Exam 1 Flashcards
a bacterial, viral, or fungal agent of disease
pathogen
a method to amplify DNA in vitro using many cycles of DNA denaturation, primer annealing, and DNA polymerization using a heat-stable polymerase
polymerase chain reaction (PCR)
a living organism that requires a microscope to be seen
microbe
the sum of all genomes of all members of a community of organisms
metagenome
a noncellular particle containing a genome that can only replicate inside of a cell
virus
cells lacking a nucleus; includes bacteria and archaea
prokaryotes
cells with a nucleus
eukaryotes
the three domains
bacteria, archaea, eukarya
the total genetic information contained in an organism’s chromosomal DNA
sequence of all the nucleotides in a haploid set of chromosomes
genome
what does the genes in a microbe’s genome and the sequence of DNA tell us about
how that microbe grows and associates with other species
microbial capabilities are defined by genome sequences
organisms exist in both _________ and ___________ forms
macroscopic and microscopic
major categories of microbes include
bacteria
archaea
microbial eukaryotes
viruses
microbes may grow in
communities, such as a biofilm
includes all the microbes that live on or in us
may be commensalism or mutualism (mostly)
mostly harmless microbes but can cause problems sometimes
the human microbiome
what parts of the body would not be included in the human microbiome
blood, cerebrospinal fluid, internal organs
true or false: the composition of the human microbiome is unique to each individual
true
what are the 3 domains
bacteria, archaea, eukarya
humans harbor diverse species from a limited number of __________: Actinobacteria, Bacteriodetes, Firmicutes, Fusobacteria, and Proteobacteria
phyla
what do microbiome differences arise from
genetics, age, lifestyle, environment, etc
proportions of microbes in the microbiome are heavily influenced by
anatomical site
your microbiome begins developing at birth and reaches a ________ state by age 3
stable
what are some factors that can fluctuate your microbiome
puberty, weight changes, diet, pregnancy, stress, cohabitation, new pets, job changes, children, medications, sports, travel, menopause
an imbalance in the microbial community that is associated with diseases
dysbiosis
animals that are used to direct physiological impact of the microbiome, allowing us to prove causation
gnotobiotic animals
all microbes are known, includes germ-free
gnotobiotic
an increase in Firmicutes would result in
obesity
a decrease in bacteroidetes is associated with
obesity
a decrease in verrucomicrobia is associated with
obesity
an increase in actinobacteria is associated with
obesity
a decrease in F. prausnitzii results in
obesity
disadvantages of using a germ-free animal
- more susceptible to pathogens
- poorly developed immune system
- lack key nutrients
- lower cardiac output, thin intestinal walls, and altered behavior
failure of immunoregulation is due to inadequate exposures to the microorganisms that drive development of the immune system
old friends hypothesis
the process by which pathogens produce disease
pathogenesis
a microbe that causes disease
pathogen
causes disease in a healthy host; can breach host defense mechanisms
primary pathogens
causes disease only in immunocompromised hosts or in specific circumstances
opportunistic pathogens
started the notion of handwashing
Ignaz Simmelweis
theory that states that microbes can cause disease
germ theory
koch’s postulates establish a __________ relationship between a microbe and a specific disease
causative
koch’s postulates (4)
- the microbe is found in all cases of the disease but is absent from healthy individuals
- the microbe is isolated from the diseased host and grown in pure culture
- when the microbe is introdued into a healthy, susceptible hsot, the same disease occurs
- the same strain of microbe is obtained from the newly diseased host
a complex bidirectional network of communication between the Central Nervous System, the intestine, and the intestinal microbiota
microbiome-gut-brain axis
which cranial nerve is an important part of the microbiome-gut-brain axis
the vagus nerve
neurochemicals made by the brain initiate efferent vagus nerve impulses that travel from the brain to the gut, whereas gut bacteria make neurotransmitter-like chemicals that acan fire afferent signals back along the axis to the brain
the serial passage of a pathogenic organism from an infected individual to an uninfected individual, thus transmitting disease
chain of infection (transmission of disease)
a culture containing only a single strain or species of microorganism
pure culture
a visible cluster of microbes on a plate, all derived from a single founding microbe; usually consists of a clone, except for infrequent mutations
colony
exposure of an individual to a weakened version of a microbe or microbial antigen to provoke immunity and prevent development of disease upon reexposure
vaccination
a body’s resistance to a specific disease
immunity
an organism’s cellular defense against pathogens
immune system
the stimulation of an immune response by deliberate innoculation with a weakened pathogen, in hopes of providing immunity to disease caused by the weakened pathogen
immunization
a chemical that kills microbes
antiseptic agent
free of microbes
aseptic
a molecule that can “kill” or inhibit the growth of selected microorganisms
antibiotic
provide a set of criteria to establish a causative link between an infectious agent and a disease
Koch’s postulates
established the practice of vaccination, or inoculation with cowpox to prevent smallpox
Edward Jenner
developed the first vaccines that were based on attenuated strains
Louis Pasteur
showed that antiseptics could prevent the transmission of pathogens from doctor to patient
Ignaz Semmelweis and Joseph Lister
discovered that the Penicillum mold generates a substance that kills bacteria
Alexander Fleming
purified the substance penicillin, the first commercial antibiotic to save human lives
Howard Florey and Ernst Chain
discovered viruses as filterable agents of infection that aren’t cells
Dmitri Ivanovsky and Martinus Beijerinck
first crystallized viral particles
Wendell Stanley
a period of the infection process during which a pathogenic agent is dormant in the host and cannot be cultured
latent state
an organism’s ability to cause disease
pathogenicity
how easily an organism causes disease
infectivity
a measure of the degree, or severity of disease
virulence
a measure of virulence; the number of bacteria or virions required to kill 50% of an experimental group of hosts
Lethal Dose 50% (LD50)
the route of transmission an organism takes
infection cycle
two main forms of transmission
horizontal transmission and vertical transmission
a mode of transmission in which an infectious agent is transferred from one person or animal to the next
horizontal transmission
a mode of transmission whereby the agent is transferred from an infected parent to offspring
vertical transmission
how can vertical transmission occur in humans
transplacental transmission or during birth
the process by which certain pathogens in maternal blood can pass through the placenta and infect the fetus
transplacental transmission
modes of horizontal transmission (5)
direct contact
airborne transmission
indirect contact
vehicles
vectors
pathogens that spread horizontally from person to person by physical contact with skin, blood, or bodily fluids
direct contact
in disease, the transfer of a pathogen via dust particles or on respiratory droplets produced when an infected person sneezes or coughs
airborne transmission
a broad term that covers all types of transmission that are not directly passed from person to person (fomites, food, and water)
indirect contact
an inanimate object on which pathogens can be transmitted from one host to another
fomites
the transfer of a pathogen when an infected person deposits it on a surface or in food or drink that another person touches or consumes
vehicle transmission
an organism that maintains a virus or bacterial pathogen in an area by serving as a high-titer host
reservoirs
a vector that conveys pathogens to a susceptible individual or food without the pathogen needing to replicate in the vector
mechanical vector
an infectious disease that is primarily seen in animals but can be transmitted to humans either by vector or other means
zoonotic disease
the transfer of a pathogen from parent to offspring via infection of the egg cells
typically seen in insects
transovarial transmission
a person who harbors a potential disease agent but has no symptoms of disease
asymptomatic carrier
portals of entry
respiratory
oral
ocular
urogenital
parenteral
wound
agents that are transmitted only by mosquitos or ticks; injection into the bloodstream
parenteral route
applies when the immune response to a pathogen is a contributing cause of pathology and disease
immunopathogenesis
a trait of a pathogen that enhances a pathogen’s disease-producing capability
toxins, attachment proteins, capsules, and other devices used by pathoge
virulence factors
true or false: if you become infected with a pathogen, you will become diseased
false
what are the requirements for Molecular Koch’s Posulates
- the phenotype under study should be associated with pathogenic strains of a species
- specific inactivation of the suspected virulence gene(s) should lead to a measurable loss in virulence or pathogenicity. the genes should be isolated by molecular methods
- reversion or replacement of the mutated gene should restore pathogenicity
an organism that can carry infectious agents from one animal to another
vectors
a type of genomic island in which the stretch of DNA contains virulence factors and may have been transferred from another genome
pathogenicity island
a measure of how easily a disease spreads
basic reproduction number (R0)
replication of pathogen in host
infection
factors that influence infection after exposure
(host and pathogen) genetics
risk factors to developing disease
prior exposure to pathogen
measures the proportion of infected people who develop disease
case-to-infected ratio (CI)
how do you calculate R0
determine the ratio of new cases to existing cases
a measure of virulence
case-fatality-ratio (CFR)
what is the CFR equation
CFR = M / (Ir + Ip + Id)
M= mortality
Ir = infected + recovered
Ip = infected and presented
Id= infected and died
what does a pathogen need to do to cause disease
- make contact w/ appropriate host tissues/cells
- outcompete the resident microbiota for resources
- survive host defense mechanisms
- multiply and eventually transmit to a new susceptible hsot
how do we identify virulence factors?
- compare genomes of related virulent/avirulent pathogens
- identify genes in the virulent strain that are absent from a virulent strain
- use molecular koch’s postulates
used to prove a gene encodes a virulence factor
molecular koch’s postulates
measures the dose that it takes a microbe to cause infection (but does not kill host)
infectious dose 50 (ID50)
form, elevation, margin, size, texture, and opacity
colony characteristics
bacteria arranged in a spherical shape
coccus (pl. cocci)
cocci cells are arranged based on what
plane of cell division
chains of spherically shaped cells
streptococcus
grapelike clusters of spherically shaped cells
staphylococcus
rod-shaped cells
bacillus (pl. bacilli)
rigid, short spiral-shaped cells
spirillum (pl. spirilla)
flexible, long spiral-shaped cells
spirochetes
comma-shaped cells
vibrio (pl. vibrios)
most bacteria are typically between what size in length?
0.5-5.0 micrometers
what are the constraints on small cells?
cells must be big enough to have essential genetic material and machinery
smallest known bacterial cells
0.2 micrometers
smallest known genomes (~650 genes)
Mycoplasma
cannot reproduce outside their host cell, meaning that the parasite’s reproduction is entirely reliant on intracellular resources
obligate intracellular parasite
large cells are constrained by the limits of
diffusion
how does E. fishelsoni compensate for its large size?
- with a highly folded membrane that increases surface area
- multiple genome copies to make materials at different locations
- vesicles help to excrete waste
includes everything that surrounds the cells cytoplasm
(plasma membrane, cell wall, specialized outer layers)
cell envelope
how do bacterial cell membranes closely resemble eukaryotic cell membranes
- regulate traffic
- detect signals from the environment
- contains cholesterol-like structures to help maintain membrane fluidity
cholesterol-like structure in bacteria that helps maintain membrane fluidity
hopanoid
fatty acid chain saturation change in response to what stimuli
temperature and pH
saturated fatty acid chains can pack very tightly and are more present in what environment
hotter
unsaturated fatty acid chains are present in what type of environment
contain kinks due to cis bonds
cooler environments
cyclopropane fatty acids help resist what type of change and how do they maintain this?
- pH
- decrease permeability of membrane to protons, helping bacteria to survive in acidic environments
some archaeal membranes are ______________ that withstand very high temperatures
monolayers
the bacterial cell wall is made up of
peptidoglycan
the bacterial cell wall helps prevent lysis in what type of tonic environment?
hypotonic
qualities of gram positive bacteria
- stains purple
- teichoic acids
- many layers (up to 30) of peptidoglycan
- only one membrane
qualities of Gram negative bacteria
- Lipopolysaccharides
- stains pink
- inner and outer membrane with a periplasm in the middle
- 1 or 2 layers of peptidoglycan
- porins
- lipoproteins
scaffolds for enzymes that remodel peptidoglycan in Gram-positive bacteria
teichoic acids
what are lipopolysaccharides (LPS) composed of? (most internal to external)
- Lipid A
- Core polysaccharide
- O antigen
why is LPS a virulence factor?
- the composition of the O-antigen varies in different strains, making it resistant to host defense mechanisms
- Lipid A is an endotoxin (can overactivate immune response, leading to organ failure and septic shock)
steps to Gram-staining
- crystal violet
- iodine
- ethanol
- safranin
the cell wall has what type of charge
negative
crystal violet has what type of charge
positive charge
safranin has what charge
negative
what genera of bacteria are Gram positive?
- Staphylococcus
- Streptococcus
- Listeria
- Clostridium
what genera of bacteria are Gram-negative
- Neisseria
- Escherichia
- Salmonella
- Campylobacter
- Borrelia
- Treponema
- an organized, crystalline-like layer of protein or glycoprotein found in archaea and bacteria
- contributes to cell shape and helps protect cell from osmotic stress, bacteriophages, and predatory bacteria
S-layer
- a well organized layer of polysaccharides, tightly associated
- acts as a virulence factor and adheres to surfaces and host cells, aids in biofilm formation, protection from dessication, evasion of phagocytosis by white blood cells
capsule
- diffuse, unorganized layer of extracellular material (polysaccharides, glycoproteins, glycolipids); loosely associated
- adheres to surface and host cells, aids in biofilm association, protection from dessication, evasion of phagocytosis by white blood cells
slime layer
virulence factors that help bacteria form biofilms
capsules and slime layers
specialized, surface-attached, collaborative communities that are hard to treat
biofilms
how do nutrients cross the cell membrane in gram positive cells
- simple diffusion
- facilitated diffusion
- active transport
use ATP directly to move molecules against their electrochemical gradient
primary active transport
steps to primary active transport
- solute binds to its cognate periplasmic binding protein, and the complex then binds to the membrane transporter
- the ATPase activity of one component powers the opening of the channel and movement of the solute into the cell
what is an example of primary active transport
ABC (ATP-Binding Cassette) Transporters
use the energy stored in a gradient (one molecule moving from high-to-low) to transport molecules
secondary active transport
examples of secondary active transport
symporters and antiporters
- a mechanism of transport across a membrane in which two different molecules move in the same direction
- one molecule moves up the electrochemical gradient because the movement of the other molecule is more favorable
symporters
- membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane
- the movement of one ion or molecule is against its electrochemical gradient and is powered by the movement of another ion or molecule with its electrochemical gradient
antiporters
- a bacterial active transport mechanism that uses metabolic energy
- goes down the electrochemical gradient in a favorable way
- unique to bacteria
group translocation
example of group translocation
phosphotransferase system (PTS)
how do nutrients from the environment enter Gram negative cells?
- through the outer membrane: porins and TonB-dependent transporters
- through the inner membrane: same as Gram positive cells
- passive water-filled pores that have less specificity
- act via facilitated diffusion
- allows small (<600 Da) solutes to diffuse, driven by their concentration gradient (from high to low) [ex: amino acids and glucose]
porins
- active transporter
- energy intensive
- undergoes a conformational change
- used for very limited nutrients (high specificity and affinity)
- linked to inner membrane via TonB
- needs another active transporter
TonB-dependent receptor
TonB-dependent receptors use energy from
proton motive force transmitted from inner to outer membrane
the force that promotes movement of protons across membranes down the electrochemical gradient
proton motive force
- often a limiting nutrient
- a key part of the ETC and an important cofactor for certain enzymes
iron
have an extremely high affinity for iron, function primarily to scavenge iron
siderophores
siderophores utilize what type of transport
ABC transporters
active
steps to iron transport
- the siderophore called enterochelin is secreted and binds iron
- the complex is transported to the periplasm through an outermembrane protein FepA
- a periplasmic binding protein escorts the complex to an ABC transporter
- the enterocherlin-iron complex enters the cell
- inside the cell, the iron is released and reduced to iron
specialized appendages of bacteria
- pili/fimbriae
- sex pili
- flagella
- protein-based (pilin) finger-like appendages
- responsible for adherence
- can act as a virulence factor
pili / fimbriae
- thin protein appendage
- connects cells during conjugation (horizontal gene transfer)
sex pilus
- not common in coci
- rigid spiral filament of protein monomers called flagellin, extends from the cell surface
- responsible for cell motility powered by proton motive force
- spins like a propeller
flagella
spirochetes have what kind of flagella
endoflagella
- wraps around cell body within periplasm
- better at moving through viscous envronments
endoflagellum
bacteria house their DNA in what rather than a defined nucleus
nucleoid region
what allows for the condensing of DNA into a nucleoid region
DNA-binding domains
critical for cell shape and division
bacterial cytoskeleton
- forms a ring inside almost all bacteria
- tubulin homolog
- critical for cell division
- responsible for contraction and separation, remodeling of peptidoglycan
FtsZ
- forms a coil inside rod-shaped and elongated cells
- actin homolog
- critical for cell shape determination
MreB
- forms a polymer along the inner side of crescent-shaped bacteria
- intermediate filament homolog
- critical for cell shape determination
crescentin (CreS)
- protein “vesicles” filled with air
- provide buoyancy to cells for movement in response to light and nutrients
- present in aquatic organisms/photosynthetic bacteria
gas vesicles
- protein “vesicles” that contain CO2 and RubisCO
- responsible for carbon fixation
carboxysomes
- built when carbon sources are abundant / responsible for carbon storage
- store nutrients in nutrient-limited environments
- lipid polymers
inclusion bodies (PHB granules)
- consist of magnetite enclosed by a lipid membrane
- directed motility based on a magnetic field (magnetotaxis)
magnetosomes
- dormant structure composed of DNA, ribosomes, and severall tough protective coverings
- ensure survival through periods of environmental stress
endospores
how has human control of infectious disease made incredible progress in the last century?
- improvements in sanitation and hygiene
- antimicrobial drugs (antibiotics, antifungals, antivirals)
- vaccines
compounds produced naturally in nature that adversely affects other microbes
antibiotics
harms target organism but does not affect humans; drug should affect microbial physiology that does not exist, or is greatly modified in humans
selective toxicity
antibiotics that target cell wall synthesis
- penicillins
- cephalosporins
- bacitracin
- vancomycin
antibiotics that target protein synthesis
- chloramphenicol
- tetracyclines
- aminoglycosides
- macrolides
- lincosamides
antibiotics that target cell membrane integrity
- polymyxin
- daptomycin
- amphotercin
- imidazoles (fungi)
these drugs are typically topical agents
antibiotics that target nucleic acid function
- nitroimidazoles
- nitrofurans
- quinolones
- rifampin
- some antiviral compounds, especially antimetabolites
antibiotics that target intermediary metabolism of bacteria
- sulfonamides
- trimethoprim
antibiotics can typically be classified as
- broad spectrum
- narrow spectrum
a type of antibiotic that targets a wide range of microbes
broad spectrum
a type of antibiotic that has a narrow range of the organisms they affect
narrow spectrum
in regards to arresting bacteria/killing them, antibiotics can be classified as
bacteriostatic or bactericidal
- does not lyse cell and prevents septic shock form gram negative cells
- not very useful if pt is immunocompromised
- arrests growth, does not kill bacteria
- gives immune system time to catch up
bacteriostatic antibiotics
- lyses cell
- kills bacteria
- brings potential for lipid A toxicity
bactericidal drugs
- NAG and NAM precursors are made in the cytoplasm
- they are carried across the cell membrane by a lipid carrier: bactoprenol
- precursors are polymerized to the existing cell wall structure by transglycosylases
- the peptide side chains are cross-linked by transpeptidases
peptidoglycan synthesis
drugs that target peptidoglycan are typically seen as
bactericidal
what drug inhibits NAG and NAM precursors from being made in the cytoplasm
cycloserine
what drug prevents NAG and NAM precursors from being carried across the cell membrane by bactoprenol
bacitracin
what part of penicillin chemically resembles the D-Ala-D-Ala part of peptidoglycan
B-lactam ring
mechanism of penicillin
- target bacterial penicillin binding proteins (PBP)
- interfere with transpeptidation (D-Ala-D-Ala is the substrate of transpeptidase)
- competitive and irreversible covalent bond forms
- unstable cell wall
- cell death
active against gram positive bacteria
penicillin G
active against gram positive bacteria and is acid resistant
penicillin V
B-lactamase resistant
methicillin
active against a broad range of bacteria
- carbenicillin
- amoxiciliin
active against a broad spectrum of bacteria and is acid resistant
ampicillin
- antimetabolites that interfere with bacterial metabolism
- bacteriostatic
sulfa drugs
static drugs that interfere with the bacterial ribosome
- macrolides (erythromycin and azithromycin)
- chloramphenicol
- tetracyclines (doxycycline)
block transfer of the peptide
macrolides (erythromycin and azithromycin)
obstructs formation of the peptide bond
chloramphenicol
interfere with the binding of the tRNA with the mRNA codon
tetracyclines (doxycycline)
- interferes with elongation causing misreading
- produces junk proteins
- bactericidal
aminoglycosides (streptomycin and gentamycin)
how do bacteria become resistant to antibiotics
- prevent entry into cell or destroy antibiotic
- prevent binding to target by altering target or modifying antibiotic
- reverse binding by disoldging the antibiotic bound to target
how can antibiotic resistance be acquired from other microbes
horizontal gene transfer
- microbes that produce antibiotics in nature must also be resistant and competitors must have defense mechanisms
- have genes encoding resistance proteins
intrinsic resistance
selective pressure from what promotes survival of antibiotic resistant strains
overuse of drugs
bacteria exhibit a high frequency of
random mutations and recombination
