Viruses and anti-viral drugs-3 Flashcards
Important steps in virus life cycle (8 steps)
- Virus adsorption (fusion of virus membrane with host membrane)
- Virus penetration
- Uncoating
- Integration of virus’ genome (transcription/translation)
- Genome replication
- Viral protein synthesis - protease action on polypeptides
- Assembly
- Release of virions- by lysis- using neuraminidase
A few anti-viral drug classes
Fusion inhibitors Channel blocking inhibitors Nucleotide/nucleoside polymerase inhibitors Non-nucleoside RT inhibitors Protease inhibitors Neuraminidase inhibitors
How is a virus uncoated?
Acidification of viral capsid coat
Involving H+ proton channels (MI/M2)
What do nucleotide/nucleoside polymerase inhibitors do?
prevent RNA synthesis
incorporate themselves in RNA polymerase= prevent nucleotides being added to RNA strand
What do non-nucleoside reverse transcriptase inhibitors do?
prevents RNA being converted to DNA (so stops HIV replicating for example)
Role of protease inhibitors
Prevents assembly of viral proteins= no viral protein synthesis
Nucleotide vs nucleoside
A nucleoside consists simply of a nitrogenous base and a five-carbon sugar (ribose or 2’-deoxyribose) whereas a nucleotide is composed of a nitrogenous base, a five-carbon sugar, and one or more phosphate groups
Where is hemagglutinin and neuraminidase found?
2 glycoproteins found on the surface of influenza
What does hemagglutinin do?
allow adhesion of influenza virus to host cell and allowing endocytosis of virus into host cell
What does neuraminidase do
Cleaves sialic acid on surface of influezna
Allows budding of virus- released from cell and spread to infect nearby cells
Purpose of proteasomal degradation of virus in cell?
allows release of genome
RNA sense strands that are then converted to +RNA sense strands= for protein synthesis
Name of 2 neuraminidase inhibitors
Oseltamivir
Zanamivir
What do we need to consider for treatment for influenza?
1) Is it complicated/uncomplicated?
2) Are they severely immunosuppressed?
3) Are they healthy/in risk group (e.g asthma/ CDV problems)
4) Does virus have resistance to drug (oseltamivir)?
We must try limit use of oseltamivir/zanamivir to reduce resistance of viral strains to drug as influenza undergoes frequent simple point mutations= antigenic drift
2 types of bacterial toxins
Endotoxins (part of gram neg bacterial cell wall=LPS)
Exotoxins (released from cell once it dies)
Types of exotoxins
Enterotoxins
Neurotoxins
Cytotoxins
What are enterotoxins?
Type of exotoxin
Produced in intestines
Activate adenylyl cyclase and guanylate cyclase
Causes food poisoning
What are cytotoxins?
Destroy and kill cells Macrophage cytotoxin= damages macrophages Activate thiols (thiols=cytolysin)- cause lysis of cell Vacuolating cytotoxin= induced in gastric epithelial cells= gastric tissue damage
What are phenol soluble modulins?
amphipathic peptides produced by staphylococci
have multiple functions in pathogenesis
What do toxins released by Staphylococcus alpha and PSM do?
Prevent lysosome fusing with phagosome once phagocyte engulfs bacteria= phagosome
so lysosome can’t bind to phagolysosome
Allows bacteria to escape phagosome and go into cytoplasm
This allows bacteria to replicate in the cell (intracellularly)
What do toxins of PSM do?
- PSM toxins target cohabiting bacterial species within established niches, aiding in competition for resources and competitive exclusion of nonkin isolates
- PSM toxins have surfactant properties:
Allows bacteria(S.aureus) even without flagella to move across surface (e.g S.aureus don’t have flagella) using surfactant molecules
What else do toxins released by staph.aureus do?
Form toxins to produce spores= involved in biofilm formation
Biofilm= microorganisms irreversibly attach to and grow on a surface and produce extracellular polymers that facilitate attachment and matrix formation (Where bacteria grow)
Spores allow nutrients to enter
What is bacillus cereus?
Gram-positive rod-shaped facultatively anaerobic beta-hemolytic, spore forming bacterium commonly found in soil and food Cause infection and toxin based disease
How many toxins does bacillus cereus produce and where?
3 in small intestine
1 form in food
What are the 3 toxins bacillus cereus produces in the small intestine?
- The three component enterotoxin haemolysin BL (HBL)
- The three component non-haemolytic enterotoxin (NHE)
- Single component enterotoxin cytotoxin K
Clinical features of bacillus cereus in small intestine- incubation period? symptoms?duration of symptoms?foods involved?
Incubation period= 12-24 hours
Symptoms- watery diarrhoea, abdominal pain
Duration of symptoms- 12-24 hours
Foods- meat, soups, rice, milk
What toxin does bacillus cereus produce in food?
Cereulide (cyclic peptide)
Clinical features of bacillus cereus in food- incubation period? symptoms?duration of symptoms?foods involved?
Incubation period- 30 mins-5 hours
Symptoms- Nausea, vomiting, malaise
Duration of symptoms- 6-24 hours
Foods- rice, pasta, noodles, pastry
What does it mean if patient experiences all symptoms?
All 4 toxins are produced by bacillus cereus
What is a parasite?
an organism that lives on or in a host organism and gets its food from its host- causes harm to host
eukaryotic- can be uni/multicellular
3 main classes of parasites?
Protozoa
Helminths
Ectoparasites
Definition of a host
A living cell invaded by or capable of being invaded by an infectious agent (bacteria/virus)
Definition of an intermediate host?
An organism that supports the immature or non-reproductive forms of a parasite
Definition of a reservoir host?
Animal/species that is infected by parasite
serves as a source of infection for humans or another species
Aids in transmission of parasite
Definition of a vector
an organism that does not cause disease itself but which spreads infection by carrying pathogens from one host to another
What is a trophozoite?
protozoan in its early growing stages
active
reproductive stage of the protozoans that feeds on the host
Whats a cyst?
dormant stage of the protozoans
resist unfavourable environmental conditions
formed in stool, like a spore
produced asexually
Whats a oocyst?
thick–walled cell
present in the life cycle of protozoa that contains a zygote of protozoa within it
Meaning of zoonotic?
A disease that can be transmitted from animals to people
A disease that normally exists in animals but that can infect humans e.g anthrax
3 conditions caused by parasites
Scabies
Lice
Bed bugs
What is scabies?
Caused by mites
Burrow’s under host’s skin
Inflammatory response causes symptoms
Cause intense itching as mites lay skin
What is lice?
Small, wingless, six legged insects
Have claws to grasp hair
Live lice lay louse eggs (nits) onto scalp of host
What are bed bugs?
Commonly found in communal sleeping environments (hotels/dorms)
Infest mattresses and bedding
Most active night when they bite individual
What are helminths?
Also known as parasitic worms (tropical)
Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract
Examples of helminths
Human whipworm (in intestine) Pinworm (in intestine)
Habitat of parasites
Duodenum and upper jejunum
Morphology of parasites? (2 forms)
Trophozoite- shaped like a leaf
Cyst- oval, found in stool, double celled wall, diagonal axostyles (sheets of microtubules)
What is giardia?
Parasitic microorganism
Colonises and reproduces in small intestine
Life cycle of giardia
- Transmission by- faecal/oral, poor hygeine contaminated h2o/food
- Excystation- parasite escapes from cyst once it enters host by H+ ions and cytokinesis
- Multiplication-binary fission
- Pathogenesis- toxins
- Encystment
- Cyst metabolism- O2 uptake
- Cyst viability- temperature
What is cyst wall made of?
Protein/carbohydrate
Resistant to some disinfectants
How do cysts cause damage to host?
Cysts can cause diarrhoea and change gut epithelia= less absorptive so parasite can gain more nutrients
Cysts consume arginine- immune cells need arginine to make nitric oxide= anti parasitic
So depriving them of this amino acid= reduces action of immune cells
How are parasites diagnosed?
- Gelatin capsule/Enterotest: capsule attached to string detects presence of parasites
swallowed and left in place
After about 4 hours, the gelatin capsule is pulled out of the stomach by the string. Any bile, blood, or mucus remaining on the string is examined under the microscope for cell types and segments of parasites or eggs - Stool sample- examine stool sample under microscope for parasite
- Duodenal aspiration: Smear of duodenal fluid aspirate is an exam of fluid from the duodenum to check for signs of an infection
Treatment of parasites?
Metronidazole/Tinidazole
inhibits protein synthesis by causing loss of helical structure of DNA
Metronidazole- antibacterial and antiprotozoal
Binds to DNA= DNA damage
Prevention of parasitic diseases?
Personal hygiene
avoid food and water contamination
drink safe water
What is cryptosporidium?
microscopic parasite that causes the diarrheal disease cryptosporidiosis
Life cycle for cryptosporidium
1) Sporulated oocysts, containing 4 sporozoites, are excreted by the infected host through faeces
2) Transmission of Cryptosporidium= mainly through ingestion of faecally contaminated water (e.g., drinking or recreational water) or food (e.g., raw milk) or following direct contact with infected animals or people
3) Following ingestion by a suitable host image , excystation occurs (a)
4) The sporozoites(oocysts) are released and parasitize the epithelial cells (b,c) of the GI tract (and possibly the respiratory tract)
5) In these cells-the parasites undergo asexual reproduction (d,e,f)
6) Then sexual reproduction (g and h)= microgamonts= male, female= macrogamonts
7) Fertilisation of microgamonts and macrogamonts
8) Oocysts develop and sporulate in the infected host
9) Zygotes give rise to two different types of oocysts (thick-walled and thin-walled)-Thick-walled oocysts are excreted from the host into the environment
Oocysts are infectious upon excretion, thus enabling direct and immediate faecal-oral transmission
Incubation period of cryptosporidium
7 days
Symptoms of cryptosporidium infection
Watery diarrhoea Weight loss Abdominal pain Nausea Vomiting Chronic and more severe in immunocompromised patients
What is the main site that cryptosporidium infects?
Small intestine (but can be in digestive organs, lungsand possibly conjuctiva)
How is cryptosporidium identified in the lab?
Acid-fast staining- differential stain used to identify acid-fast organisms, acid-fast organisms are highly resistant to disinfectants and dry conditions
Stool sample
Greater sensitivity and specificity= immunofluorescence microscopy followed by enzyme immunoassays and PCR
Treatment of cryptosporidium infection
Fluid and electrolyte replacement
Nitazoxanide- treatment of diarrhoea
Treatment of cryptosporidium in patient with AIDS
Anti-retroviral therapy= improves immune response
and reduces oocyst excretion = decrease diarrhoea associated with cryptosporidiosis
What is trichomonas vaginalis?
infection caused by a tiny organism (a living cell) called Trichomonas vaginalis
It can infect the vagina
Sexually transmitted
Only trophozoite (has flagella)- no cyst form
Females- discharge from vagina
Males= asymptomatic
Diagnosis of trichomonas vaginalsis?
Presence of trophozoites in wet films/giemsa stained smear
Treatment of trichomonas vaginalsis?
Metronidazole
What parasite causes malaria?
Single celled parasite- plasmodium
4 types of plasmodium that infect humans?
Plasmodium falciparum (main one)
Plasmodium vivax
Plasmodium malariae
Plasmodium ovale
Life cycle of malaria
1) Mosquito injects malaria parasite into human
2) In liver: sporozoites invade liver cells
- After 10 days= sporozoites develop into merozoites
- Merozoites released into blood
3) Merozoites invade red blood cells
4) After 48 hours= merozoites released from RBC into blood
5) Sexual forms of parasite= gametocytes form in RBCs over 10 days
6) Gametocytes taken up by mosquito from human
7) Gametocyte mature into gametes
8) Gametes form zygote-oocyst by sexual reproduction-containing thousands of sporozoites
Sporozoites migrate to salivary gland
How is malaria controlled?
- Vaccine
- Bednets- protective barrier, treated with insecticide to kill mosquito
- Chemotherapy
What drugs prevent merozoite and trophozoite formation?
Antifolates- proguanil, pyrimethamine
What drugs prevent merozoite formation?
Atovaquone
What drugs prevent formation of trophozoite and gametocyte?
What drugs prevent formation of trophozoite and gametocytes?
Artemisinin
Quinolones- chloroquine, mefloquine
Antibacterials= tetracycline, clindamycin, fluoroquinolone
Why dont drugs always work?
- Wrong diagnosis
- Incorrect choice of drug
- Poor quality drugs
- Resistance to drug
- Suboptimal absorption (mal-absoprtion)
Mefloquine MOA- Malaria
Anti-malarial Effective against plasmodium falciparum produce swelling of the Plasmodium falciparum food vacuoles Forms toxic complexes Damages membrane of plasmodium
Artesunate MOA- Malaria
Inhibit protein and nucleic acid synthesis of Plasmodium parasites during all erythrocytic stages
