Pathogens and Pathogenesis Flashcards
1
Q
How has technology spread disease?
A
Via airplane travel, use of blood banks and suburban sprawl.
2
Q
What are examples of diseases that have spread due to technological advances?
A
Lyme disease = suburban development
E.coli O157:H7 = meat processing plants
COVID-19 and travel
3
Q
What are bioweapons?
A
Highly virulent infectious agents or toxins
4
Q
What are the implications of biowarfare?
A
Inflict massive casualties, rapid onset symptoms, death or temporary incapacitation.
5
Q
What are the implications of Bioterrorism?
A
Widespread panic, disruption of society
6
Q
What is the modern drug discovery process?
A
- Use genomics to identify new targets.
- Design compounds to inhibit the targets
- Alter the compounds to optimize MIC.
- Determine the spectrum of the compound
- Determine the pharmaceutical properties.
7
Q
What are Antibiotics?
A
Secondary metabolites, not essential for microorganism survival, enhances ability to survive
8
Q
How do Protein synthesis inhibitors work?
A
They either interact with the 30S or 50S subunit of the ribosome
9
Q
What are examples of drugs that interact with the 30S subunit of the ribosome?
A
Aminoglycosides and Tetracyclines
10
Q
What do Aminoglycosides do?
A
Cause translational misreading of mRNA.
11
Q
What do Tetracyclines do?
A
Block binding of charged tRNAs to a site on the ribosome
12
Q
What type of agent are Aminoglycosides?
A
Bactericidal - include streptomycin
13
Q
What type of agent are Tetracyclines?
A
Bacteriostatic, include doxycycline
14
Q
What are some drugs that interact with the 50S subunit?
A
Macrolides, Lincosamides, Chloramphenicol, Oxazolidinones, Strepogramins
15
Q
What do Macrolides and Lincosamides do?
A
Inhibit translocation
16
Q
What do Chloramphenicols do?
A
Inhibit peptidyl transferase activity
17
Q
What do Oxazolidinones do?
A
Prevent formation of the 70S ribosome initiation complex
18
Q
What do Streptogramins do?
A
Streptogramin A - Block tRNA binding
Streptogramin B - Blocks translocation
19
Q
What are some examples of RNA synthesis inhibitors?
A
Rifampin and Actinomycin D
20
Q
How does Rifampin work?
A
Binds to beta subunit of RNA polymerase to prevent the elongation step of transcription
21
Q
How does Actinomycin D work?
A
Binds to DNA, prevents the initiation step of transcription
22
Q
Downside of Actinomycin D?
A
It is not selectively toxic
23
Q
Examples of DNA synthesis inhibitors?
A
Quinolones, Metronizadole, Sulfa Drugs
24
Q
Examples of Quinolone drugs?
A
Nalidixic acid, ciprofloxacin
25
How do Quinolone drugs work?
Block bacterial DNA gyrase, preventing DNA replication
26
How does Metronizadole work?
It is non-toxic unless it is metabolised by anaerobes.
27
How do Sulfa Drugs work?
They are PABA analogues (folic acid precursor)
28
What are some drugs that disrupt cell membranes?
Gramicidin and Polymyxin
29
How does Gramicidin work?
Forms cation channels, which ions can leak through
30
How does Polymyxin work?
Destroys cell membranes - detergent like
31
What are bacterial drug targets?
- Cell Wall
- Cell Membrane
- DNA synthesis
- RNA synthesis
- Protein Synthesis
- Metabolism
32
What are the stages of Peptidoglycan synthesis?
1. Precursors are synthesized in the cytoplasm (UDP-NAG and UDP-NAM)
2. They are then carried across the cell membrane by bactoprenol
3. The precursors are polymerised via transglycosylase.
4. The peptide side chains are crosslinked by transpeptides.
33
What are some Beta-Lactam antibiotics?
Penicillins and cephalosporins
34
How do Beta-lactam antibiotics work?
By competitively inhibiting transpeptidases
35
How does Vancomycin work?
Binds ends of peptides and prevents the action of transglycosylases and peptidases.
36
How does Cycloserine work?
By inhibiting the formation of D-ala-D-ala dipeptide precursor.
37
How does Bacitracin work?
By blocking the lipid carrier bactoprenol. Meaning disaccharide subunits do not reach the periplasm
38
What are the classifications of antibiotics?
- Bactericidal and Bacteriostatic
39
What do Bactericidal compounds do?
Kill target organisms, but are only effective if the organism is building a new cell wall.
40
What do bacteriostatic antibiotics do?
Prevent the growth of the organisms.
41
Broad Spectrum
Effective against many species
42
Narrow Spectrum
Effective against few or single species
43
Source of Antibiotics
Most are discovered as natural products that are then often modified by artificial means.
44
How does selective toxicity come into Antibiotic development?
Drug must affect target without being detrimental to host.
Can cause side effects and allergic responses.
45
How are issues with hosts avoided when developing Antibiotics?
They should target physiologies not present in the host. E.g Peptidoglycans, differences in ribosome structure and biochemical pathways missing in humans.
46
When was the importance of antibiotics in treating disease recognised?
1940s
47
What do mechanisms of antibiotic resistance include?
Modifying, destroying and pumping out the antibiotic
48
What tests strain sensitivity to antibiotics?
Kirby-Bauer susceptibility test - disks of antibiotics
49
What test determines MIC?
E-test, gradient of antibiotic on strep, drug must be above MIC in tissue to be effective.
50
What is MIC?
Minimal inhibitory concentration
51
How is MIC determined?
By diluting the antibiotic
52
What does No living colonies on a agar plate in a MIC test indicate?
Mininal lethal concentration, always higher than MIC
53
How does drug resistance develop?
Gene duplications/mutatins and HGT
54
How do bacteria resist antibiotics through target modification?
They can mutate their ribosomal proteins to confer resistance, happens with Streptomycin
55
How do bacteria resist antibiotics through destroying the antibiotic?
Beta-lactamase enzymes destroy penicillin
56
How do bacteria resist streptomycin through enzymes?
Adding modifying enzymes inactivates aminoglycoside antibiotics.
57
How do antibiotics specifically and non-specifically resist antibiotics?
Through pumping the antibiotic out of the cell.
58
How does drug resistance occur?
Antibiotic overuse, overprescription in agricultural settings
59
Who discovered streptomycin?
Selman Waksman
60
Who purified Penicillin?
Florey and Chain
61
What is a virulence factor?
Allows pathogens to cause disease
62
Where can virulence factors be found?
Pathogenicity islands in the chromosome, plasmids or even phage genomes
63
Which pathogen can make proteins to bind antibodies, evading the immune system?
Staphylococcus Aureus Cell Wall protein a
64
How does Staphylococcus Aureus Cell Wall Protein A work?
By binding Fc fragments of antibodies, which cause them to attach upside down, preventing opsonisation.
65
How can pathogens evade the immune system?
Alteration of surface antigens.
Causing apoptosis of phagocytes.
Binding of antibodies.
66
Which pathogens are able to overcome engulfment by phagosomes?
Shigella dysenteriae and Listeria Monocytogenes
67
How do pathogens overcome phagosome engulfment?
By using hemolysin
68
Which pathogens secrete proteins to prevent fusion with lysosomes?
Salmonella, Chlamydia, Mycobacterium and Legionella/
69
Which pathogens use non-pilus adhesins to mediate binding to host tissues?
Streptococcus Pyogenes and Bordetella Pertussis
70
What is Streptococcus Pyogenes' non-pilus adhesin?
M protein, binds to fibronectin
71
What is Bordetella Pertussis' non-pilus adhesin?
Pertactin, binds t integrin
72
What are adhesins?
Any microbial factor that promotes attachment
73
What do most bacterial utilise for attachment to host cells?
Pili
74
What are the main types of pili ?
Type 1 and Type 4
75
What do Type 1 pili do?
Adhere to mannose residues, producing static attachment to host cells. Grow from outer membrane
76
What do Type 4 pili do?
Involved in twitching motility, continually assemble and disassemble, grow from inner membrane
77
What is quorum sensing used for?
Detection of exotoxins made by other cells. Delays toxin synthesis until many bacteria are present.
78
How do bacteria recognise host environments?
Two-component signal transduction, recognising magnesium concentration and pH
79
Biofilms
Specialised, surface-attached communities
80
What sort of protein secretion pathway is Type 1?
Pilus-like
81
What sort of protein secretion pathway is Type 2?
Syringe like
82
What sort of protein secretion pathway is Type 4?
Conjugation system like
83
What are the 5 categories of protein exotoxins?
1. Membrane disrupters
2. Protein Synthesis disrupters
3. Secondary messenger pathway disrupters
4. Superantigens
5. Proteases
84
What type of toxin is only made by Gram negative bacteria?
Endotoxin
85
What are two types of disease protection and prevention?
Vaccines and Herd Immunity
86
What is herd immunity?
When a large % of the community is vaccinated
87
What can vaccines be made from?
Killed/attenuated organisms or purified components of infectious agents
88
How does Type 4 secretion work??
Similar to conjugation pilus, secretes proteins only or proteins+DNA.
Secretes from cytoplasm or periplasm
89
Example of a pathogen that uses Type 4 secretion?
Bordetella pertussis
90
How does Type 3 secretion work?
Molecular syringe, inject proteins from cytoplasm into the host cell.
Genes for proteins are on pathogenicity islands.
Base of the needle complex spans the Inner membrane and outer membrane.
91
Which pathogens possess Type 3 secretion systems?
Salmonella, Yersinia and Shigella.
92
How does Type 2 secretion work?
Pilus can extend and retract. Proteins to be secreted from the periplasm are folded then secreted
93
How do endotoxins get out of bacterial cells?
Protein secretion systems, tend to use mechanisms already present in the bacteria.
94
How do Endotoxins work?
Present in LPS of outer membrane, Lipid A released as bacteria die, causing massive cytokine release. Triggers fever, shock and death.
95
What is alpha toxin prodced by?
Staphylococcus aureus
96
What does hemolytic alpha toxin do?
Breakdown iron components, uses them for survival and metabolism. Forms a transmembrane seven member pore in target cell membrane.
97
How does S.Aureus damage cellular membranes?
Through its alpha toxin. Causes release of haemoglobin from RBCs.
98
How does Shigella inhibit protein synthesis?
Shiga toxin attaches to ganglioside Gb3, entering the cell and cleaves 28s rRNA
99
How does E.coli activate secondary messenger pathways?
E.coli Heat stable toxin activates guanylate cyclase of intestinal epithelial cells; which causes osmotic imbalance.
100
What is Cholera toxin's mode of action?
1. Toxin complex binds ganglioside GM1 on host membrane lipid rafts.
2. Toxin is endocytosed.
3. Phagosome migrates to endoplasmic reticulum.
4. A1 subunit is removed from the B subunits and exported to the cytoplasm.
5. The A1 peptide attaches an ADP ribose to an amino acid which regulates adenylate cyclase.
6.Cyclic AMP rises and activate ion transport, causing electrolyte imbalance.
7. Water from the cells follows the ions, causing diarrhea.
101
What are examples of ADP-ribosylating toxins?
Diptheria and Cholera
102
What produces Diptheria toxin?
Corynebacterium Diptheriae
103
What produces Cholera toxin?
Vibrio Cholerae
104
How does Cholera toxin work?
Ribosylates to overactivate adenylate cyclase
cAMP activates ion transport; water follows
Uncontrollable diarrhea
105
How does Diptheria toxin work?
Ribosylates elongation factor 2
Blocks ribosome function; cell dies.
Forms psuedomembrane over trachea.
106
How does the A unit of AB toxins work?
Has toxic activity through ADP ribosyltransferase
107
How does the B unit of AB toxins work?
Binds to host cell, delivers A subunit.
Often 5 B subunits to form a pore for A entry.
108
Which pathogens use AB toxins?
Shiga, Diptheria, Cholera
109
How does tetanus toxin work?
Through retrograde movement. Toxin enters nervous system at the neuromuscular junction, travels against signal flow to inhibitory neurons.Cleaves VAMP protein involved in exocytosis, blocking GABA release.
110
What do exotoxins do?
Subvert host function
111
Why type of toxin is tetanus toxin?
Protease
112
What type of toxin is Staphylococcus Aureus' TSS toxin?
Superantigen
113
What type of toxin is E.coli's Heat stable toxin?
Secondary messenger pathway disrupters
114
What is epidemiology?
Examines the distribution and determinants of disease frequency in human populations
115
What is an epidemic
High disease frequency over a short period
116
What is a pandemic?
Epidemic that occurs over a wide geographic area
117
How are safety levels monitored in labs?
Biological Safety Levels
118
What is the most severe BSL ?
BSL IV, complete isolation
119
How is PCR used to detect pathogens?
Through amplification of small DNA fragments, can identify tiny numbers of bacteria.
120
How are bacteria further categorised after PCR?
Restriction analysis to indicate strain
121
How are gram-negative bacteria detected?
Analytical profile index strips
122
What are issues with growing organisms on plates?
Inability to obtain pure cultures
Passage in the lab can lead to attenuation
SOme diseases are caused by combinations of microbes
Different strains of the same species can have different pathogenic properties
123
What are the steps to Koch's postulates?
- Plate blood, streak it, forming singular colonies.
- look for causative agent
- Culture, reinject mouse and plate again
124
How do we identify pathogens?
1. Symptoms
2. Isolation and growth of microorganism
3. Reinfection
4. Pattern of infection
5. Biochemical/Metabolic properties
6. Site of infection
7. Drug sensitivity
125
What is a physiochemical host defence mechanism?
Skin
126
Examples of pathogens that can infect via Fomites?
- MRSA and Streptococcus Pyogenes
127
Examples of pathogens that can infect through accidental and direct pathways?
Staphylococcus epidermis (skin) and neisseria meningitides (saliva)
128
Example of a pathogen that can infect through vertical transmission?
Treponema Pallidum (Syphillis)
129
What does verticla transmission mean?
From parent to child
130
What does accidental transmission mean?
Host who is not usually a part of the infectious cycle
131
What does horizontal transmission mean?
From one member of the species to another.
132
What are primary pathogens?
Cause disease in healthy hosts
133
What are opportunistic pathogens?
Cause disease only in immunocompromised patients
134
What is virulence?
A measure of the severity of a disease
135
Examples of skin and soft tissue infections?
- Boils; scalded skin syndrome (staphylococcus aureus)
- Necrotising Fascitis (Streptococcus pyogenes)
136
Examples of respiratory tract infections?
- Pneumonia
- Tuberculosis
137
Examples of GI tract infections
- EHEC - enterohemorrhagic E.coli
- Salmonella
-Shigella
- Helicobacter pylori
138
Example of a pathogen that causes UTIs.
Uropathogenic E.coli
139
Examples of systemic diseases?
- Yersinia Pestis and Borrelia Burgdorferi (Lyme disease)
140
What are the Clostridium toxins?
- Botulin and Tetanus
141
How does C.Botulinum work?
It is an anaerobe that grows in canned foods.
Spores survive unless it is autoclaved.
Toxins block the release of acetylcholine = flaccid paralysis
142
How does C.Tetani work?
- Anaerobe, grows in puncture wounds.
Blood flow becomes interrupted, tissue becomes anaerobic.
Blocks release of GABA, inhibitory transmitter.
Causes spastic paralysis
143
What is Meningitis?
Infection of meninges of the brain.
Bacteria crosses blood-brain barrier
144
How does Neisseria Meningitidis cause Meningitis?
- Thick capsule
- crosses from the capillaries into the cerebrospinal fluid
Once in the meninges, it is difficult to treat
145
What species caries Borrelia Burgdorferi?
Ixodes Sacapularis tick
146
What are the 3 stages of Lyme disease?
Rash, Joint muscle nerve pain, arthiritis.
147
What does yersinia in the lymph nodes cause?
Bubonic Plague
148
What does yersinia in the blood cause?
Septicemic plague
149
What does inhaled yersinia cause?
Pneumonic Plague
150
What is Endocarditis?
Inflammation of the hearts inner lining
151
What is Septicemia?
Presence of microbes in the blood.
152
What is Streptococcus Mutans caused by?
Dental procedures.
Grows on damaged heart valves, forming biofilms.
DIfficult to treat
153
How does Neisseria Gonnorrhoeae cause disease?
Binds to CD4 T cells, inhibiting. T cell activation.
Women are asymptomatic reservoirs
154
How does Chlamydia cause disease?
Intracellular lifecycle, reticulate bodies.
Live within immune cells
155
What are the types of Syphillis?
Primary - Chancre at the site of the infection
Secondary - Generalised rash
Tertiary - effects on heart and CNS
156
Uropathogenic E.coli
- Invades bladder up from the urethra
- Causee 75% of UTIs
157
How do active infections of the urinary tract occur?
Descending or ascending infection from the kidneys or infection from urethra migrates.
158
What is the most frequent cause of diarrhea?
Campylobacter Jejuni
159
What is most food poisoning caused by?
Staphyloccocus Aureus
160
What causes Gastric ulcers?
Helicobacter Pylori
161
How does Helicobacter Pylori cause stomach ulcers?
Secretes urease, causes urea to convert to ammonimum ions that neutralise stomach acid.
This allows the bacteria to burrow into protective mucus layers.
162
EHEC
Enterohemorrhagic
163
ETEC
Toxigenic
164
EAEC
Aggregative
165
What does EIEC produce?
Shiga toxin
166
How is knowledge of a patients history vital?
Can give answers to where disease came from.
Hobbies/Travel/Occupation etc
167
Which pathogen is linked to farmers?
Q fever caused by Coxiella Burnetti
168
Which pathogen is linked to hunters?
Francisella Tularensis
169
Gram positive bacteria have:
Thick Peptidoglycan layer
170
Gram negative bacteria have:
Two lipid bilayers with a think peptidoglycan layer between them
171
What does the Mucin layer do?
Lysozymes digest bacterial peptidoglycans.
sIgA prevents bacterial attachment to mucosal cells.
Lactoferrin binds iron to prevent bacterial growth
172
What is the major cause of many nosocomial infections?
MRSA
173
What is the primary defense against respiratory issues?
Mucociliary escalator
174
First lines of defence against disease:
1. Skin
2. Saliva
3. Tears
4. Mucus lining
5. Stomach aciid
6. Good gut bacteria
175
What causes colitis?
Clostridium dificile
176
What type of parasite is Blastocystis?
Gastrointestinal
177
What are the four cellular forms of blastocystis?
- Vacuolar
- Granular
- Cyst
- Amoeboid
178
What are Blastocystis cells?
Strictly anaerobic, cells die within minutes when exposed to oxygen
Deflate like balloons.
179
What phenotype do some blastocystis cells show when exposed to oxygen?
"Medusa head", membrane extrusions can be seen around the cell.
180
What is the definition of Stramenopiles?
Having flagellar hairs
181
Why is blastocystis categorized as a stramenopile if it doesn't have flagellum?
Must have arisen from a related member
182
How many different Blastocystis subtypes are there?
At least 30
12 in humans
Vary in prevalence in different hosts
183
How is Blastocystis transmitted?
Mainly fecal-oral. Zoonotic, but also located in water and soil.
184
What vary in the different subtypes of Blastocystis?
DNA base composition, size of the genome, number of genes and number of introns
185
What is Blastocystis?
Common gut commensal with reduced abundance in IBD cases.
186
What is the hygeine hypothesis?
When the body's immune system is no longer challenged by infectious organisms, making it more likely to be inappropriately stimulated. This leads to increased susceptibility to allergies and autoimmune diseases.
187
What is Diabetes mellitus incidence related to?
Corresponding declines in helminth infections
188
Parasites that are used to treat medical conditions?
- Helminths
- Larvae
- Leech
- Malaria
189
What type of mitochondria does Blastocystis have?
Similar to Anaerobic mitochondria/Hydrogenosome
190
What do Blastocystis carriers have?
- Lower BMI
- Absence of GIT issues
- Higher bacterial richness and diversity
191
What is cryptosporidium related to?
Plasmodium
192
What does cryptosporidium lack that plasmodium retains?
Apicoplast
193
Why is Cryptosporidium so concerning?
No drug currently for treatment
194
What is cryptosporidium associated with in children?
Stunted growth
195
Why is cryptosporidium such a difficult organism to study?
There is no culturing system for it
196
What makes cryptosporidium so infectious?
Oocysts resistant disinfectants
Low infectious dose
Many sources and transmission routes
197
Who is at risk of Cryptosporidium infection?
- Contaminated water/food intake
- Travel to less industrialised countries
- Recreational water users
- Contact with farmed animals
- Childcare settings
- Contact with other ill people
198
Who bears the greatest burden from cryptosporidiosis?
- Immunocompromised
- Young Children
- Malnourished children
199
What are the clinical concerns of cryptosporidiosis?
1. Lack of treatment regimen
2. Long term health effects
3. Potential for large scale outbreaks
200
Symptoms of cryptosporidiosis?
Gastrointestinal symptoms, diarrhoea, abdominal pain, vomiting, fever, anorexia
201
How have Cryptosporidium host-pathogen interactions been studied?
Metabolomics, Proteomics and microscopy. Identification of metabolites.
202
Which metabolic pathways influence host metabolism upon infection with Cryptosporidium?
- Amino Acid biosynthesis
- Sugar metabolism
- CoA biosynthesis
- Taurine biosynthesis
203
Which group do Trypanosomes and Leishmania fall under?
Kinetoplastids, which are derived from Euglenozoa
204
What does Trypanosoma Brucei cause?
Sleeping Sickness
205
What are the 3 important kinetoplastid diseases?
Trypanosoma Brucei/Cruzi and Leishmania
206
What are the two types of Trypanosoma Brucei?
Gambiense and Rhodesiense, split based on vector transmission
207
Why do Trypanosomas utilise Antigenic variation?
To maintain chronic infection and to constantly evade the immune system
208
How do Trypanosomes vary their antigens?
They alter their surface proteins which cause waves of parasitemia.
209
How many genes and pseudogenes encode the variable surface glycoproteins?
More than 1,000, change VSGs every couple of days
210
Why do Trypanosomes possess both genes and pseudogenes?
To avoid selective pressures, allows them to adapt better as a single celled organism
211
What does Trypanosoma Brucei Gambiense affecr?
CNS, slow onset but chronic trypanosomasis
212
What does Trypanosoma Brucei Rhodesiense affect?
Widespread organ damage, fast onset acute trypanosomasis
213
What is the vector for Trypanosoma Brucei?
Tsetse Fly
214
What happens in the Human lifecycle of Trypanosomas?
1. Tsetse fly takes a blood meal
2. Infects bloodstream, and converts into bloodstream trypomastigotes, which carry to other sites.
3. These multiply via binary fission in various bodily fluids.
215
What happens in the Insect lifecycle of Trypanosomas?
1. Tsetse fly takes an infected blood meal from human
2. Bloodstream trypomastigotes transform into procyclic trypomastigotes in their midgut.
3. These multiply via binary fission
4. When procyclic trypomastigotes leave the midgut they become epimastigotes.
5. These multiply in the salivary glands and transform into metacyclic trypomastigotes.
216
What happens to the physiology of Trypomastigotes in human blood?
They become stumpy, due to the high glucose levels
217
What is characteristic about Trypanosome cells?
- Huge Flagella
- Kinetoplastids and Glycosomes = both not present in humans
218
What is the glycosome?
Unit for Glycolysis in Trypanosomes
Allows for high glycolytic activity
219
What is the kinetoplast?
Single Mitochondrion
Has compact mitochondrial DNA = makes up about 25% of DNA content of the cells
220
What is Kinetoplast DNA composed of?
Mini Circles - 5-10,000 copies
Maxi Circles - 20-50 copies
221
What does Mini circle kDNA do?
Guide RNAs to decode maxi circle genes
222
Why does Trypanosomas have such a complex Mitochondrial genome?
Protects against selective pressure
It is energetically costly
223
What is the insect stage of Trypanosomas reliant on?
The mitochondria for ATP
224
How is ATP generated in Trypanosoma?
Via ETC and proton pumping ATPase, partly encoded by mitochondrial DNA
225
What is critical for proton translocation in Trypanosomas?
FoF1 ATP synthase
226
What is key for ATP export in Trypanosoma?
ADP/ATP translocase, exports ATP in return for ADP.
Flagella requires large amont of ATP
227
What is unique about the ETC in the bloodstream stages of Trypanosomas?
They lack complexes 1,2, and 3.
Means no proton gradient is formed = no energy
FoF1 is functioning in the opposite direction.
Takes ATP and exports it to maintain the H+ gradient
228
What are two types of Trypanosomes that occur in other vectors?
- Evansi - surra
- Equiperdum - horses/camel
229
What is different about T.Evansi and Equiperdum?
They are Dyskinetoplastic (no kinetoplast) and are transmitted without an insect lifecycle
230
What does Evansi and Equiperdum being Dyskinetoplastic mean?
Lack of kDNA, no functional mitochondrial gene expression.
Cannot produce ATP via oxidative phosphorylation
Reliant on other methods of trnasmission
231
What has a lack of kinetoplast shown in lab strains?
Trypanosomes are easier to mutate, they become more susceptible to drugs.
232
What have experiments that knockout the ADP/ATP carrier in Trypanosomes shown?
They are able to discard functions and stay a live, maybe not the best drug target as they survive.
233
What could have been the reason for superior mutations in Evansi and Equiperdum?
The lack of tsetse as a host may have prompted them or the fact that these mutations occured may have avoided the use of tsetse
234
What is a drug that targets Kinetoplasts in Trypanosomes?
Acriflavine
235
What is a concern about Trypanosomes?
Single nucleotide changes can make trypanosomes completely independent of their kDNA and gene products --> may make kinetoplasts a less worthy drug target
236
What is Plasmodium a type of?
Apicomplexa, obligate parasite
237
What is the apical complex of Plasmodium formed of?
Preconocoidal Ring
Polar ring
Conoid
Microtubules
238
What is the function of the Apical complex?
It is an invasion mechanism, works to penetrate blood cells/epithelial cells. Secretes proteins to manipulate cells
239
What does Plasmodium use as a vector?
Anopheles
240
What is the most deadly Plasmodium species?
Plasmodium Falciparum
241
What does Plasmodium require to mate and mature into sporozoites?
10-18 days at a temperature of >21 degrees
242
What is an unusual location for Plasmodium replication?
Car tyres, provides a humid environment due to collection of rain water
243
What is efficacy of Malaria transmission dependent on?
The vector
244
What are the majority of Malaria carriers?
Female Anopheles due to the presence of hormone 20-E
245
What does the presence of 20-E mean in female mosquitos?
Increased longevity, increased blood feeding preferences, and increased lipid transporters which assist the development of Plasmodium by reducing the parasites immune system.
246
What are typical symptoms of malaria?
Fever, Chills, Nausea, Sweat, Headaches, Vomiting and Diarrhoea
247
What is the worst type of malaria and what typically causes it?
Complicated Malaria and Plasmodium Falciparum
248
What are the symptoms of complicated Malaria?
Severe Anemia, Organ damage, Coma and Hypoglycaemia. Associated with higher levels of mortality
249
What are the 3 lifecycles of malaria?
Insect, Liver and Human
250
What is the process of Plasmodium infection in humans?
1. Mosquito infects human with sporozoites
2. These form merozoites in the liver which explode
3. Triggers asexual cycle in which Plasmodium forms rings in RBCs
4. Leads to sexual differentiation into gametocytes
5. These then go on to infect other vectors through blood meals
251
Why is it effective to know about a parasite's lifecycle?
We can target drugs/vaccines to it
252
What varies between different plasmodium species?
Mechanisms/Factors used to invade host cells
253
What has recent research shown about Plasmodium transmission?
Mononemes are excreted in the bloodstream from merozoites - encoded by the parasite
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What do Mononemes do?
They are secretory organelles which manipulate cellular architecture of RBCs. They are able to hijack host cell mitochondria
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What is significant about Apicoplasts in Plasmodium?
If you deplete = Parasites die, essential for survival.
They are present in all life stages of the parasite, provide a good/easy drug target
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What is the function of Apicoplasts in Plasmodium?
They fuel metabolic pathways of the Organelle
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What is unique about mitochondria in Plasmodium?
They only have one and it is more active in the insect host
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What is a drug used in Malaria-stricken countries?
Atovaquone, resistance has been shown in insects but prevents transmission
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How does Atovaquone prevent transission of Malaria?
Parasites with atovaquone resistant CytB genes do not generate viable progeny by self fertilisation = lower transmission.
Lower prevalence of mosquitos that are not susceptible to the drug.
