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metabolism
-Collection of controlled biochemical reactions that take place within a microbe
-Ultimate function is to reproduce the organism
-Anabolism and catabolism
anabolism
-Building/putting together
-Requires energy (endergonic)
-Ex: building macromolecules and cellular structures
catabolism
-Breaking apart
-Releases energy (exergonic)
-Ex: breaking down food and macromolecules
enzymes
-Proteins that speed up chemical reactions by lowering the activation energy, or the amount of energy need to start a chemical reaction
-Specific for one type of substrate
-High temperatures and low pH will lead to denaturation and loss of shape, rendering these functionless
ATP and ADP cycle
ATP --> breakdown of ATP to release energy to fuel endergonic reactions --> Phosphate released and ADP remains --> ADP takes in energy and combines with another Phosphate for synthesis of ATP --> ATP formed again
oxidation-reduction reaction
-LEOGER (Losing Electrons is Oxidized, Gaining Electrons is Reduced) or OIL RIG (Oxidized Is Losing, Reduced Is Gaining)
-Molecule that gives up electrons is oxidized and is the reducing agent
-Molecule that accepts electrons is reduced and is the oxidizing agent
NAD+/NADH
-Coenzyme that serves as an electron carrier
-Holds onto electrons and H+ until they are needed in the ETC
Carbohydrate catabolism
-Many organisms oxidize carbohydrates as their primary energy source
-Ie. oxidation of glucose
aerobic vs. anaerobic
-O2 is the final electron acceptor in aerobic respiration while O2 is NOT the final electron acceptor in anaerobic respiration
-Both processes consist of glycolysis, the Krebs cycle, and the ETC
fermentation
-Process by which glucose is broken down into ATP and lactic acid
-Essentially glycolysis on repeat
-Produces much less ATP than cellular respiration
chemical formula for cellular respiration
C6H12O6 + 6O2 --> 6CO2 + 6H2O + ATP
eukaryote respiration
-Glycolysis occurs in the cytoplasm
-The Krebs cycle and ETC occur in the mitochondria
prokaryote respiration
-Glycolysis and the Krebs cycle occur in the cytoplasm
-The ETC occurs in the cytoplasmic membrane
Glycolysis
-In --> 1 glucose
-Out --> 2 pyruvate, 2 ATP, and 2 NADH
-The only anaerobic stage of respiration
Intermediate stage
-In (per 2 turns) --> 2 pyruvate
-Out (per 2 turns) --> 2 acetyl CoA, 2 NADH, and 2 CO2 (breathed out)
-Occurs within the mitochondrial matrix in between glycolysis and the Krebs cycle
-Has 2 turns
Krebs cycle
-In (per 2 turns) --> 2 acetyl CoA
-Out (per 2 turns) --> 2 ATP, 6 NADH, 2 FADH2, and 4 CO2 (breathed out)
-Occurs in the mitochondrial matrix and has 2 turns
-After this step of cellular respiration, all of the electrons and H+ are on the electron carriers (NADH and FADH2) and all 6 Carbons have been breathed out as CO2
FADH2
coenzyme that serves as an electron carrier during cellular respiration along with NADH
30-38 ATP
net ATP after cellular respiration
Electron Transport Chain (ETC)
-In --> 10 NADH and 2 FADH2
-Out --> 26-34 ATP and 6 H2O
-Final step of cellular respiration in which the electron carriers drop off the electrons and H+, and an electrochemical gradient is created by movement of H+ ions out of the membrane
-Steps:
1.) NADH and FADH2 drop off electrons and H+
2.) The electrons are shuttled across the membrane by carrier proteins as H+ is pumped outside of the membrane, creating a H+ gradient in which there is a higher concentration of H+ on the outside of the membrane than there is on the inside
3.) Because a H+ gradient was created, the H+ want to diffuse from higher concentration to lower concentration. At the end, ATP synthase opens up and allows H+ to flow through, using the energy provided to convert ADP and phosphate to ATP.
4.) Electrons are accepted by O2, which combines with the H+ that returned via ATP synthase to form H2O.
cyanide
-A poison that prevents the movement of electrons across the ETC
-Inhibition of electron movement --> H+ does not get pumped out across the membrane --> no H+ gradient is created --> ATP synthase does not open --> ADP and phosphate are not converted to ATP --> no energy for cells to continue performing normal functions --> cell death
characteristics of viruses
-NOT a cell
-Cannot perform metabolic pathways
-Cannot reproduce on their own (the host cell does the replicating)
-No cell parts
-EXTREMELY small
genome and capsid
at minimum, a virus must have these two parts
virus genome
-Contains the instructions to build more viruses
-Either DNA or RNA, never both
capsid
protein covering of a virus
virus envelope
-Structure made of phospholipids that surrounds the capsid in some viruses
-May or may not be covered in spike proteins (ie. COVID-19)
+ssRNA
single stranded RNA that moves directly to translation (ie. polio virus)
-ssRNA
single stranded RNA that is used to make more +ssRNA (ie. influenza)
retrovirus
a type of RNA virus that transcribes RNA into DNA
virus replication process
1.) Adsorption
2.) Penetration (and uncoating if necessary)
3.) Biosynthesis
4.) Assembly
5.) Release
Adsorption
-Attachment of a virus to receptor sites on a host cell
-Mediated by the matching up of proteins on the surface of the virus with proteins on the host's cell membrane
-Antibodies block attachment
influenza adsorption
hemaglutinin and neuraminidase proteins on the surface of the virus attach to sialic acid glycoprotein of respiratory tract cells
COVID-19 adsorption
spike proteins on the virus envelope attach to ACE2 proteins on the surface of the cell
virus
-Cell hijackers that turn cells into virus factories
-There are ones to infect every kind of cell (they are specific like enzymes and substrates)
tissue tropism
what type of cells within the host that a virus can affect (ie. proteins and receptors)
host range
what organisms a virus can infect
HIV
virus that binds to CD4 helper T cells found only in humans
Rabies
virus that can infect humans and many other kinds of animals
Penetration
-A virus enters the host cell via direct entry, membrane fusion, or endocytosis
-With direct, the virus genome is dumped directly into the cytoplasm
-With membrane fusion, the virus and cell membrane of the host fuse, and the capsid is released into the cytoplasm
-With endocytosis, the virus is engulfed by a vesicle and released into the cytoplasm
uncoating
the capsid is removed and the virus genome is freed into the cytoplasm
biosynthesis
-Process by which a virus hijacks the host cell's machinery to create more virus parts
-Transcription and translation occur to create more capsids, spike proteins, etc.
-DNA replication occurs to create more virus genomes
assembly
the newly created virus parts are assembled into a complete virus
release
newly created viruses are released from the host cell either via lysis or budding off from the cell membrane (part of the cell's membrane becomes the virus envelope during budding)
consequences of virus infection
-Death of the host cell and release of the virus via lysis
-Transformation --> virus changes normal cells into cancer cells (ie. Hepatitis, HPV)
-Persistent infection --> slow release of the virus without cell death (often seen when viruses are released via budding from the cell membrane)
-Latent infection --> the virus is present but is not replicating, and stress/hormonal changes may trigger it to become a lytic infection (ie. Herpes, chickenpox, shingles)
-Cell fusion --> an example of this is how measles causes brain cells to fuse together, leading to loss of cognitive function
bacteriophage
-A type of virus that infects bacteria
-Parasitize a specific bacteria
-Most contain dsDNA but some RNA types exist as well
-Can often make infected bacteria more pathogenic
-Lytic or lysogenic infection
lytic infection
adsorption --> penetration (and uncoating) --> biosynthesis --> assembly --> LYSIS OF CELL
lysogenic infection
-A phage integrates its genome into the bacterial chromosome, so when the host cell divides, the phage's DNA is passed onto daughter cells
-Can sometimes be converted back to a lytic infection under stressful conditions
-Lysogenic conversion (gives the bacterial cell new genes)
-Adsorption and penetration, but no biosynthesis or assembly and NO LYSIS
lysogenic conversion
-A bacteriophage changes the behavior of a bacteria during lysogeny
-Often is the conversion of bacteria from being nonpathogenic to pathogenic or just simply makes a pathogenic bacteria even more pathogenic than it was
-Often involves acquisition of a toxin since many bacteriophages encode for a toxin (ie. diptheria toxin or cholera toxin, which causes super watery diarrhea)
bacteriophage therapy
therapeutic use of bacteriophages to target and kill specific bacterial infections (especially in instances where the bacteria is antibiotic resistant)
virulent phage
bacteriophage that reproduces only by a lytic cycle
temperate phage
bacteriophage that can be either lytic or lysogenic
COVID-19
virus that uses its own enzyme called replicase (RNA dependent RNA polymerase) to make more RNA from its RNA genome
varicella zoster
-Virus that causes chickenpox and shingles
-Can remain in a chronic latent state by hiding from the immune system within nerve cells
Kirby Bauer test
-Determines susceptibility or resistance of a bacteria to an antibiotic by measuring the zone of inhibition
-Process: swab bacteria with a cotton swab and spread it over the entire agar plate --> put antibiotic paper disc on the agar --> incubate --> the next day, measure in mm. the diameter of the area that the bacteria does not grow around the disc --> compare to a susceptibility chart
zone of inhibition
-Area in which no bacterial growth is present on an agar plate after using the Kirby Bauer method
-Measured in mm.
antibiotic resistance
-An adaptive response in which microorganisms begin to tolerate an amount of drug that would normally be inhibitory
-The microbe grows in the presence of the antibiotic
-Can either be intrinsic or acquired
antibiotic susceptibility
the microbe's growth is inhibited in the presence of the antibiotic
Klebsiella pneumoniae carbapenemase (KPC)
-Bacteria that lives in GI tract
-Klebsiella pneumoniae is part of the body's normal flora
-Carbapenemase is an enzyme that breaks up carbapenem antibiotics, causing klebsiella pneumonia to become antibiotic resistant when it acquires this enzyme
chemotherapeutic agents
-Medicine/chemicals used to treat disease
-Ie. heart meds
-Includes antimicrobials, antibiotics, synthetic drugs, and semi-synthetic drugs
antimicrobials
kill or inhibit microorganisms
antibiotics
-Antimicrobial drug synthesized by living organisms that kills bacteria
-Ie. penicillin derived from penicillium (a mold)
synthetic drugs
antimicrobial drugs chemically made in the lab
semi-synthetic drugs
-A normal, natural antimicrobial drug that is chemically modified in the lab to be better
-Ie. ampicillin and amoxicillin from penicillin
selective toxicity
-When a drug targets and kills the microbe but does not harm the host
-A drug targets structures and processes that are important for and unique to the microbe but aren't important for or present in the host
-The target in question could be peptidoglycan synthesis in bacterial cell walls, 70S ribosomes in bacteria, DNA replication, protein synthesis, and metabolic pathways
peptidoglycan synthesis inhibitors
-Disrupt the peptide cross links in bacterial cell walls, which compromises the structural integrity of the cell wall
-Penicillin G
-Ampicillin and Amoxycillin
-Cephalosporin
beta lactam ring
structural component of antibiotics (such as Penicillins) that enables an attack on the bacterial cell wall to stop peptidoglycan synthesis
Penicillin G
beta-lactam antibiotic that can only kill gram-positive bacteria
ampicillin and amoxicillin
semi-synthetic penicillins that can kill both gram-positive and gram-negative bacteria and can be taken orally
protein synthesis inhibitors
-Inhibit translation in bacterial cells by targeting 70S ribosomes
-Streptomycin
-Azithromycin
-Tetracycline
Streptomycin
aminoglycoside antibiotic that causes the tRNA to misread mRNA by changing shape of the smaller subunit to prevent the tRNA from matching up with mRNA properly, which results in abnormal proteins that are the wrong shape
Azithromycin
antibiotic that binds to the larger subunit of bacterial ribosomes to prevent mRNA movement through the ribosome
Tetracycline
-Antibiotic that blocks tRNA from docking in bacterial ribosomes, which halts protein synthesis
-Can kill gram-positive bacteria, gram-negative bacteria, chlamydias, and rickettsias
metabolic pathway inhibitors
-Inhibit folic acid synthesis in bacteria, causing cell death since folate is a precursor for DNA and RNA
-The folic acid pathway in bacteria is a multi-step pathway, the first step of which is to make para-aminobenzoic acid (PABA) into folic acid using enzymes
-Sulfonamides
Sulfonamides
antibiotic that serves as a competitive inhibitor of PABA for the active site of the first enzyme in folic acid synthesis
broad spectrum drugs
-Attack many different kinds of bacteria
-A complication is that these might also kill good bacteria
-Ie. Tetracyclines
narrow spectrum drugs
-Attack specific kinds of bacteria
-Ie. Penicillin G (attacks only gram-positive bacteria), Isoniazid (can only kill TB)
antiviral drugs
-Creating antiviral drugs is harder because it is hard to target the virus without targeting the host since the virus uses the host cell's machinery to copy itself
-Mechanisms of action include blocking attachment and penetration, blocking transcription and translation of viral molecules, and preventing maturation
Remdesivir
the first drug used against COVID-19 that targeted replicase (RNA dependent RNA polymerase)
intrinsic resistance
-The drug would have never gotten into the bacterial cell in the first place
-"It was just never meant to be."
acquired resistance
resistance that develops when bacterial cells share genes with each other
chromosomal mutation
-A mistake during DNA replications changes a gene to cause resistance to an antibiotic
-Vertical transfer
vertical transfer
antibiotic resistance gene moves from the parent cell to the offspring
horizontal gene transfer
-Genes come from a non-parent cell
-Includes transformation, transduction, and conjugation
transformation
a type of horizontal gene transfer in which bacteria picks up a piece of naked DNA (DNA not in a cell) from its environment
transduction
-A type of horizontal gene transfer in which a bacteriophage transfer DNA to another bacterial cell
-Occurs because sometimes bacteriophages are assembled with bacterial DNA instead of phage DNA
conjugation
a type of horizontal gene transfer in which a pilus forms between two bacterial cells and plasmids transfer from one cell to another via the pilus
mechanisms of drug resistance
-Impermeability of membranes
-Pumping out antibiotics more quickly via efflux pumps
-Cutting up antibiotics using enzymes (ie. beta-lactamase cutting the beta-lactam ring of penicillin)
-Changing the shape of the proteins that are targeted by the antibiotic
superinfection
-Occurs when an antibiotic kills off good bacteria in the microbiota, giving bad bacteria the opportunity to overgrow
-Ie. Candida albicans after a UTI in the urogenital tract, C. diff in the GI tract
-Occurs primarily with broad spectrum drugs
how resistance spreads
-Antibiotics kill susceptible bacteria but not the resistant ones, so the resistant ones survive and then multiply, passing on antibiotic resistance
-This is why people need to avoid exposure to antibiotics as much as possible and also why it is bad to stop using antibiotics before treatment is complete