intestine, decreased absorption of fluids, increased secretion of fluids into the GI tract.
96
What can happen if diarrhea progresses to a later stage?
sometimes theres not even any stool, just mucus (from mucal lining of colon) and water, can progress to later stage inclusion of blood and cells.
Can kill if not treated properly, esp if infectious. bowel wil rupture.
97
Etiology (causes) of diarrhea?
• Inflammatory disease (inflammation of the bowel)
• Infections with fungal, bacterial, or viral agents
• Medications (antibiotics, elixirs)
• Overconsumption of sugars
• Insufficient or damaged mucosal absorptive surface
• Malnutrition (when stomach swells up bc gas inside intestines- chronic diarrhoea )
>>>>>>>>Should identify and treat the underlying problem
98
Why is infectious diarrhea hard to treat?
bc don't know if to give antibacterial, antiviral or antifungal.
if this is the case then give nothing
99
Describe diarrhoea diagnostics.
Take stool samples and look for:
• Fecal fat: qualitative and quantitative to rule out fat malabsorption
• Occult blood
• Ova and parasites
• Bacterial contamination ( ecoli 0157 or Clostridium difficile, foodborne or water contamination)
• Osmolality and electrolyte composition (amount of water and electrolytes in stool)
100
List some ways which the GI tract protects itself from attack by pathogens. MOUTH?
normal bacterial flora
lysosome
Saliva
flow of liquid
101
List some ways which the GI tract protects itself from attack by pathogens. OESOPHAGUS?
peristalsis
| flow of liquids
102
List some ways which the GI tract protects itself from attack by pathogens. STOMACH?
acid ph
103
List some ways which the GI tract protects itself from attack by pathogens. SMALL INTESTINE?
```
peristalsis
flow of gut contents
normal flora
lymphoid tissue (Peyer's patches)
shredding + replacement of epithelium
mucus
bile
secretory IgA
```
104
List some ways which the GI tract protects itself from attack by pathogens. LARGE INTESTINE?
shredding + replacement of epithelium
mucus
normal flora
peristalsis
105
Faeces from humans or animals containing pathogens or toxins produced by pathogens can be ingested into the gut by humans in which ways?
- fluids (e.g. water, milk)
- food
- fingers
106
Once pathogens from faeces are ingested, they reproduce and produce toxins. Infections of the GI tract can be grouped into those that remain localised to the gut and those that spread to other sites in the body.
1) What happens to those that remain localised to the gut?
2) What happens to those that spread to other sites in the body?
1) Pathogens multiply and produce toxins in the gut. Those that remain localised in gut lead to diarrhea cause diarrhea and are excreted in faeces.
2) Pathogens invade or toxins are absorbed by the body from the gut, leading to a systemic infection. Systemic infection symptoms include fever. Pathogens are excretes in faeces.
107
Common foods that may be contaminated by bacteria that cause food poisoning/infectious diarrhea?
why is this helpful to know?
```
cooked rice
milk
eggs
dairy products
fish
```
different food poisoning bacteria are found in different food. Can ask patient what they ate, will help with diagnosis and treatment.
108
Campylobacter are the most common causes of infectious diarrhoea. Which of the following is true?
A) Campylobacter is gram positive and bacillus shaped
B) Campylobacter is gram negative and coccobacillus
C) Campylobacter is gram negative and S-shaped rods
D) Campylobacter is gram positive and Helix rods.
C. gram negative and S-shaped rods.
109
Which one is true, A or B:
A) Salmonella is a Rod-shaped, flagellated, aerobic, Gram-negative bacterium.
B) Salmonella is a Coccus- shaped, un-flagellated, anaerobic, gram-positive bacterium.
A
110
Name the strains of salmonella bacteria that causes infectious diarrhoea.
S. typhi
S. paratyphi
S. enteritidis
S. cholerae suis
111
Explain how Salmonella enteritidis causes infectious diarrhoea.
1) ingested
2) absorbed to epithelial cells in terminal portion of small intestine.
3) penetrates cell and migrate to lamina propria layer of ileocecal region.
4) multiply in lymphoid follicles causing reticuloendothelial hyperplasia and hypertrophy.
5) polymorphonuclear leukocytes confine infection to GI tract.
6) inflammatory response also mediates release of PROSTAGLANDINS which stimulate cAMP and active fluid secretin. >diarrhea
112
describe the physical characteristics of diarrhoea-causing E. coli.
facultative anaerobe
gram negative
rod-shaped
113
E. coli causes food poisoning(infectious diarrhoea) in a similar way to cholera toxin. How does E. coli cause food poisoning?
Enterotoxins cause an increase of cAMP in intestine, which causes increased Cl- secretion, after which Na+ follows, and H2O follows by osmosis.
114
Norovirus (causes food poisoning) is highly infectious. is there a treatment for it?
no. just water and dioralyte
115
susceptibility of being infected by Norovirus greatly depends on...…………...
genes - pharmacogenomics
116
Food Poisoning/infectious diarrhoea :
The symptoms usually pass within a week. Usually treat yourself or your child at home.
How to treat it?
* Stay off school or work until the symptoms have stopped for 2 days. This is when you're most infectious. • Rest and drink fluids to prevent dehydration.
* Eat when you feel up to it, but try small, light meals at first and stick to bland foods – such as toast, crackers, bananas and rice.
* Oral rehydration solutions (ORS), which are available from pharmacies, are recommended for more vulnerable people, such as the elderly and those with another health condition.
117
Food Poisoning/infectious diarrhoea :
Antibiotic treatment is not usually required, as most cases are self-limiting. Consider antibiotic treatment IF......…….what?
* Symptoms are severe - high fever, blood in stools or more than eight stools per day.
* There is immune compromise.
* Symptoms are worsening.
* Diarrhoea has lasted for more than a week.
118
Antibiotic treatment is not usually required, as most cases are self-limiting.
But if you need to, how do you treat with antibiotics?
>the first-line choice is erythromycin 250-500 mg qds for 5-7 days. (Azithromycin or clarithromycin are alternatives if erythromycin is not tolerated.)
>Ciprofloxacin 500 mg bd for 5-7 days is an alternative to treatment with macrolides.
119
Clostridium difficile bacteria (causes food poisoning/infectious diarrhoea) spreads very easily. Describe some other features.
```
>Gram-positive
>spore-forming
>anaerobic (ferments the bowels)
>motile
>ubiquitous (found everywhere) in nature, especially prevalent in soil.
```
120
C . difficile infection can pass through health care professionals.
be extra careful.
121
How does Clostridium difficile cause food poisoning?
antibiotics and kill their microflora > c difficile can outgrow the natural flora and become the predominant organism.
natural flora utulise sialic acid attached to proteins on outside epithelial cells. bacteria produce slidases which cleave off the sugar and use the sugar as a carbon source.
sialic acid comes off and utilised as carbon source. antibiotic come and kill all the flora. sialic acid still attached, mnutreitns still available. c diff carbon source instead. quite resistant to antibiotic, while everything else dies. starts causing infection.
only real way to treat is fetal matter transfer-take healthy patient, dehydrate and turn into suppositries and put it in the patient.
122
Which is the is the predominant sialic acid found in mammalian cells?
N-Acetylneuraminic acid (Neu5Ac or NANA)
123
Explain how lesions/ pseudomembranous plaques are formed by C. difficile.
(tcdA) toxin clostridium difficile A
secretes tcdA into environment.
oxic clostridium difficile B
secretes transfers across epithelial layer and interacs w neutrophils and starts causing immunogenic response, and start getting new membranes being formed .
tcdA interacts w tight junctions between epithelial cells by breaking them down> swelling.
combined effect>get a swelling- Pseudomembraneous plaques- puss filled. C difficile growing in there bc lots of nutrients available.
why does an organism induce inflammatory response? for nutrients.
apoptotic bodies> nutrients.
