MICROBIOLOGY Flashcards
(139 cards)
1
Q
Advantages of exotoxins
A
- May help transmission of disease – severe disease host may be an evolutionary dead end
- However, with many toxins the disease causing activity may not be primary function
- Allow colonisation, niche establishment and carriage – give evolutionary advantage
- Evade immune response, phagosomes, enable attachment to host cells
2
Q
What does Phenol soluble modulins do?
A
- PSM and alpha toxins inhibit phagosome fusing with lysosome - bacteria escape into cytoplasm.
- PSM target cohabiting bacterial species - competition.
- PSM have surfactant proteins - allow sliding movement - ADV to colonise surfaces
- Development of biofilm - alpha toxins establish cell to cell contacts - form secondary biofilm structures
3
Q
Type I exotoxins
A
Membrane acting toxin Act without cell - inappropiate activation of host cell receptors interfering with signalling. Target Guanyl cyclase = high cGMP Target adenyl cyclase = high cAMP Target Ras proteins
4
Q
Describe the mechanism for E. coli heat stable toxin
A
- Bind to GC-C receptor interfering with intracellular signalling.
- cGMP interacts with cystic fibrosis transmembrane receptor - protein kinases controlling function of specific transporters
- Affect equilibrium of ions = Cl-/HCO3- transporter and H+/Na+ co transporter affected
- high conc. Na+ and Cl- = diarrhoea
5
Q
Type 3 exotoxins
A
AB toxins
B = receptor binding and translocation
A = toxingenic
6
Q
Types of enzymatic component A - in AB toxins
A
ADP - ribosyl transferases
Glucosyltransferases
Proteases
Adenylcyclases
7
Q
Function ADP - ribosyl transferase
A
Modify activity of endogenous enzymes - covalent modification - + ribosyl groups
8
Q
Function of glucosyltransferase
A
affect ribosome RNA - inhibit protein synthesis - transfer saccharide group
9
Q
Function of Proteases
A
Destroy other proteins - affect pre-synaptic structure
10
Q
Function of adenycyclase
A
affect production of cAMP
11
Q
Mechanism of clostridium difficile
A
- Toxins binding to specific host cell receptors - toxin internalised = endosome
- endosome acidification - pore formation mediated by hydrophobic domain
- GTD release from endosome to host cell cytoplasm - interacts with Rho GTPases
- Rho GTPases inactivation by glycosylation
- Downstream effects within host cell - cytopathic effects or cytotoxic effects
12
Q
Cytopathic effects
A
changing structure of cell
cytoskeleton break down.
decrease cell to cell contact
13
Q
Cytotoxic effects
A
activating production of reacting reactive O2 species - toxic - apoptosis
14
Q
Mechanism of VTEC disease
A
- Bind to receptor Gb3 or Gb4 on host cell membrane
- Bound toxin internalised by receptor mediated endocytosis
- carried by retrograde trafficiking via golgi apparatus to ER
- The A subunit is cleaved off by membrane bound proteases
- Once in cytoplasm A1 and A2 dissociate
- A1 binds to 28S RNA subunit - blocks protein synthesis
15
Q
Pathogenesis of STEC
A
adhere to epithelial cell of gut mucosa.
Bind to glomerular endothelial cells of kidney, CVS, and CNS.
Cause damage to vasculature inducing thrombosis and blocking kidney function leading to uraemic syndrome.
GI to kidney - because kidney has most Gb3
16
Q
VTEC disease symptoms
A
Abdominal cramps, watery or bloody diarrhoea - may not be present.
Haemolytic uraemic syndrome - anaemia, renal failure, thrombocytopenia
Neurological symptoms - lethargy, severe headache, convulsions
17
Q
Structure of endotoxins
A
Only produced by gram negative bacteria.
Lipid A + long fatty acid chain = toxicity of molecule - diverse between bacterial species
Core of rare, uncommon saccharides - relatively stable not diverse
O side chain - interact with immune responses - antigenic highly variable
18
Q
Effects of pro-inflammatory cytokines
A
- increase number and lifespan and activation state of innate immune cells
- increase adhesion molecule and chemokine expression by endothelial cells
- increase acute phase protein - complements, fibrinogen
- cause fever
- cause neutrophils to release NETs made of DNA and antimicrobial proteins - form scaffold for platelet activation.
- cause release of microparticles by activated platelets
- increase tissue factor expression by blood monocytes
19
Q
Sepsis dysregulation
A
Produce ROS - NO and hydroxyl - damage cellular protein, DNA, and impair mitochondria = decrease ATP, cell hibernation = organ dysfunction
Complement activation - change tissue factor expression - increase ROS, enzyme release
Wide spread immunothrombosis - disseminated intravascular coagulation
20
Q
Sepsis resolution
A
Production IL-10 at end of acute inflammatory response = decrease IL-6 interferon and increase receptors that remove inflammatory cytokine
Remove PAMP and DAMP
Damaged cells = apoptosis and engulfment by macrophages
21
Q
Meningococcal sepsis
A
Caused by Neisserio meningitis
LOS instead of LPS - activate and dysregulate immune response
Produce blebs - secreted capsules of the membrane - help hyperactivate immune response - induce sepsis
22
Q
Definition of a virus
A
An infective agent that consists of nucleic molecule in a protein coat.
Is too small to be seen my light microscopy, and is able to multiply only within the living cells of a host.
23
Q
Bacteria
A
Contain nucleic acid covered in protein, have a polysaccharide cell wall and can replicate outside of the cell
24
Q
Prions
A
Are proteins, do not contain nucleic acid and replicate inside the cell
25
Structure of mature HIV-1 particle
Outer envelope consists of lipid bilayer - protruding env spikes.
Inside envelope = Gag proteins
2 genomic RNA strands
26
Virus entry mechanism
Engagement of viral envelope proteins with cell receptors - attach and fuse to the cytoplasm.
CD4 recognises sequence of surface subunit - GP120 of HIV envelope.
Native trimer - CD4 binding - CoR binding, open/uncover transmembrane sub-unit = 6 helix bundle formation - fusion
Helix bundle = push membrane apart so virus can get into cells
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Early phase of HIV-1 infection
Utilise cells microtubule network - move core containing genome into nuclear membrane.
Viral core has capside modifications - determine it gets to the core
Once it gets to the nucleus = reverse transcription
28
Integration of HIV-1
End of viral linear DNA = specific sequences
Integrase enzyme recognises the sequence
Bind viral DNA and cellular DNA - cut cellular DNA and paste the viral DNA into cellular DNA
PRE-INTEGRATION COMPLEX - cellular proteins - LEDGF and TRN-SR2 - recognise cellular DNA and guide viral DNA to it
29
Gene expression HIV-1
- Recruit cellular proteins required for mRNA transcription to viral genome.
- Lef and Nf-kb = promote binding on promoter enhancing region - increase transcription of viral genome.
- 1st thing produced = viral Tat protein - bind to specific viral RNA - increase RNA - preferential treatment.
- Rev produced from viral RNA = + feedback loop = binds to RRE region - increase movement of viral NRA out of nucleus
30
Assembly and release of HIV-1
HIV coordinates production of viral proteins towards the cell surface.
Unspliced viral genomic RNA - dimerises - increase movement to plasma membrane and capsid
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Myristoylation
Myristoylation of glycines in the matrix domain of Gag mediates association with the plasma membrane.
Polyprotein made - myristoylated - transferred using TG101 to cell surface and myrisolation stick it to the cell surface of plasma membrane
32
ESCRT machinery
Hijacked by HIV to perform abscission before viral release.
During abscission - viral proteins pushed out - cut up into individual proteins - protein can reorganise forming capsid structure
Capsid pushed out - extracellular space taking envelope proteins with it
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Abscission
Organisation of proteins and RNA together in new capsid
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Virus pathogenesis - Immunodeficiency
Viruses must evade immune responses - replicate in immune cells so can hide - inhibit immune cell function.
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Direct killing of T cell
Infection of T cells - not all T cells are permissive to HIV replication - 5% permissive
Production of new viruses in permissive cells = activate apoptosis
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Indirect killing of T cell
Non permissive cells
Do not allow virus to replicate
Seen by innate system so does not replicate - pyroptosis
Pyroptosis - inflammation - recruitment of more T cell to site of infection = + feedback.
Uninfected cell undergoing cell death = inflammation lead to cell death
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Oppourtunistic infections of HIV associated pathogens
Inhibition of function - pathogens replicate in virus infected hosts leading to disease
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2 possible routes of infection in HIV associated pathogens
Primary infection
| Reactivation from latency
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Viral latency - Herpes simplex
Virus encounter epithelial cells and replicates - move to dendrites of PNS and CNS - virus can move up and down axon
Virus stay in axon - does not replicate = virus latency
Stimulated to reactivate - virus move down axon and replicate out of productive infection and move into epithelial cells
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Primary infection
HIV infected individual does not have either virus - encounters virus 1st time = infected.
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Reactivation from latency
Primary infection resolved , Infection moves to sites in the host the immune system does not access - virus resides without replicating = latency.
Decrease T cells = reactivation
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Protozoa transmission
Protozoa in human intestine transmitted by faecal oral route
| Protozoa in blood/tissues transmitter by arthropod vector
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Entamoeba histolytica
Amoebic dysentry
| Cause ulcers in large instestine - epithelium
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Giardia lamblia
Diarrhoea with blood
| Common cause in areas with poor hygeine
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Trichomonas vaginalis
Cause infection in genital tracts
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Soil transmitted helminths
Ascaris lumbricodes
Trichuris trichiuria
hookworm - hold onto intestinal mucosa
Enterobius vermicularis - itchy bum in infants
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Filarial parasites
Wuchereria bancrofti - lymphatic filariasis - damage lymphatic system
Loa loa - scleral surface of eye
Onchocerca volvulus - blindness - transmitted by black flies
Drancunculus medinensis - common in africa - contaminate H2O - intestine = ulcers in lower limb - could lead to disability
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Schistoma
Cause disease in intestinal tract, liver and urinary system
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Clonorchis sinensis
Ingestion of contaminated crustaceans - hepatic system = chronic infections
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Fasciola hepatica
Liver and hepatic system - ingest contaminated cloves/vegetation
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Paragonimus
Lung worm infection - ingestion of crustaceans poorly cooked - cough blood
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Tapeworms
Taenia saginata
| Taenia solium
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How is trypanosoma cruzi / chagas disease transmitted
Leads to chagas disease
Bite - feeds and defecates - itch and scratch through the skin and allow access or bug to feed through mucosal membrane - invade cells and asexual reproduction
54
Acute chagas
Tissue damage caused by inflammatory response to parasite in nest of amastigotes in cardiac, skeletal and smooth muscle.
Parasite killing by antibodies leading to innate immune response and Th1 pro-inflammatory cytokines
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Indeterminate chagas
Regulatory immune response characterised by IL-10 and IL-17
| Life long infection - trypanosomes not detectable but + for parasite DNA
56
Chronic chagas
Damage to conduction system of heart or damage to myocardial muscle
Arrhythmia or sudden tachycardia.
Long term damage to muscle leading to heart failure, enlargement of the heart and thin muscular wall.
Chronic inflammatory response to persisistent parasites in muscle and nerve cells
Predominance of Th1 cytokines and CD8+ T cells.
57
Chronic chagas - digestive
Develop in 10-15% of patients
Chronic infections - oesophagus, rectum and sigmoid colon
Damage to PNS - uncoordinated peristalsis - faeces build up in colon = enlargement megacolon
Can lead to ulceration, perforation, obstruction or twisting
58
Transmission of Leishmaniasis
Transmit through vector - transmit a pro amastigote - invade immune cells - develop into amastigote, multiply sexually and burst - increase number.
Cutaneous leishmaniasis - ulcers - present for 3-6 months - scarring
59
Mucocutaneous leishmaniasis
damage to nose tissues - progressive necrotising tissues lesion of nasal tissues = destruction of nose
Mucocutaneous disease associated with strong but inadequate inflammatory response to parasites that have metastasized to mucosa
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Leishmaniasis latency
parasites present long term - regulatory immune response characterised by balance of Th1 and anti-inflammatory response
61
Diffuse cutaneous leishmaniasis
Nodular skin
| Diffuse cutaneous leishmaniasis associated with uncontrolled replication
62
Cercarial dermatitis
Exposure to cercariae - allergic type reaction.
Feature of immune response = granuloma formation - Th2 granuloma - IL4 and IL13
Eggs become organised in granuloma = repairs with scar formation - repeated damage = fibrosis and organ damage
63
Hepato-intestinal schistomiasis
Mansoni and jponicum
Egg released into capillaries - push through capillaries into submucosa by immune response - and pushed into lumen of intestine
Long term damage = cirrhosis, damage to liver and splenomegaly
64
Urinary schistomiasis
Bladder - strong immune response to eggs pushed through mucosa
Eosinophils surround - strong allergic response - haematuria
Changes in bladder - pre-cancer changes - nodular carcinoma of bladder.
Infections and fibrosis - calcified bladder wall
65
Onchocerciasis transmission and effect
Blinding disease
Black fly bites - transmit L3 larvae - migrate to skin - females live in nodules in skin and males go from nodule to nodule fertilising females.
Repeated inflammation to prescence of microflaria = permanent damage in skin and eyes
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Microfilaria in skin
Free of inflammatory infiltrates – strong immune modulation of host – allow parasite to live
Immune regulation delicate – breaks down leading to strong inflammatory response – damages urticaria – bad reaction to microfilaria
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Acute papular onchodermatitis
Papular onchodermatitis = individuals who are chronic infected get periods when immune regulation breaks down leading to microfilaria
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Chronic onchodermatitis
Long term damage to collagen and elastin leading to premature ageing of skin (presbydermia)
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Sclerosing keratitis
Long term damage to cornea from puntate capacities
| Microfilaria in cornea leading to fibrovascular pannus
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Chorioretinopathy
Microfilaria can invade back of eye - affect retinal pigment epithelium - layer of cells needed for metabolic need of neuroretina.
Advanced scar can lead to seeing underlying choroid vessels
71
How do Ticks cause paralysis
Progressive flacidity due to failure of ACh liberation in NMJ.
Ticks produce toxin that blocks the motor nerve fibres
72
Why do some viruses not infect us
They are adapted to non-human hosts
Excluded by surface barriers – innate immunity prevents them from establishing
Adaptive immune response has seen something similar
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Acute infection
Limiting life span - disease symptoms correlate to peak virus load
Huge spectrum of disease and range of outcomes
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Latent infection
Reactivating infection - infection longer and for life - waves of viral activation
Life long infection, controlled by immunity
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Herpes simplex and VZX latency
Virus migrate into sensory neurons - in dorsal root ganglion - IMMUNO PRIVILEGED SITE - establish latent infection in those cells
Viruses move out of transient state - travel back down neuron to specific tissue and eruption of virus
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2 types of persistent infection
Viral levels constantly controlled by active host immunity - occasional change in viral protein = eruption of virus
End of life = immune system can no longer control virus
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Congenital rubella
Virus levels stay up - not controlled by immune system
If infected in utero - baby is immunotolerant and virus continues to replicate = damage neonatal tissue - continues for 2 years after birth
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cytopathic damage of EBOLA
Targets vascular endothelial cells
| Endothelial rupture and release its content
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Cytopathic damage of Influenza A
Targets lung epithelia - destroy ability of cilia to stand/beat to expel lung fluid
80
Cytopathic damage of RSV
Induce syncytia in lung epithelia - cell fusion
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Immunopathology - Hepatitis C
Non-cytopathic
| Associated with extensive liver infiltration of leukocytes - CD8+ cells attach infected cells and destroy them
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Immunopathology - Dengue fever
Most common mosquito borne infection
Increase risk is previous infection with different serotypes.
Antibodies formed in response to infection - not protective against other serotypes can lead to severe diseases due to antibody dependent enhancement
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Antibody dependent enhancement
Antibody bind to virus and phagocytes see virus but does not neutralise - take up virus with Fc receptors = virus get into cells and replicates elsewhere
Get secondary response - complement binding = cell destroyed - increase vascular permeability
84
RSV infections in early life
Unbalanced Th1/Th2 responses - Increase Th2 response and decrease inflammatory cytokine production - Increase IgE production
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Virus isolation in cell culture
Use different cell lines - cells are specialised - slow
Different viruses may give different appearances
Different cell lines may support growth of different viruses
Identify virus using antigen detection techniques or neutralisation of growth
Cell culture + antiviral - look for inhibition of cytopathic effect
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Direct immunofluorescence
Cell associated antigens
Antigen from infected host bound to slide - specific antibody to antigen is tagged to fluorochrome - viewed with microscope with ultraviolet
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Enzyme immunoassay
Free soluble antigens or whole virus
Component reaction is adhered to solid - 3 formats - indirect, direct, and sandwich
Antibody adsorbed to well - antigen binds to antibody - 2nd antibody with enzyme added - chromogenic substrate added - colour change = antigen present
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Immunochromotographic methods
Lateral flow tests - blood or saliva
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Antibody detection by serology - what can serology be used for
Detect antibody response in symptomatic patients
| Determine if vaccination has been successful.
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How is serum produced
produced from processing blood – coagulated with silica and gel trap cellular components
Contains proteins, antigens, antibodies, drugs, and electrolytes
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Diagnosis by antibody detection - serology
Infected by virus - humoral immune response = production of immunoglobulins
Diagnosis made by detection of IgM or by demonstration of seroconversion - switch of IgM to IgG
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Stages of NAAT
1. specimen collection
2. extraction of nucleic acid
3. DNA transcription for RNA viruses
4. Cycles of amplification of DNA target - requires polymerase, dNTPs
5. Detection of amplicons
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Commensal non pathogen
In host - present but not capable of causing disease - E. coli
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Zoonotic non pathogen
In carrier - present but only capable of causing disease in another host
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Commensal opportunist
In host - present and capable of causing disease in host but certain circumstances
96
Non selective media
Blood agar - blood help organisms grow because can release cofactors - like haem or iron
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Semi selective media
DCA, CLED - selection of things that will grow certain things
CLED AND DCA - non lactose fermenting bactera
CLED = red = uses lactose
98
Selective atmosphere
Aerobic culture - cell that are non-aerobe will not grown
| Microaerophilic culture - respiratory pathogens - cell adapted to living in low CO2 - 5% CO2 and can grow
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Phage type
Small virus like particles - attach to certain type orf bacteria - receptors on surface add phage to organism. Phage grows and lysis
100
Virology detecting steps
1. Culture and microscopy
will not grow on plate - intracellular organism - need permissive cell lines.
Will cause a cytopathoc effect when there is a permissive cell line
2. Direct antigen detection
ELISA will look for organism or antibodies against organism - can do dilution series and dilute samples - see how much antibody/virus is present
101
Selective toxicity
Differences between structure and metabolic pathways between host and pathogen
Harm microorganism, not host - usually target microbe - difficult to target viruses as they are intracellular.
Variation between viruses - antivirals work sometimes depending on strain of virus
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Why is it difficult to develop effective non-toxic anti-viral drugs
Viruses enter cell using cellular receptors - IF try inhibiting cellular receptors there would be downstream effect on the cell
Viruses replicate inside cells
Some viruses have a high mutation rate esp. RNA viruses
Anti-virals must be selective toxicity - effect only host cells
103
Amantidine function
Used for influenza - inhibit uncoating of virus by blocking M2 protein needed to uncoat virus - no longer used - was toxic and not very effective
104
Acyclovir mechanism/function
IV/ORAL/TOPICAL - HSV, VZV or prophylaxis - doesn't work well in CMV
Viral thymidine kinase activate drug - phosphorylate ACV - triphosphorylated by cellular guamylate = activated form
Inhibit viral DNA polymerase - chain termination
105
Acyclovir selective toxicity
ACV triphosphate = 30x affinity for HSV DNA polymerase than cellular DNA polymerase
ACV triphosphate - increase polarity = difficult to leave/enter cells - enter cells prior phosphorylation
106
Drugs that can be used for herpes virus
ACYCLOVIR
GANCICLOVIR
FOSCARNET
CIDOFOVIR
107
Ganciclovir function
IV/ORAL for CMV
CMV does not encode thymidine kinase but has UL97
UL97 - inhibit DNA polymerase
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Foscarnet function
IV/LOCAL APPLICATION for CMV
Selectively inhibit viral DNA/RNA - bind to pyrophosphate binding site - allosteric
non-competitive inhibitor
Used because of ganciclovir resistance - mutation in UL97
109
Cidofovir function
IV for CMV
chain terminator - compete with dCTP - target DNA polymerase
Phosphorylated by cellular kinase - diphosphate - active against CMV but toxic - nephorotoxic
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Thymidine kinase mutants
Drugs not needing phosphorylation are still effective
111
DNA polymerase mutants
All drugs less effective
112
Anti HIV drugs
Used in combination - HAART - avoid resistance
1. Anti-reverse transcriptase inhibitors
- Nukes – nucleotide RT inhibitors OR non nukes – allosteric
2. Protease inhibitors – multiple types
3. Integrase inhibitors – POL gene – 3’ encoding for IN allow pro-viral DNA to integrate – block it
4. Fusion inhibitors – block ability of virus to fuse with surface of cell
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AZT - nuke
Synthetic analogue for thymidine - converted to tri-nucleotide = block RT by:
Compete for dTTP and incorporate into DNA causing chain termination
114
Nevirapine - non nuke
Non competitive inhibitor of HIV-1 RT - synergistic with AZT
115
PEP
Post exposure prophylaxis and preventing infection - HIV
Within 72 hours post exposure
take 28 days - 2xNRTIs + integrase inhibitor
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PrEP
Pre-exposure prophylaxis - HIV
| Block transmission - 2xNRTIs
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Consequences of
| Resistance to antivirals
Use single agent leading to rapid development of resistance
| Increase viral load = increase mutation rate = resistance
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Neuraminidase inhibitors
ZANAMIVIR OR OSELTAMIVIR
Virus budding - attached to receptor containing sialic acid - neuraminidase cleave receptor = release virus
Inhibitor - prevent release of sialic acid residues from cell receptor - prevent virus budding
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Treating Hepatitis B
Immunoglobulin - passive immunity and vaccination - treatment = anti-virals NRTIs
DNA virus - but must copy RNA component into DNA component - inhibited by NRTI
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Treating Hep C
Interferon + Ribavirin for 6 months within 1st 2 month exposure
RIBAVIRIN - block RNA synthesis by inhibiting GTP synthesis block IMP to XMP
121
Direct acting anti-virals and hep C
Shorten length of therapy decrease side effects and target virus itself, improve sustained virologic response.
• NS ¾ protease inhibitors – inhibit processing of polyproteins into active proteins – translation
• NS5B polymerase inhibitors – inhibit polymerase
• NS5A inhibitors – block replication, complex formation, and assembly – block viral release
122
COVID-19 antivirals
REMDESIVIR
Prodrug that is metabolised in cells = active nucleotide analogue
Active = inhibit RNA dependent RNA polymerase - incorporate RdRp into growing RNA chain = delayed chain terminator
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What are antibiotics
Natural products of fungi and bacteria - natural antagonism and selective advantage
Most derived from natural products by fermentation then modified to increase pharmacological properties and increase antimicrobial effect
124
Antibiotic associated colitis
Broad spectrum antibiotics damage normal flora = overgrowth of organisms - disrupt the microbiome of gut = ulceration, inflammation, diarrhoea
125
Bactericidal class of antibiotics
Kill bacteria
Used when host defence mechanism are impaired - immunosuppressed
Requried in endocarditis, kidney infection
126
Bacteriostatic class of antibiotics
Inhibit bacteria
Used when host defence mechanisms are in tact
Used in many infectious diseases
127
Beta lactam antibiotics
Base on molecular structure of penicillin and cephalosporins
Structure contain beta lactam ring - active structure in penicillin.
Pass through porin to penicillin binding protein - inhibit peptidoglycan synthesis - structure disrupted - produce autolytic enzyme = bacteria lysis
128
Bacterial targets for common antibiotics
Cell wall synthesis inhibitors
Protein synthesis - prokaryotic ribosomes are different to eukaryotic
DNA and RNA processing - inhibit unwinding
Folic acid synthesis inhibitors
Cell membrane inhibitors - bacteria and norm cell membrane similar = so can be toxic
Antibiotics that produce free radicals
129
Examples of cell wall synthesis inhibitors
Penicillin
cephalosporins
vancomycin
130
Examples of protein synthesis
Different ribosomes - good selective toxicity
50S inhibitor = erythromycin, chloramphenicol
30S inhibitor = tetracycline, gentamicin
131
Examples of DNA and RNA processing
Inhibit DNA gyrase - prevent DNA unwinding
Quinolones - inhibit DNA gyrase - drug selectively inhibits this - prevent replication
Rifampicin - used to treat TB - block DNA directed RNA polymerase - can't make mRNA
132
Examples of folic acid synthesis inhibitors
Block pathways that make tetrahydrofolic acid
Sulphonamids, trimethoprim - 2 enzymes involved in making THFA
Block THFA = block metabolic activity = death
133
Examples of antibiotics that produce free radicals
Metronidazole - work well against anaerobic organisms
| Nitrofurantoin - produce free radicals - used to treat UTI
134
Mechanism of cell wall synthesis inhibition
Vancomycin - recognise 2 alanine at the end of peptide chain - inhibit cross linking
Penicilin and cephalosporin - inhibti enzyme cross linking peptides - act as competitive inhibitors that cross link
135
Mechanism of folic acid synthesis
Humans can't produce own folic acid
Prokaryotic and eukaryotic dihydrofolate reductase are different = selective toxicity
Eukaryotes do not have dihydropteroate synthetase - prokaryotes produce THFA from substrates - so antibiotics inhibit the enzyme = no THFA
136
Methods of antibiotic resistance
```
Drug inactivation
Altered or new target
Efflux pump
Overproduction of target
Metabolic bypass
Intrinsic impermeability
```
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Non genetic mechanism of growth phase - tolerance
Bacteria rapidly replicate - stop growing and form biofilms (ENDOCARDITIS) - stop growing and compromise the function of the organ = tolerance
138
Augmentin/co-amoxiclav
Drug combination - clavulanic acid - bind to and inactivates beta lactamase - allow amoxicillin to work - no anti bacterial activity of its own
139
Vancomycin resistance
Makes D-ala D-lactate - prevent vancomycin from binding because there are missing cross linking reactions.
Acquires genes that encode new metabolic pathway - allow bacteria to make D-ala D-lactate
