Week 2 Flashcards
How pathogens have shaped human evolution
Shaping our immune system, learning to fight infections
Invasion of the genome-endogenous retroviruses, profoundly influenced the human genome
Categorising pathogens
Pathogens that cause infectious disease are classified depending effectively on how deadly they are
4 bio-safety containment levels BSL:
-BSL-1: unlikely to cause disease
-BSL-2: can cause disease but unlikely to spread in the community
-BSL-3: can cause disease and spread but treatments available
-BSL-4: the deadliest. Will cause serious disease, will spread and generally no treatments
Current issues
The rise of anti microbial resistance:
-making simple infections difficult to treat
-AMR bacteria killed more people in 2019 than HIV/AIDS and malaria combined
Epidemics and pandemics:
-in the last 10 years- major viral outbreaks
-COVID-19, Mpox, Ebola, Zika, influenza
More outbreaks will happen
Smallest to largest microbes
Prions
Viruses Host required
prokaryotes: bacteria
Eukaryotes: fungi, parasites (trypanosomes)
Prions
A mutant protein= prion protein
-causes other normal proteins to fold abnormally (spongiform encephalopathy)
-aggregates of abnormal proteins in the brain= degeneration
Prion protein (PrPc)= normal protein
-expressed in neuronal tissues and tonsils
PrPsc= abnormal protein
-sc=scrapie
Diseases caused by prions:
-creutzfeldt-Jakob disease CJD
-Kuru
-mad cow disease or vCJD
CJD- pathology and transmission
100% fatal, no treatment
Causes:
-sporadic (mutation)
-familial
-transmission (vCJD)
Transmission:
-oral (mad cow disease)
-operative (neuronal tissue)
-blood
Prions are hardy
-high resistance to disinfectants and heat
-hard to remove and/or inactivate
Transmissible forms
Kuru:
-a form of transmissible spongiform encephalopathy TSE
-Identified in a tribe in Papua New Guinea in 1960s
-caused by the ritual of eating the dead (orally transmitted)
-index case hypothetically a tribe member who developed sporadic CJD (mutation)
Mad cow disease (vCJD):
-cows/sheep also get TSEs
-larger outbreak in the UK in 1980s
-caused by feeding cows meat and bonemeal (oral)
-bovine prion can cause disease in humans
-178 people died as a result
-possibly more to come due to long incubation period
Long lasting effect on the Uk:
-health implications
-global ban on British beef exports
Viruses
Are everywhere and infect everything
Not a cell, a shell of protein (capsid) containing nucleic acids, enveloped or non-enveloped, absolutely require a host to replicate
Can be either DNA or RNA, but there are many different types and classifications
11,273 virus species currently known about, estimated to be 1.7 million virus species yet to be identified
Baltimore classification
Developed by David Baltimore
-also credited with the discovery reverse transcriptase
Based on how viruses synthesise their messenger RNA
Shared group characteristics viruses
Same basic viral lifecycle principle
Alternative splicing: increases coding capacity of viral genomes
Genome segmentation (not all): eg viral genes are encoded on separate bits of DNA/RNA, better for evolution
Host range: viruses are found across all 3 branches of life (prokaryotes, eukaryotes and archaea), some are restricted to one host (eg humans), others can jump the species barrier= zoonotic
Viral lifecycle
Large variation due to their genome and other factors- but all viruses follow the same basic principles
1. Attachment to host cell
2. Entry into host cell
3. Release of viral genome from capsid
4. Replication of viral genome
5. Assembly of new virions
6. Egress of new virions from cell
Repeat ad infinitum
Viral effects on host cells
Range from innocuous to lethal
Some viruses integrate into the host genome- HIV
Cell death: due to production of lots of virions
Cell fusion -syncytia
Increased cell proliferation- papillomaviruses
Latent infection= no clinical manifestation until the virus reactivates. Herpesviruses, herpe(creeping in latin)
Group I- dsDNA viruses
Includes herpesviruses, papillomaviruses, polyomaviruses and poxviruses
Varicella Zoster Virus (VZV)
-causes chicken pox upon initial infection
Latency in the neurons surrounding the spine
-dorsal root ganglia
Stresses can cause reactivation, shingles
Some countries vaccinate against VZV
- the Uk doesn’t but you can pay for the vaccine
Group II- ssDNA viruses
Very few infect humans and the ones that do cause no apparent disease
Parvoviruses are likely the most well known- canine parvo can kill young puppies
Torque teno virus is found >90% adults world wide, formally called transfusion-transmitted virus
Accidentally found in the serum of a hepatitis patient
Very little is known about these viruses but there have been more identified across different mammals
Group III- dsRNA viruses
Rotaviruses commonly infect humans
They cause gastrointestinal issues:
-diarrhoea
-vomiting
Can be very serious in babies and young children
Rotavirus vaccine is offered to babies in the UK, 2x doses (1st at 8 weeks and 2nd at 12 weeks)
Group IV- ssRNA (+ve) RNA virus
Lots of +ve sense ssRNA viruses infect humans:
-noroviruses, enteroviruses, flaviviruses, coronaviruses, Astroviruses
Positive sense= genome is mRNA
-Zika virus is a flavivirus that infects humans- transmitted by mosquitos and bodily fluids
Treatment is pain relief, rest and hydration
Epidemic in the Americas in 2010s
Proposed to cause:
-microcephaly in neonates
-neurological disorders (guillain-Barre syndrome)
Group V - ssRNA (-ve) RNA virus
Lots of nasty viruses contained in this group- many have high % fatality rate
-lyssavirus (rabies), influenza, Ebola, marburg, arenaviruses, hantaviruses
Ebola is a member of the filovirus family
Cause= haemorrhage fevers, high mortality rate (up to 90%)
-Zaire strain responsible for most outbreaks- including west Africa in 2013-2016
-broad ranging symptoms: characterised by blood in vomit/stools
-treatment is supportive, promising vaccine candidates
Infection control is key to ending outbreaks
Group VI- ssRNA-RT viruses
Viruses that have a DNA intermediate from RNA- reverse transcription
Human immunodeficiency virus 1= HIV-1
-DNA stage (provirus) integrates into the host genome
HIV-1 is a lifelong infection- progresses to AIDS
AIDS is the failure of the immune system- other opportunistic pathogens can cause disease
Originally jumped from chimps into humans- restricted now due to human adaptation
Between 1981&2009= 30 million deaths attributable to HIV/AIDS
Group VII- dsDNA-RT viruses
DNA viruses but have an RNA intermediate step
-use reverse transcription in virions to make their genomes
Hepatitis B virus is a major problem
95% + adults and older children can clear the acute infection- this drops to 5% in young children where it becomes chronic
~300 million people live with chronic HBV infection
Causes hepatocellular carcinoma
-chronic carriers have a 40% chance of death from HCC due to infection
Important viral pathogens
Influenza A: respiratory infection, zoonotic, lots of types that can recombine (antigenic shift)
Ebola : haemorrhagic fever. Very serious and high % mortality, high consequence of infection. Very few places allowed to work with it
Varicella Zoster: initial= chicken pox, subsequent= shingles. Herpesvirus. Has 2 lifecycles (latent and lytic) can be reactivated
Human papillomavirus 16: typically no clinical disease and cleared but causes cancer. Another DNA virus, major cause of cervical cancer but there is an effective vaccine
Sin nombre virus: heart and respiratory failure, associated with the 4 corners outbreak in USA 1990a. Carried by mice
HIV-1: lifelong infection. No cure. Integrates into human genome
Rotavirus A: gastrointestinal issues. Double stranded RNA virus. Segmented
Bacteria
10^30 bacterial cells on earth
You carry 10x more bacterial cells in your body over your own cells with 100-1000x of different species
A tiny fraction of these have been studied- many are unculturable in the lab
Bacteria found in all environments on earth
Bacteria and humans
Very few microbes are always pathogenic— obligate pathogens
Many microbes can be pathogenic— opportunistic pathogens
Most microbes are never pathogenic— commensals
Not all species are pathogens
Many bacteria can be pathogenic (most never though)
Some are always pathogenic (obligate)- salmonella typhi has no reservoir outside of humans
Some are opportunistic in their pathogenicity
Pseudomonas - will infect most body sites if given a chance
Anaerobes: eg bacteroides fragilis, can infect wounds if they are deep
Bacteria come in different shapes and sizes
Cocci
Bacilli
Budding and appendaged bacteria
Others;
- enlarged rod fusobacterium
-vibrio, comma’s form B dellovibrio
-club rod, helical form
- corkscrew form
-filamentous
-spirochete
Bacterial structure
Prokaryotes:
-lack membrane bound organelles e.g. nucleus
They usually have a cell wall- peptidoglycan
Protruding appendages: flagella, frimbriae
classification of bacteria
Theres many different phyla of bacteria and each has many classes and by definition a lot of individual species
Classification is based on nucleic acid sequences
But there’s also a large division of bacteria into 2 groups - gram negative or gram positive
Bacterial cell wall structures
Gram negative stain PINK:
- they have doubled membranes
-examples include: E.coli, Klebsiella
Gram positive stain PURPLE:
- they have single membranes
-examples include: staphylococci e.g MRSA, streptococci
How do bacteria cause disease
Varies loads
Some bacteria invade cells (intracellular)- salmonella
The pathology of disease depends upon:
-bacterial activity
-toxin production, direct tissue damage
-host response
-immune system
Bacterial toxins
Exotoxins- proteins secreted by bacteria
Synthesised for a number of reasons
-destroy host cells
-release cellular contents
- allow invasion
Clostridium botulinum:
-food poisoning
-lethal neurotoxin that causes paralysis
Also the stuff used in Botox
Symptoms:
-facial nerve paralysis
-dry mouth and throat
-nausea and vomiting
-abdominal distension
-problem of urinating
-double vision
-slurred speech
-tachycardia
-muscle weakness
Lipopolysaccharide LPS
An endotoxin - found on gram negative bacteria
Major immune stimulator- causes sepsis
Only lipid A is toxic- major immune response
There are many types possible- specificity caused by terminal repeat regions, salmonella >1000 types of LPS
Flagella
Molecular motors used to swim
Important in pathogenesis
Often v. Immunogenic and cause inflammation
Chemotaxis- can move bacteria towards or away from chemical attractants/repellants
Fimbrae (pili)
Shorter and finer than flagella
Several different functions:
-attachment to host cells (UTIs)
-host cell invasion
-roles in conjugation
Conjugation= transfer of plasmid DNA, this can drive AMR
Important bacterial pathogens
Escherichia coli: bacteraemia, UTI, GI. Gm- often part flora
Staphylococcus species: wound infection, bacteraemia. Gm+ often part of flora, MRSA
Mycobacterium tuberculosis: tuberculosis Lung, 1/3 world carry
Pseudomonas species: varied disease, Gm- environmental
Streptococcus pneumoniae: RTI, Gm+ aerosol
Campylobacter species: GI, Gm- 1 cause food poisoning
Clostridium difficile: hospital acquired infections, sporulates overgrowth after antibiotic use
Neisseria gonorrhoeae, N.meningitidis: gonorrhoea, meningitis, species specific tropism
Antibiotic resistance AMR
AMR is a major global threat to everyone
Routine surgery will become deadly due to infection
1.2 million deaths were attributable to AMR in 2019
New drugs hard to get approved - numbers declining over time
Bacteria can become resistant fast: faster than the discovery rate, misuse is another reason for resistance
The UN predicts up to 10 million deaths annually- as a direct result of AMR
Fungi
Can be single cell or multicellular
They are eukaryotic, similar to human cells
Because of this it makes them harder to treat
They have a cell wall that contains chitin
Very few have been studied thought to be up to 1.5 million species
Includes lots of useful things:
-yeast
-moulds
-mushrooms
