First microscope developer is unknown
There a few people in making us aware of the microscopic world (17th century)
- Robert hooke
- Antonie van leeuwenhoek

Robert hooke publishes Micrographia in 1665

Came up with the term “cell” (room in latin)
Originally thought cells was just in plants

Antonie van leeuwenhoek sees animalcules

Then rights lots of letters to Royal Society of London
- educated , scientific body
Was not taken seriously by the scientific body
- First describes bacteria as (oral)

Spontaneous generation (17 and 18 century)

Widely accepted

People believed things just spawned from nonliving things
- “Maggots came from rotting meat”
Took nearly 150 years to settle the debate

Francesco redi’s experiments

1668, uncovered, covered (cork), and gauze (air was allowed to come in) covered met left to rot
- Air back then = vital force
Results: only the uncovered meat had maggots

John Needham

1748
Maybe only animalcules could spontaneously generate
- Boiled gravy 1 hour, transferred to flask sealed with cork
- Flasks then became cloudy

Suspections: what if the flask, cork, air, etc. wasn’t sterile

Spallanzani (doesn’t accept needham’s experiment and redoes it 1767

Heated broths, sealed tubes by melting glass top
Results: no growth
- Suspections: no vital force so of course nothing grew

As of 1767, no one could figure it out until 100 years later

A cash prize was sent out to find out the answer
- This is where Pasteur comes in

Pasteur

Made swan neck bottles full of media and boiled them
Lets them boil and after 7 days he tips a little near the opening and then sits it upright again and sees for growth
- there is growth after, signifying the end of spontaneous generation

Three scenarios

Never tipped it
Tipped it
Broke the top off

Pasteur showed that microbes ferment sugar
- Proposes pasteurization
  - Controls microbial growth
France enlisted Pasteur and wanted to figure out how wine gets fermented and how to make it never go bad
- Found yeast in good wine and bacteria in bad wine

Pasteurization - Heat the grapes to kill everything, then add in the good yeast and microbes to make the wine good

Then proposes the Germ Theory 1860s
- Germs can cause infectious diseases
  - Led to “paradigm shift”
Develops the rabies vaccine
He also switches from Ochem to disease prevention

Germ Theory

Robert Koch builds on Pasteur’s germ theory by developing a method for showing causality
- Publishes Koch’s postulates (1875)
- Specific microbe causes a specific disease
Key: being able to separate organisms from each other and grow in the lab

Found anthrax bacili in dead animals and had to separate it from other bacterium
- Postulate sequence
  - First: Thought of using a petri dish and could separate it in their
  - Second: Then made a pure culture of the anthrax
  - Third: Used that pure culture and inject it into a subject
  - Fourth: HAVE to get the same culture bacteria from the subject’s death
Possible weaknesses of the postulates:
- Unknown if the animal was already dying from something else
- Not everything grows in a lab
- Some bacteria need specific conditions
- What if the disease only affects humans

After Koch’s postulates were formed, people were most likely terrified.

Bary Marshall believed in 1981 that ulcers were not stress induced rather an infectious disease

Clinical staff that obtained biopsy samples from ulcer patients developed antibodies against helicobacter. However, the family household members of patients with ulcers did not develop antibodies against Helicobacter.
He then swallows it and gives himself ulcer’s to finish Koch’s fourth postulate and finish the (cause and effect) process

Three themes

sumthin else i forgot

Germ theory

Koch’s postulates

What is the difference between prevention and treatment (historically)

1847

Before the germ theory, semmelweis advocates hand-washing with chlorine for those delivering babies to prevent childbed fever
- This is because 90% of mother’s were dying after birth
- Resulted in a decrease in percentage
No conceptuality of why hand washing worked

1865

Joseph lister uses disinfectant (phenol) to prevent spread of infections
Florence Nightingale introduces antiseptic techniques to nursing

1920

Alice catherine evans showed that bacteria taht caused disease brucellosis could be transmitted through cows milk
- Advocated for pasteurization of dairy product in US (1930)

Prevention

1798 Jenner’s cowpox vaccine prevented people from getting human smallpox
Pasteur works on chicken cholera and rabies vaccine
- Rabies is a post-exposure vaccine
- Pasteur dedicates the rest of his life to immunization
Make people smell or touch smallpox scabs so they get an acute portino of it and to build immunity to it
Cowpox can be given to humans as a vaccine for smallpox

1885

for our bodies were bit by a suspected rabid dog in Newark, NJ
Some dude really liked Pasteur and was like i would boat over to paris just for that vaccine just to show the world that people are smart and shi

Chemotherapy

Question was raised, can germs be killed inside a person
Treatment of disease using chemical substance
Paul ehrlich
- Coined the term “magic bullet”
- This is selective toxicity
- Salvarsan 606 treatment for syphilis succeeded
  - 1910
- Ehrlich wanted a drug that could kill any disease
- Salvarsan had some arsenic
Gerhard Domagk
- Prontosil (sulfa drug precursor), an antibacterial drug that got activated inside the body
  - Wouldn’t kill stuff in the lab
  - Got the Nobel Prize in 1939

Antibiotics - Chemotherapeutics made by other living things

Penicillin made by fungus

Alexander Fleming plate got his plate contaminated but the bacteria wasnt growing in the areas with mold
People did not know how to grow mold properly to treat everyone with it
- Nobel prize, 1945

Cell Anatomy

Prokaryotes and eukaryotes

Bacteria and archaea have similar ribosomal structures, the sequence of ribosomal RNA gene (rRNA 165) are not similar

Eukaryotes have different ribosomal structure from prokaryotes
Prokaryotes were thought to be the first living things
Photosynthetic prokaryotes then most likely released oxygen
3.8 billion years ago prokaryotes most thought to first be

The concept of species is not well-defined for bacteria and archaea and is problematic

This is problematic mainly because Horizontal gene transfer occurs among bacteria which lead to more variation within species

Prokaryotic cell shapes and arrangements

This is one of the Central ways of describing and organizing prokaryotes
- Cocci, paired and 1micrometer
- Bacillus bacilli little tic tac shape, 2 micrometer
- spirillum/spirilla spiral squiggly shape and 5 micrometers
- Comma shaped one, vibrio
- More corkscrew looking one, spirochete
Majority of prokaryotes are monomorphic
- Come in one shape
- Mainly to the cell wall
Some are pleomorphic
- Differently shaped but same species

Some species of prokaryotes stay connected to each other after cell division

Binary fission

For a coccus (ball) there are

Single
Diplo
Strep (chain)
Staph (cluster)

Bacillus shaped (tictac)

Since

Diplo

Strep

Palisades (lined up side by side not end by end)

All prokaryoes have a

plasma membrane
Ribosome
Cytoplasm
DNA (nucleoid)

Flagella

Structure for movement
- Run (counterclockwise)
- Tumble (clockwise)
Rotates for prokaryotes
Advantage is basic movement to go where is important and necessary
Taxis
- Term for how something in the body knows to go somewhere (stimulus)
- Trail of chemicals or something like light to show where to go
- chemo/photo taxis
This is how the prokaryotes know where to go

Attachment structures

Fimbriae
Pili
- Attachment to another cell for DNA exchange

Domains with prokaryotic cells

Bacteria and archaea

Domains with eukaryotic cells

Eukaryotes

Kingdoms for euk

Animalia

Plantae

Fungi

Fimbriae for attachment

Glycocalyx

Sugar coat
Made of usually polypeptides and polysaccharides
Common kinds
- Capsule
- Slimelayer
Functions:
- Protects against dehydration
- Source of nutrition when energy stores low
- Attachment to surfaces

Slime layer

Coat loosely attached to outside of cell
Allows for attachment to surfaces and biotin

Capsule

Coat firmly attached to outside of cell
Needs a negative staining
Contributes to bacterial virulence
- Protects the cell from phagocytosis (immune system mechanism)

Virulence factor - something that makes the microbe more pathogenic

Cell envelope - outside of plasma membrane

Protects cell from changes in external environment
Just means cell wall + cell membrane

Almost all prokaryotes have cell walls

All cells tend to have negative charges

Bacteria and eukaryotes have lipid bilayer

Archaea have lipid monolayer

Things small and nonpolar can move through cell membrane blabh lbhal blha blah

Water channels: aquaporins

Water moves from LOW → high solute concentration

Cell wall protects from a hypotonic environment (more solutes inside cell)

Water wants to go in, cell wall stops the cell from bursting

Having a cell wall = buff

Bacterial cell wall components

Peptidoglycan
- Found in all bacterial cell walls
Lipopolysaccharide
- Found in gram negative cell walls
Mycolic acids
- Found in mycobacterium and Nocardia species ONLY
- Acid fast bacteria

Peptidoglycan

Series of sugars
NAG-NAM alternating sugars
Multiple strands that are connected together by peptides
Will hold the cell membrane together like a lattice holding a pie top
Can be thick or thin

Penicillin stops this from forming, no wall form = water can now burst the cell

Lysozyme in tears, saliva, and sweat enzymatically breaks down peptidoglycan

Lipopolysaccharide (LPS)

Only for gram negative bacteria

Have long sugar strands with a lipid on the outside
- acts as a second outer membrane
Immune response to lipid A and O polysaccharide (these are in the lipopolysaccharide)
Immune response also to flagella

endotoxin = Lipopolysaccharide

White blood cells respond to large amounts of free LPS in the blood or gut
White blood cells then release cytokine (immune system proteins)
- This however also damages the body
- This is how sepsis symptoms appear (fever and septic shock)

Gram positive and gram negative

Gram positives have a very thick peptidoglycan layer with teichoic acids attached to it to anchor it to the membrane

Gram negatives have LPS attached to an outer lipid bilayer external to a thin peptidoglycan layer.

Porins are embedded help move things into the cell

Gram +/- based on dude named Gram who wanted to find a stain that only stained all bacteria instead discovered that:

gram- bacteria stains pink

Gram+ stains purple

Flagella for gram +/-

Flagella protein in prokaryotes in flagellin

In gram+, there is only 2 rings to anchor the flagella

In gram -, there are 4 rings because there are two membranes (3 layers)

Spirochetes

All gram negative
Do not have flagella coming off the end, instead the flagella is embedded on the cell

Syphilis

Can go through the skin because its spirochete movement

Mycolic Acid

Long waxy lipid chains exterior to peptidoglycans
Takes a long time to make
Takes months to grow
Drugs for TB targets the mycolic acids to break down the cell wall
Acid-fast staining
- Specific stain for mycolic acids

Acid-fast stain and gram stains hard to differentiate

Archaea cell walls

No peptidoglycan
Commonly has an s-layer

Internal structures

Ribosomes

Prokaryotic: 70S

euakryotic : 80S

Inclusions

May be made of polyphosphate, Glycogen, Sulfur or other molecules

Biggest releasers of endospores

Clostridium, Bacillus

Endospores can last through

High heat
Lack of water
Radiation
Exposure to toxic chemicals

Bacteria form endospores when deprived of some key nutrients
- This is mediated through quorum sensing
  - How the bacteria communicate to know when to make endospores
Endospores are metabolically inactive
- Endospores are like their last attempt to survive

Endosymbiote have to live within a host

Lynn Margulis

Endosymbiotic theory
- Believed prokaryotic cells joined to live symbiotically and ended up changing into eukaryotes
- This theory accounts for the nucleus, mitochondria, and chloroplast
- Microbe structure entered the cell and the cell became dependent on it
Idea that the nucleus cam from the plasma membrane

Termites rely on the protozoa and gut inhabitants in them to break down the wood they consume

Endosymbiotic theory

Chloroplasts and mitochondria are degenerate bacteria that earlier in history merged in another cell

Evidence for this:

Based on similarities between bacteria and mitochondria/chloroplasts
Endosymbionts already exist innature

Prokaryotes usually only have one circular chromosome

Binary fission
- Asexual
- Two identical cells
- Much faster and easier process compared to mitosis/meiosis

Eukaryotes are

Animalia
Plantae
Fungi
Protists

Differences between prokaryotes and eukaryotes

Eukaryotes have a organized complete endomembrane system

In eukaryotic cells are membrane bound organelles

Nucleus, Mitochondria, etc
Stuff that is surrounded by a membrane

Eukaryotic movement

Flagella
- Structurally different from prokaryotes flagella
- Wrapped in a membrane
- Made out of microtubules
- Movement is wavelike instead of spinning
Cillia
- Similar euk flagella structure, but shorter
- Commonly in large numbers covering the outside of the cell
- Usually moves in one direction
- Movement is oar-like (power stroke)
Amoeboid
- Pushing and retracting of the plasma membrane through cytoskeleton components
- Morphs the membrane to thrust it forward like a foot pushing off

eukaryotic cell wall components

Plants
- All have cell wall
- Made from cellulose
Fungi
- All have cell walls
- Made from chitin and/or cellulose (others too)
Protists
- Some have cell walls
- Calcium carbonate
  - Makes limestone
- Silica
- Other proteins and carbohydrates

Microbial Growth

Most bacteria reproduce from binary fission

Reproductive potential of E. coli
- About 20 minutes in ideal conditions

Dna is replicated
Cell wall and plasma membrane begin to split
A cross wall forms completely around each DNA
Cells separate

Time it takes for the population to double

Generation time

Bacterial Growth Curve (closed batch)

Lag phase
1. Cells adjusting to new environment
2. No significant increase in growth
Log phase
1. Great Increase in numbers
Stationary phase
1. All nutrients are used up and the rate of growth and death are the same
  1. Cells are still dividing here!!!!
Decline phase
1. Binary fission might still be happening but the rate of death is faster than growth

Log scale = y axis is increasing in factors of tenfold

10, 100, 1000, 10000

With pathogens, the body has an essential infinite nutrient source so there isn’t a stationary phase

This is why the immune exists because without it, the pathogen gets worse and worse

Generation time can be determined by the growth curve

This is from picking a point in the log phase and seeing how long it took to get there

When cells make endospores they die before releasing them

Sporogenesis

Same start of binary fission
The DNA is given a super strong outer layer
The other half of the cell after getting split off dies and the endospore exists until potentially becoming a vegetative cell (active cell)
No net increase in population

Physical and chemical factors that affect microbial growth