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MICROBIOME :house_buildings: (FECAL TRANSPLANTATION (method (husband's…
MICROBIOME :house_buildings:
HOW ACQUIRED
ORIGINAL
ORIGINAL BELIEF: sterile womb hypothesis
recent evidence reveals, bacteria are present in
umbilical cords blood
amniotic fluid
fetal membranes
found without any indication of inflammation
meconium - first newborn bowel - movement conatins bacteria
infants get an initial microbiome before birth
receive more through birth and breastfeeding
MICROBIAL TRANSMISSION
MOUTH :lips:
amniotic fluid oral origins
transmitted to the uterus thru blood
UTERUS
meconium contains bacteria (lactic acid bacteria)
assess thru vagina or bloodstream
VAGINA
different across ethnicities :pregnant_woman: :pregnant_woman::skin-tone-3: :pregnant_woman::skin-tone-6:
less diverse during pregancy
more lactobacillus
EXTERNAL BREAST :shirt:
INTERNAL BREAST :bikini:
symbiotic BACTERIAL pH
most bacteria - symbiosis : 6.5 - 7.5
molds + yeast : pH 4 and 6
pH < 4 : lactobacillus survives
lower pH protect host from opportunistic infection
at pH 4.5 : wild Candida
pathogenic - cause vaginitis
opportunistic infection - colonize host when lactobacilli are inhibited
NEWBORN NEW MICROBIOME
POST BIRTH ACQUISITION
MODE OF BIRTH DELIVERY :pregnant_woman:
METHOD OF STUDY
16S rRNA community sampling analysis - human gut
mostly bacteria of 2 phyla
firmicutes
bacteroidetes
archaea
methanobrevibater smithii
mode of delivery shape the acquisition and types of initial microbiota
Dominguez-Bello used 16S rRNA gene sequencing - examine microbiota from mothers and newborns
each dots represent duplicate of mother and baby
closer the dots, more similar
NATURAL DELIVERY
babies get microbiome that resembles mother's vaginal bacteria
increase in
lactobacilli
help ingest milk
urea excreted from the mother's milk can be broken down by lactobacilli
bifidobacteria / bacteriodetes
colonize gut microbiome
C-section
microbiome ressembles mother's skin
INOCULATION
METHOD
newborns receive an inoculum of vaginal microbiome right after birth
baby microbiome increase but doesn't reach the same level as natural delivery
reasons for not reaching the same diverity
lots of change during labor
cannot be restored by taking microbes from mother
DEFINITION
RESTORING VAGINAL MICROBIOME IN BABIES BORN VIA C-SECTION
bacteroidetes appears around 6 months of age
FEEDING METHOD :baby_bottle:
BREAST MILK
external breast
propionibacteria
corynebacteria
staphylococcus
internal breast
streptococcus
staphylococcus
serratia
lactococcus
transmitted thru lymph and blood and infant oral cavity
FORMULA MILK
not that many microbes
PRE BIRTH AQUISITION :pregnant_woman::skin-tone-2:
microbes from the womb - amniotic fluid
PERTURBATIONS
ANTIBIOTICS = Abx
correlation with problems
OBESITY
STUDIES
children BMI and antibiotics
AGE RANGE - 6 months; 6-14 months; 15-23 months
conclusion - early exposure (6 MONTHS) show increase in BMI
anytime later than that does not show anything
1100 children's BMI correlation with abx
analysis - SHAPE THE SPECIES OF BACTERIA PRESENT
RODENTS
early exposure showed increase in body mass, larger bone, gain more weight
murine microbiome was also altered with some bacteria grow better and other decrease
mice receive antibiotic within days when they're born
ANTIBIOTIC FOUND IN FOOD
STUDIES OF RODENT
obese mice - microbiome
:arrow_up: amount of enzyme to digest complex polysaccharides :arrow_right: fermentation :arrow_up:
:arrow_up: absorb short chain of fatty acid
microbiome from obese mice transplanted into germ free mice, germfree gain weight & extract more energy
esgosterol - found in membrane of yeast and fungi target molds
natamycin - found in the cheese to
target molds
DECREASE IN MICROBIOME -> decrease in immune response
ADULTS
microbiome - immediately lose diversity and shift in community composition within 3 or 4 days of drug initiation
ciprofloxacin triggered profound and rapid change in gut microbiome
stop drugs for a week :arrow_right: communities return in initial state :arrow_right: incomplete return
conclusion - Abx trigger profound effect change on gut microbiome
three healthy adults took ciprofloxacin
newborn vs. antibiotic
within 48 hours with antibiotic - newborn microbiota is less diverse
microbiota never fully recovered
ANTIBIOTIC RESISTANCE
MECHANISMS
production of enzyme the modify/destroy drugs
change drug binding target
prevent drug entry into the cell
efflux - pump drug back out of cell
REASON
long term use of single antibiotic
widespread antibiotic use
intact antibiotics present in environment
clinical dosage exceed MIC - minimum inhibitory concentration
different tissues/organs received sub-inhibitory or higher inhibitory concetrations
ANOTHER WAY to happen
horizontal gene transfer
intestinal lumen
intestinal epithelial cells
PERTURBATION - clostridium difficile
opportunistic pathogen
colonize host after long regime of antibiotics
strictly fermentative anaerobe microbe that form spores -> it survive the antibiotic horror
FIGHTING ANTIBIOTIC RESISTANCE
I. MORE POTENT ANTIBIOTICS ? - not likely, they'll outsmart us anyways
II. microbes vs. microbes
VIRUSES
BACTERIOPHAGES
STRUCTURE
CAPSID
protein shell surrounding the genome of the virus
has a number of protein molecules
arranged in precise and highly repetitive pattern around the nucleic acid
GENOME
contain only DNA
DNA replication (may have polymerase)
life cycle regulation
repressor, activators, integrases
lysis
2 more items...
well-characterized genes
5 more items...
structural gene
GP5 - major tail protein gene
LIFE CYCLE
LYTIC
first thing
4 more items...
LYSOGENIC
the virus genome is integrated into the host DNA
viral DNA survive by dividing with the host daughter's cell
TEMPERATE PHAGES
undergo both lytic and lysogenic
regulation
3 more items...
example: phage lambda
3 more items...
compare to bacteriophages
they can infect both gram + and -
penetrate both cell wall/ outermembrane
mechanisms
virions attach to cells via tail fibers
tail fibers retract and tail core (GP5) makes contact with cell wall
lysozyme-like (holins) enzyme forms pore in peptidoglycan
tail sheath contracts
viral DNA passes into cytoplasm
STUDIES IN VITRO
plaque assay
plaque - clear zones that develop on lawn of host cells
analogous to bacterial colony
one way to measure virus infectivity
1 plaque = 1 virus particle
electron microscopy
THERAPY
PROS
kill just one species/ strain
antibiotic kill the entire microbiome
1920 - used by Soviet and eastern europe
2013 - European commission funded Phagoburn- clinical trial of phage therapy for human infection
CONS
OVERVIEW
transduction
V.cholerae produces toxin whose gene obtain from virus
OVERVIEW
human microbiota consists of 100 times genes than humans
there are 100 phages/ bacterium
TYPE - insert the shapre
complex
mixture of icosahedral and filamentous shapes
many bacteriophages
asymmetrical/ irregular shapes
tend the be larger viruses
Ex: poxvirus
only infect bacteria cell
icosahedral- rhinovirus
roughly spherical in shape
most efficient arrangement of subunits in a closed shell
requires the smallest number of capsomere to build
20 triangular faces
ENVELOPED VIRUSES - hepatitis C
lipid envelop
derived from host
not encoded by viral genome
protein in the envelope may be from the virus
can fuse to host cell and organelle membrane
obligate parasite
helical - tobacco mosaic virus
MORE PROBLEMS
SUB-THERAPEUTIC CONCENTRATIONS
meaning - dose that is lower than the concentration that should inhibit / kill bacteria
trigger
SOS RESPONSES
triggered due to buildup ssDNA from cell damage
prophage induction - viral DNA incorporated in the host enter lytic cycle :arrow_right: transfer abx gene
ICE induction - integrative & conjugative elements carrying antibiotic resistance genes can be transferred via
conjugation
integron recombination - mobile cassettes that contain resistance gene
transposition - mobile elements can transpose in the chromosome :arrow_right: pass on to daughter cell
Rpos INDUCTION
sigma factor/ transcription factor
DNA poly IV : Error-prone DNA polymerase -> less checkpoint :check: -> more mutation -> more chance of getting antibiotic resistant gene
inhibition of mismatch repair
DNA polymerase IV is overly expressed :arrow_up:
DNA polymerase II is inhibited :forbidden:
what: bacterial cell stress response that induces transcription of certain genes involved in DNA repair
ANTIBIOTIC & ENVIRONMENT STUDIES
LECHUGUILLA CAVE - NEW MEXICO
for 4 milion years, location is isolated from
anthropogenic use of antibiotics
antibiotic contamination
Bhullar collected 92 bacterial strains from 3 sites
amplification of 16S rRNA gene to create phylogenetic tree :evergreen_tree:
all strains were tested in common antibiotic
identification
gram + and gram -
3
streptomyces
highly resistant to
daptomycin
(impairs cell membrane polarization)
daptomycin is fairly new drug
conclusion
not a lot of water in the cave
limit resources
microbes compete against each other :arrow_right: create abx to destroy others
microbes develop antibiotic resistance
YANOMAMI POPULATION
live in southern venezuela
has diverse microbiome - result from survival and adaptation
microbiome genes carry resistance to
natural antibiotic
synthetic antibiotic
FECAL TRANSPLANTATION
effective to treat clostridium difficile
-Dr, Khoruts - first physician to do fecal transplant
PURPOSE - restoration of normal gut microbiome
efficient probiotics
definition - transfer of stool from a healthy donor into the DI tract of an unhealthy individual suffering form C. dificile
method
husband's stool + normal saline
fecal matters are filtered
administered thru colonoscopy