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MICR 271 Module 5
Terms in this set (79)
Module goal: Explain how secretion of protein substrates to the cell surface differs from secretion to the external environment
Module goal: Explain how bacteria transmit a signal from a stimulus from the outside to the inside of the cell and the outcome of that signaling
-lots of these systems
-generally have a receptor in the membrane which send a signal to a responder in the cytoplasm which changes conformation and goes to a promoter gene to up or down regulate
Module goal: Explain the difference between beneficial, opportunistic, and pathogenic infections
beneficial = helpful
opportunistic = if IS is down, will proliferate
pathogenic = causing disease state
Module goal: Understand how viruses use host mechanisms to establish infection
can cause cancer
Module goal: Discuss specific examples to demonstrate an understanding of the complexity of microbial interactions with the environment
Module Goal: Discuss specific examples to demonstrate an understanding of the complexity of microbial interactions with the human host
How do marine viruses contribute to the coral reef ecosystem?
viral mediated lysis of hosts releases dissolved organic matter (DOM) and particulate organic matter (POM) in to the water column making them available for other microorganisms and coral
What are some extreme conditions microbes have been found in?
The dry valleys of Antarctica (windiest, coldest, driest ecosystem known)
What effects can microbes have on a plant and their rhizosphere?
most plant microflora found near roots.
can be commensal, pathogenic, or beneficial.
Can help attain nutrients from soil, protect from drought (forming a biofilm around roots), can also protect from viruses.
Give 2 examples of microbiomes effecting organism behaviour.
Give 2 examples of organism behaviour effecting the micro biome.
microbiota on human skin can effect how attractive the person is to mosquitoes- could impact disease spread
a certain bacteria abundance in mice can effect anxiety levels of the mouse
Green iguanas eat soil or feces to tailor gut microbiota to their diet.
some squid eject bioluminescent bacteria on the daily to control their symbiont populations
What is the Earth Microbiome Project and how could the data be useful.
established in order to try to determine where and what types of microbes exist on Earth.
It is estimated that less than 5% of the earth's microbiome has been cultured
this project collects the genomic sequences of many organisms from samples (viral, prokaryotic, eukaryotic). They won't know what they're sampling but they'll have a database of genomic sequences that could be used later to create technologies.
What are some ways biofilms negatively effect society?
biofouling on marine transport and equipment -> more fuel needed bc increased drag, corrosion, invasive species are carried
Medical devices: biofilms can form streamers (not attached to walls) and hinder fluid flow in devices such as catheters and stints
Microorganisms that reside in or on the body without causing disease, introduced at birth.
aka commensal organisms
when is normal flora established?
The first 3 years of life are highly influential for your gut microbiome
flora found in babys gestational environment (placental tissue etc.). They also pick some up from their delivery and from mum gut flora. within a couple hours mouth and nose flora are established and within a day the gut microbiota is established.
what factors can influence the makeup of a babies microbiome?
are fungi more diverse on skin or in internal environments on the human body?
internal environment on mucosal surfaces
which type of organism fluctuates the most in terms of genera composition of the normal microbiota?
fungi composition fluctuates the most
what can prolonged antibiotic treatment lead to?
fungal infections (mostly expansion of the Candida species)
can viruses be commensal organisms?
perhaps? they are found in asymptomatic people. unclear if they are helpful or harmful
The composition of commensal microbes in the human gut is directly influenced by:
c. geographical location
e. all of the above
health, diet, geographical location
The composition of commensal microbes in neonates is influenced by:
a. gestational age
b. delivery method
c. food source
e. age of mother
g. antibiotic treatment
h. all of the above
gestational age, delivery methods, food source, sanitation, antibiotic treatment
In which time period is human gut flora most susceptible to changes that result in established, individual microbiomes:
a. before birth
b. as a neotate
c. the first 3 years of life
d. up to adolescence
e. up to adulthood
c. first 3 years of life
In humans, where is the highest diversity of commensal fungi located?
b. mucosal surfaces
c. evenly distributed throughout body
d. humans don't have commensal fungi
b. mucosal surfaces
benefits of microbiome
-protection from predators and IS
-commmunication, resource sharing, HGT
-can create sub populations (division of labour) sophisticated division of labour
what signalling molecule is used for both intraspecies and interspecies communication?
Autoinducer 2 (AI2)
increased amounts of AI2 releasing from growing communities attracts others to the site
we are made up of ___ times more microbial cells than human cells as there is ____ times more microbial genes than human genes.
we are made up of 10 times more microbial cells than human cells as there is 100 times more microbial genes than human genes.
what are some normal flora found in the upper respiratory tract? skin? GI tract? Genital tract?
respiratory: staphylococcus and streptococcus
GI: E coli., streptococcus, lactobacillus
genital tract: lactobacillus, streptocuccus
two component systems (TCS)
bacterial sensing system to detect changed in env
-uses series fo phosphorylation-dependent, post-translational, activation events
-receptors = Histidine kinase (stimulus specific membrane bound proteins)
-response regulators in cytoplasm move to chromosome to affect gene transcription
which protein receptor is used in TCS?
-stimulus specific membrane bound proteins
what are the steps of the TCS signalling pathway?
1. environmental stimuli (molecules, pH, temp)
2. periplasmic (outside of cell) domain of the Histidine kinase receives signal = phosphorylation of cytoplasmic domain on histidine residue (sense histidine kinase)
3. phosphate transferred to response regulator specific to that histidine kinase protein
4. aspartate AA on receptor protein accepts the phosphate
5. configuration of response regulator altered to be a transcriptional activator or repressor depending on interaction with specific gene promoters
6. often leads to the secretion of things (proteins, toxins, siderophores, etc.)
secretion system for gram POSITIVE bacteria to move large particles onto cell surface
Sortase. what is the most conserved (similar across species) sortase enzyme?
enzyme that attaches wall associated proteins to cell wall
what 3 motifs must be on a Sortase proteins in order for it to be recognized by the Sortase system?
Signal peptide (specific series of AA at the N terminus of protein)
-cleaved off during passage through the membrane
Sorting Signal (LPXTG, series of AA, close to the c terminus)
AA's (+ charge) @ C terminus
-anchors protein to the membrane until the Sortaze enzyme is finished
what are the steps of Sortase-mediated secretion?
1. directed by the signal peptide, sortase substrate anchors onto the cytoplasmic membrane via the + charge C terminus
2. sortaze enzyme recognizes the LPXTG motif
3 sortase cleaves protein substrate
4. sortase transfers the protein substrate to a lipid intermediate using a peptide cross bridge component of the PG
5. the protein/ lipid complex is incorporated into the PG
exotoxin and example
A poisonous protein secreted by certain bacteria.
bacteria strain Clostridium releases
endotoxin and example
A toxic component of the outer membrane of certain gram-negative bacteria that is released only when the bacteria die.
gram neg bacteria lipopolysaccharide (LPS)-> release into bloodstream can cause endotoxic shock during septicaemia (blood poisoning)
Type 1 secretion system
gram neg bacteria secretion system of exotoxin. Proteins line up to make a channel
give an example of an exotoxin that can lyse red blood cells
Haemolysin released by some streptococci
-uses type 1 secretion
-toxin monomers assemble in donut formation around RBC, complex inserts itself into the RBS membrane where the shape changes creates a pore that releases the contents of the RBC
Type Three Secretion System (TTSS)
-injecting effector proteins directly into host cell
-evolved from flagella structure
3 basic benefits of the human microbiome
1. protection from pathogens (first line defence- colonization resistance)
2. nutrient aquisition (produce vitamins, break down food to extract nutrients)
3. immune system development (train and maintain)
-spores reside in the GI tract
-dont germinate bc other microbes keep them in check
-can occur when receiving prolonged antibiotic treatment (or taking many of them) that harms the rest of the microbiome-> but C Dif thrives (thus contributes to dysbiosis).
-produce potent toxins
-causes diarrhea, pseudomembranous colitis, death
-mainly treated with Fecal microbiota transplant
Fecal Microbiota Transplant (FMT)
-can be used to treat Crohns, C.difficile
-taking microbiome samples from fecal matter of others and transplanting it into a sick person
our gut microbiome provides us with a significant source of what vitamin? what microbe is a key producer of this vitamin?
-we cant make it
-exclusively made by microbes
-uses ~30 genes to make the B12
what characterizes a normal microbiome?
high levels of diversity and number of microbes
what characterizes a perturbed microbiome?
decrease in level of diversity and number of microbes
what characterizes a dysbiosis in a microbiome?
long term decrease in diversity, numbers may still be high
pathogens like C. difficile take over
the quality or state of being able to overcome bodily defence mechanisms and a measure of the severity of an infection.
ability of an organism to cause disease
virulence and pathogenicity are measures of _______________________ interactions between the host and microbe.
what are some examples of viral pathogens? bacterial pathogens?
- Viruses that lead to cancer
An organism that causes disease
a chronic, progressive viral infection that damages the immune system
-specifically targets CD4 T cells
-depletes CD4 numbers
-vulnerable to wide range of infection (AIDS)
how does HIV cause a depletion of CD4 cells?
due to the immune response to the infection
-infected cells stimulate cytokine production = immune activation
-this causes activation-induced cell death of CD4 cells driven by chronically activated and hyper inflammatory immune state
can viral infections lead to cancer?
yes some can
eg: papillomaviruses, Epstein-Barr, hepatitis B
cancer causing gene- altered DNA from its original form as a promo-oncogene.
the uncontrollable division of host cells caused by infection with a DNA tumor virus
what are 2 ways a retrovirus can lead to cancer?
1. package host DNA into viral progeny
-can carry a segment of host DNA to the next host
-can mutate genes into oncogenes
2. Alteration of protein expression
-after viral genes are in host genes there can be uncontrolled growth of infected cell
An RNA virus that reproduces by transcribing its RNA into DNA and then inserting the DNA into a cellular chromosome; an important class of cancer-causing viruses.
Pathogenic E. coli
-use Type III secretion to inject proteins into host cell that promote adherence of the bacterium to the cell surface (called pedestal formation)
what are the steps of type III secretion pathogenic E.coli uses to infect host cells?
1. secretion machinery assembled (needle)
2. Tir (bacterial protein) injected into membrane of host cell
3. bacterium moves closer and Tired dock with intimin on bacterial surface = firm attachment
4. host cytoskeletal proteins are recruited forming a pedestal basest the cell surface
What mechanism does E.coli use to attach to host cells?
Type III secretion to complete pedestal formation which allows firm attachment to host cell
what does the Type III secretion and pedestal formation of E.coli attachment to a host cell look like?
a moon landing
inserts tube to inject Tir
Tir nestle in host cell surface and act as landing pads for the intimin protein on bactiera
Houston we have contact
actin form polymers in host cells from the Tir protein ends-> creates bump that raises the bacterium up on a throne
tooth decay caused by cariogenic species.
-there is an underlying healthy presence of microbes
-the environmental shift in the mouth leads to favouring tooth decay causing microbes
-One of several common bacteria that can cause nail, wound, eye infection and are commonly found in health care institutions
-biofilms are important to establish infection
- primary cause of MORTALITY in cystic fibrosis patients
Steps of biofilm formation
1. planktonic mode of growth
1. reversible attachment, individual cells populate the surface
2. irreversible attachment: Extracellular polymeric substance (EPS) is produced
3 & 4. Maturation (stage 1 and 2) Biofilm architecture develops and matures
5. Single cells are released from the biofilm
what is the difference between quorum sensing and two component systems (TCS)?
what are the steps in Pseudomonas aeruginosa biofilm formation
uses 3 TCS systems during biofilm formation
reversible -> irreversible attachment (Bfir/S-P used)
irreversible-> maturation 1 (BfmR/S-P)
Maturation 1 -> maturation 2 (Micr/S-P)
what is the primary cause of mortality in cystic fibrosis patients? why?
Pseudomonas aeruginosa (opportunistic pathogen)
-excess mucus facilitates survival of bacteria
-antibiotics decrease numbers but few survive and become genetically diverse and resistant to antibiotics and male Dif types of biofilms to enhance survival
-persistant bacterial infection = inflammation = damaged tissue = decreased pulmonary function
A genetic disorder that is present at birth and affects both the respiratory and digestive systems. buildup of mucus in lungs
an acute diarrhoeal infection caused by ingestion of contaminated water or food with Vibrio cholerae
-yearly 1.3-5 million cases and 21-120 thousand deaths
-secretes toxin that disrupts the salt and water balance of the intestine = diarrhoea
-depends on biofilm production at different life stages
treatment of cholera
replace fluids, administer antibiotic
Theres a vaccine...but this is still a significant issue in developing countries where sanitation and drinking water cleanliness is an issue
incidence of a specific notifiable disease
the state of being subject to death
describe the V. cholerae infection cycle
depends on biofilm production at various life cycle stages.
-biofilms on plankton and sediments
ingestion by host
-clumps of bacteria adhere to intestinal epithelium vis adhesive pili (TCP)
-toxin and TCP production are coregulated in response to the ionic environment of the intestinal lumen
Release in stool
chain of infection
factors that lead to the transmission or spread of disease. microbe with significant virulence exposed to host in high enough dose.
breaking any links in the chain can prevent infection (ex: vaccination breaks susceptibility)
pathogen -> virulence -> exposure-> dose -> susceptibility
microorganisms transferred from an inanimate object (door, table, medical equipment)
can asymptomatic ppl with CoV-2 transmit the virus
is the use of masks alone enough precaution to protect one from CoV-2?
no, should also social distance
how is SARS-CoV-2 transmitted
that transmission of SARS-CoV-2 occurs primarily between people through direct, indirect, or close contact with infected people through infected secretions such as saliva and respiratory secretions, or through their respiratory droplets, which are expelled when an infected person coughs, sneezes, talks or sings.
Respiratory droplets from infected individuals can also land on objects, creating fomites (contaminated surfaces).
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