PATH 3700

Evolutionary Fitness + Mutilations

How EF works

  1. Mutation creates variation

  2. Favorable mutation will continue & unfavorable will be selected against for continuing

  3. Reproduction + Mutation happen

  4. But this time more are less likely to survive and the one most fit will reproduce again

  5. More reproduction


Ex: Charles Darwin Finch beaks

  • Natural selection may be a + or - dependent on circumstance


Virulence

1st Definition: The invasive Power of a Microorganism

Best definition: The capacity of a microbe to produce disease

  • Or the Properties of a pathogen that allow them to produce disease

  • My ways is “how severe the disease is caused by a pathogen”

Level of Virulence

  • Ebola +HIV has highest virulence while normal flora like bacteria are the weakest

  • Quantitation of virulence

    • LD 50= Lethal dose for 50%kill

    • ID50 = infectious dose for 50%

  • “Virulence is a relative Property” means that we determine / categorize how virulent a pathogen is by comparing the severity (how bad) of the diseases it causes under specific conditions.

  • Host can affect the strength of a disease


Fitness vs Virulence

  • The goal of Pathogen / disease is to make more of itself (multiply) not to kill = maximize transability

  • Problem: If too much pathogen within a host ?

    • Pathogen overwhelms host and host dies

    • Pathogen does not want that


Replication Rate. Virulence, and Transmitability

  • Total transmission + virulence = quadratic (has a limit bf bad)

  • Total Transmission + Replication = quadratice (has a limit bf bad)

  • Virulence + Replication = linear (no limit as replication increases)


Rapid Evolution

  • RNA viruses have a lot of mutations + genomes because they are an independent Rna polymerase but not good at reproducing with high fidelity (will induce)

  • Bacteria genome is small, but mutation rate is very high bc dont have a lot of DNA repair enzyme to prevent mutation

  • Mycoplasma as highest # of mutations


Gene Duplication

1) Duplication = Pathogen DNA can make an extra copy of gene

2) Divergence = over time 2 copies can accumulate dif mutations

  • Sub functionalization = 2 gene copies spilt and divide work

  • Neofunctionalization = one copy gene gets a new function (most useful mutation)

  • Degeneration / Gene Loss = one copy gets a mutation then looses function


Mycoplasma Galliscepticum

Jumping Hosts

  • Atypical bacteria - reductive evolution, no cell wall, obligate parasite, smallest living thing

  • VLHA = series of genes (not independent)

    • We don’t know function but can have a huge diversity in mutation of vlha strains

How it relates to fitness

  • mutation jump from chicken to finch birds

  • Divergent mutation can occur = Different molecular mechanism for transmition = controls virulence

    • Reason could because of mutation in other hosts

Viral Quasi species

  • RNA virus just within a cell polymerase cannot replicate genome every copy might have an different mutation that may be good or worse at replicating genome

  • consensus sequence = maintain certain genomes that are wanted

  • Fitness will go down as Extensive replication, quasi species and replication of bottle necks go down

  • More diversity / variants of virus is good as more likely to survive

In summary: Quasi Species is a group of closeley related but small different version of the pathogen that exists in the same host (so a diverse mutation cloud)


Quasi species: Antibody Escape Varients

  • If antibodies have a low affinity it will not stick as strong and will fall of the epitope + if antibodies fall of they are not effective + virus will outcompete host. So host must go thru multiple mutation

  • Down side is that epitome will fit more / broaden but become less specific and unique as mutations occur.


Foot and mouth Disease Virus

  • Picorna virus

  • Genome: SS+ RNA virus

  • Envelope: Non enveloped, no spike proteins

  • Effect pigs + cows, etc

    • Bad for farming bc animal cannot eat as in distress

    • Food production goes down

    • Eradicated in US but was the most transmissible ever

  • Vaccine History:

    • Quasi species occurred so vaccine variant from wild animals did not work


Antigenic drift + Shift in inflenza

  • Antigenic drift = is when small changes can gradually make antibodies from previous infections or make vaccines less affective

    • Ex: Seasonal Flu changes (inf a+b)

  • Antigenic Shift = is when big sudden genetic changes happen and alters the gene and potentially makes a different virus which can cause an pandemic

    • Video: Same cell gets infected w/ 2 different strains human and high pathogenic epidemic strain.

      • cause potential pandemic (inf a)

      • pigs is a mixers and can contact a type of avian flu that can potentially pass to humans.


Transmissibility vs High Mortality

  • Why is it that humans are so effected by avian flu

  • Alpha 2,6 salic acid (humans)→ U-Respiratory: Low mortality, easy transmission

  • Humans and birds produce Alpha2,3 salic acid in the alveoli its hard to get but has high mortality → L-Respiratory

    • 1918 Spanish flu - from American pigs

    • (discussible form why there where more ppl dying on Spanish flu than covid)

  • SARS - CoV2 covid 19

    • Biggest mortality since Spanish, biggest economic impact


Mutations + Making Covid-19 more transmissible

  • D614G variant replaced original Wuhan strain

    • Started jan 2020

    • Global strain June 2020 w/ increase transmissibility

  • B.1.17 variant start sept 2020 + more transmissible

    • Global in December

    • H69

    • N510 mutation binf to RBD w/ ACE2 better affinity



FTransmission + Emergence

Most Common Routs of Entry for Pathogens

  • Mucosal Surfaces (by far most common)

    • Respiratory tract lining, intestines, stomachs (all considered the outside of the body to microorganism)

    • Tissue = inner body

  • Conjunctiva = eye, near sinus

    • Rub your eyes + will be flushed by tears

  • Genital / anus


Modes of Infection / disease Transmission

  • General Transmission (not human to human or animal to animal)

    • Wind, water, spore inhalation, entry into skin

    • Animal + vectors = mosquitos, fleas, birds etc.

  • Human to Human Transmission

    • Direct Contact = touching others (HIV, Herpes, Ebola)

    • Indirect Contract = Touching surfaces like handles or air (influenze, noro)

    • Droplets = Don’t survive long, sneeze or open mouth (Ebola, bord)

    • Airborne = pathogen aerosolized and stay ineffective (influenzas, tuber)

    • Fecal - oral = Contaminated water or food (cholera, Noro, shagella)

      • Grow in GI tract


Viral Survival on surfaces (fomites/nonliving things: ex covid)

  • Copper = 4hrs

  • Cardboard = 24hrs

  • Plastic 2-3 days

  • Stainles steel 2-3 days

    • all if not in sun


Respiratory Particle size from Cough / sneeze

  • Aerosols can be more dangerous in spread if air circulation for distance


Infectious dose

  • # of particles of a pathogen you come in contact w/

  • Different for every pathogen some don’t need a huge host + also depends on immunity of host.

  • Also route of entry may differ.

  • Coughs + sneezes cause most droplets

  • exercising

Masks

  • Cloth - depends on material

  • Surgical - loosely fit

  • N95 - most correct but not environmentally friendly

  • Protect Host and those outside


Latent Period Vs pathogenic shed

  • Incubation period = host been infected but bf feeling sick (initially should be only shedding virus when feeling sick but certain disease can shed before)

    • Latent period = partially developing but

    • Covid-19 = can be shed during incubation

  • Period of communicability = when you start shedding the disease + feeling sick. (Sometimes better than others)

    • After getting better you still can shed the disease

    • earliest spread most likely to infect most


BRV or Ro

  • Ro = the average amount of people that will get infected by another infected person (population statistic)

    • ex Ro = 1.5 = infect 1 - 2 ppl

      •  Ro = 2 = infect 2 ppl

      • Ro = 1 = infect 1 per (sustainable)

      • Ro = 0.7 = infect 0 ppl (mers dont really spread)

      • Ro = 17?? =

    • Measles spreads the most

    • Mers spreads the least if not at all

  • Ro is circumstance Dependent

MOST IMPORTANT POINT OF A DISEASE

1) Ability to spread (all it wants to be is transmissable)

2) Severity if Disease


Super spreaders

  • Depends on the host ability to spread

  • ex: Typhoid Mary

    • salmonella disease (fecal oral) → gallbladder / Gi tract

    • Never washed her hands but cooked for ppl

    • she was asymptomatic in comparison to those she spread it too

    • Jobs

    • Events

    • Herd Immunity = v

      • If only a few ppl is vaccinated, spreading won’t diminish

      • If most are, spreading will diminish


Vaccination + herd Immunity

  • Vaccination if most are makes sure transition to occur

  • The more transmissible the virus is the more herd immunity you need in order to stop transmission in herd.


Zoonotic Disease

  • Transmitted Between humans + animals

    • Most pathogens in humans are zoonotic

    • from wildlife or domestic animals


MERS

  • Beta-Coronavirus (2012)

    • bat origin → camels (intermediate host)

    • Not from human to human but from camels to human

    • High Virulent (35% mortality, covid = 1% mortality)

    • Mers S-Korea 2015

      • Eradicated by quarantining for 3 months


Reservoir, Intermediate, dead End Host


  • Reservoir Host = Co-evolved w/ virus + only the strong survive, weak killed off

    • Part of normal flora of Host

    • exhibit very little pathology

  • Intermediate host = just a host, can show signs

    • Virulence High ( like pigs)

  • Dead end host = virus ending w/ host, humans


Intermediate Host of Beta Coronaviruses

  • Reservoir host = Bats

  • Intermediate host = Camels (Mers) / cats (Sars) / covid 19 (pangolins)

  • Dead end host = Humans


West Nile

  • Revisor host = American crows

  • Intermediate host = dengue / mosquitos

  • Dead end host = humans


Quarantine, Isolation, social Distancing

  • Quarantine = someone exposed but not exhibiting symptoms stay quarantined until incubation period is over. (home)

  • Isolation = someone has symptoms and stays in isolation until symptoms Arnt apparent v/ no longer shedding. (Hospital)

  • Social Distancing = stay away from ppl as much as possible in order to reduce transmission


intervention and effect on Ro: Flattening the curve

  • W/ out protective measures increases the amount of protective measures





Microbial Pathogens

Categories of Pathogens

  • Bacteria = single celled organisms w/ out nucleus

    • Prokaryote

  • Virus = can’t live on its own requires a host living cells to survive, borderline living

  • Fungi = single organism

    • Eukaryote (biggest pathogen)

  • Protozoa = single cell organism w/ nucleus

    • Eukaryote (biggest pathogen)


Human pathogens

  • Viruses are most prevalent pathogen


Prokaryote vs Eukaryote

  • Prokaryotic cell = No nucleus

    • no organelles

    • DNA in nucleoid / cytoplasm

  • Eukaryotic cell = Has nucleus

    • (A) Sexual reproduction

    • Has organelles that contain DNA


Shapes of Bacteria

  • Cocci - circle shaped bacteria

  • Bacilli - rod shaped bacteria, some come w/ flagella, spore formers (inactive form)

  • Others


Gram - and gram +

  • Gram (+) = cell wall on outside

    • Thick cell wall

    • stains blue/purple

    • Needs assistance for toxic shock

  • Gram (-) = cell wall inside 2 cell membranes

    • Thin wall / easy to break wall

    • Stains pink / red

    • Can cause toxic shock by itself

    • More resistant


Viral Structure

  • Genome = DNA or RNA / ss or ds

  • Capsid = made of protein that protect genome

    • Some viruses have spike proteins

  • shapes =

    • Helical = any shape but not icosahedral

    • Icosahedral = soccer ball shape

  • Enveloped or not = if they wrap themselves in cell membrane of host or not


Viral Replication

1) Spikes used for cell receptors and entry of virus

2) virus fuses with host cell, viral genome into host cell

  •    Envelope allows for easier transmission

    • Envelope disguise virus

3) more copies + more capsid proteins are made, good genome

4) Budding: viruses force way out of cell wrapping themselves with host membrane


3 ways a virus can exit a cell

  • Lysis = virus destroys / ruptures host cells to release new virus particles

  • Exocytosis = virus go thru ER and Golgi (non-envelope + most gentle)

  • Budding = comes out wrapped in host membrane


Pox’s = biggest


Fungi yeast vs mold

  • Fungi reproduction

    • Can reproduce asexually (mitosis)

    • spores = metabolically inactive part of the cell

      • Form rigged cell wall


Protozoan Pathogens

  • Eukaryotes





Out break occurs

Endemic = Diseases that are around all the time

  • Cases are constant

Epidemic = Newley emergence

  • # of cases increase

Pandemic = epidemic spreads around the world

  • Global epidemic