Class Notes (923,021)
CA (543,044)
UBC (12,806)
MICB (79)
MICB 201 (33)
Lecture 4

MICB 201 Lecture 4: Chapter 4 Notes

14 Pages
33 Views

Department
Microbiology
Course Code
MICB 201
Professor
Dave Oliver

This preview shows pages 1-3. Sign up to view the full 14 pages of the document.
Origin of ABs
Archaea don’t cause illnesses in humans information we have regarding
antibiotics only applies to bacteria
Deaths from infectious diseases has dramatically declined since 1900 b/c
improved sanitation, sewage treatment, medical care, decrease in poverty +
introduction of antibiotics
However, antibiotic-resistant bacteria spring up v fast after new AB
development
75% ABs today = naturally synthesized by soil microbes (esp. Members of
mycelial Actinobacteria)
Why do some bacteria synthesize ABs? reason unclear,
assumed to be for biological warfare but ABs only effective at
high concentrations unlikely to be reached in natural
environments
Semi-synthetic = natural ABs modified chemically, eg. β-lactam ABs
derived from penicillin
At clinically-relevant (high) concentrations, antibiotics work by:
disrupting cellular process/structure unique to target organism, or
Disrupting cellular process/structure in targets without affecting same
process in self
Eg. interfering w/ PG synthesis, translation, transcription,
replication + membrane damage
New PG synthesis and Effects of some ABs, eg. β-lactam
Bacterial cell must double all components in order to divide, including PG
Diff modes of cell division (specifically creation of new PG) for diff
bacteria eg. for unicellular Gm +ve bacteria:
Cocci
Division synthesis
New PG synthesized on either side of cell division
site
junction/ridge btwn new + old PG = wall band
Non-
spherical
Division + elongation synthesis
new PG added on either side of cell division site
new PG additionally synthesized at sites around
cell body (but not at ends), or only at ends
New PG added by breaking bonds in preexisting PG (by autolysins) then
adding disaccharide-peptide units to existing PG
Autolysins (periplasmic enzymes) catalyze breakage of
O-glycosidic bonds btwn NAM + NAG sugars, producing free end
to add new PG
Disaccharide-peptide unit = NAM-NAG disaccharide w/
pentapeptide
Made in cytoplasm/cytoplasmic membrane + transported
to periplasm
In periplasm, enzymes catalyze transglycosylation rxn
(O-glycosidic bond formation btwn NAM + NAG) and
transpeptidation rxn (peptide bond formation which leads
to release of 1 aa tetrapeptide)
Most clinically important ABs = β-lactams inhibit PG synthesis by binding to
enzyme that catalyzes transpeptidation, preventing transpeptidation rxn from
occurring
Many diff classes, eg. penicillins (penams), cephalosporins +
carbapenems, but all have same fxn and possess β-lactam ring
Vancomycin = inhibits PG synthesis by binding to AA4 and AA5 of pentapeptide
(if both are D-Ala), preventing both transpeptidation + transglycosylation
reactions
Can’t be used for Gm -ve b/c OM; diffuses v slowly across OM +
excluded by all porin channels
Polymyxin = one of few ABs which directly disrupts cellular structure (OM)
instead of inhibiting cellular process (eg. transpeptidation rxn)
Has polycationic ring (Full of NH3
+’s) interacts w/ negatively-charged
LPS core, displacing the Ca2+/Mg2+ ions and breaking down OM
After OM breakdown, polymyxin disrupts inner membrane by inserting its
hydrocarbon tail into membrane (detergent-like mechanism)
Only effective against Gm -ve for some reason
Chemical characteristics of ABs + Barriers to AB penetration
ABs = medium-sized chemicals (~100-1000 Daltons) in same category as
aas, nucleotides, sugars
Diff ABs = diff solubilities hydrophilic = chemicals v soluble in water,
hydrophobic = v not soluble in water
Correlated w/ relative amounts of polar/nonpolar content +
presence of charged groups
However, all ABs = high polar content + most are charged
Only the CM + OM are significant barriers to AB penetration capsular matrix,
S-layer pores + PG meshwork gaps = easy for ABs to pass thru
Although most ABs = v polar + charged, many are somehow able to
diffuse across CM freely
Some are passively/actively transported by CM permeases if
structurally similar to normal substrate, eg. Streptomycin
OM = less fluid + better barrier than CM, but allows ABs w/ high nonpolar
content to diffuse (eg. erythromycin + rifampin)
Some are transported into periplasm by porins β-lactams b/c
structurally similar to aa
Zwitterionic penams (eg. ampicillin + amoxicillin) penetrate
porins faster than anionic penams more effective ABs
Self-promoted uptake: some ABs “cross” OM by disrupting
structure, eg. polymyxin + streptomycin
An AB doesn’t either diffuse thru bilayer or travel thru porins; some can
take both routes depending on pH (affects ionization)
Factors contributing to a bacteria’s resistance to ABs:
Factor
How it helps with resistance
How to acquire
Can
antibiotic
pass thru
barriers?
Gm -ve or
Gm +ve
OM issues
Gm -ve generally more resistant
b/c OM; some ABs diffuse so slowly
basically useless
in Gm -ve, also consider ratio
of LPS vs. PL in OM, amount of
porin channels + size/selectivity
of porin channels
Can
antibiotic
bind?
Presence
+ suitability of
target sites
Bacteria will be resistant to ABs if
they lack the target sites of the ABs
eg. Mycoplasma sp. = no PG, so
resistant against β-lactam ABs
Vancomycin needs D-Ala @
AA4 + AA5
β-lactam ABs target
transpeptidase enzymes, but since
diff bacteria synthesize
transpeptidase enzymes w/ slightly
diff structures, variations exist btwn
bacterial resistance
Alteration to
target so AB can’t
bind
or replacement
with a different, but
functionally
equivalent,
molecule that AB
can’t bind to
Antibiotic-
modifying
enzymes
present?
Some bacteria can chemically
modify + inactivate ABs w/
enzymes
β-lactamases/Bla proteins
catalyze hydrolysis of β-lactam
rings
Chloroamphenicol transcetylase
(Cat) catalyzes acetylation of
chloramphenicol
Acquisition of
enzyme which
chemically modifies
+ deactivates AB
Antibiotic
efflux and/or
decreased
influx
Some bacteria have efflux protein
which transports AB out of cell
when it enters (specificity varies
btwn organisms)
Change in cell
envelope
composition that
decreases AB influx
Acquire new
efflux protein
Basically, acquired AB resistance (phenotype changes) comes from mutation
of existing genes or addition of new genes (genotype changes).

Loved by over 2.2 million students

Over 90% improved by at least one letter grade.

Leah — University of Toronto

OneClass has been such a huge help in my studies at UofT especially since I am a transfer student. OneClass is the study buddy I never had before and definitely gives me the extra push to get from a B to an A!

Leah — University of Toronto
Saarim — University of Michigan

Balancing social life With academics can be difficult, that is why I'm so glad that OneClass is out there where I can find the top notes for all of my classes. Now I can be the all-star student I want to be.

Saarim — University of Michigan
Jenna — University of Wisconsin

As a college student living on a college budget, I love how easy it is to earn gift cards just by submitting my notes.

Jenna — University of Wisconsin
Anne — University of California

OneClass has allowed me to catch up with my most difficult course! #lifesaver

Anne — University of California
Description
Origin of ABs Archaea dont cause illnesses in humans information we have regarding antibiotics only applies to bacteria Deaths from infectious diseases has dramatically declined since 1900 b/c improved sanitation, sewage treatment, medical care, decrease in poverty + introduction of antibiotics However, antibiotic-resistant bacteria spring up v fast after new AB development 75% ABs today = naturally synthesized by soil microbes (esp. Members of mycelial Actinobacteria) Why do some bacteria synthesize ABs? reason unclear, assumed to be for biological warfare but ABs only effective at high concentrations unlikely to be reached in natural environments Semi-synthetic = natural ABs modified chemically, eg. -lactam ABs derived from penicillin At clinically-relevant (high) concentrations, antibiotics work by: disrupting cellular process/structure unique to target organism, or Disrupting cellular process/structure in targets without affecting same process in self Eg. interfering w/ PG synthesis, translation, transcription, replication + membrane damage New PG synthesis and Effects of some ABs, eg. -lactam Bacterial cell must double all components in order to divide, including PG Diff modes of cell division (specifically creation of new PG) for diff bacteria eg. for unicellular Gm +ve bacteria: Cocci Division synthesis New PG synthesized on either side of cell division site junction/ridge btwn new + old PG = wall band Non- Division + elongation synthesis spherical new PG added on either side of cell division site new PG additionally synthesized at sites around cell body (but not at ends), or only at ends New PG added by breaking bonds in preexisting PG (by autolysins) then adding disaccharide-peptide units to existing PG Autolysins (periplasmic enzymes) catalyze breakage of O-glycosidic bonds btwn NAM + NAG sugars, producing free end to add new PG Disaccharide-peptide unit = NAM-NAG disaccharide w/ pentapeptide Made in cytoplasm/cytoplasmic membrane + transported to periplasm In periplasm, enzymes catalyze transglycosylation rxn (O-glycosidic bond formation btwn NAM + NAG) and transpeptidation rxn (peptide bond formation which leads to release of 1 aa tetrapeptide) Most clinically important ABs = -lactams inhibit PG synthesis by binding to enzyme that catalyzes transpeptidation, preventing transpeptidation rxn from occurring Many diff classes, eg. penicillins (penams), cephalosporins + carbapenems, but all have same fxn and possess -lactam ring Vancomycin = inhibits PG synthesis by binding to AA 4d AA o5pentapeptide (if both are D-Ala), preventing both transpeptidation + transglycosylation reactions Cant be used for Gm -ve b/c OM; diffuses v slowly across OM + excluded by all porin channels Polymyxin = one of few ABs which directly disrupts cellular structure (OM) instead of inhibiting cellular process (eg. transpeptidation rxn) Has polycationic ring (Full of NH s) interacts w/ negatively-charged 2+ 32+ LPS core, displacing the Ca /Mg ions and breaking down OM After OM breakdown, polymyxin disrupts inner membrane by inserting its hydrocarbon tail into membrane (detergent-like mechanism) Only effective against Gm -ve for some reason Chemical characteristics of ABs + Barriers to AB penetration ABs = medium-sized chemicals (~100-1000 Daltons) in same category as aas, nucleotides, sugars Diff ABs = diff solubilities hydrophilic = chemicals v soluble in water, hydrophobic = v not soluble in water Correlated w/ relative amounts of polar/nonpolar content + presence of charged groups However, all ABs = high polar content + most are charged Only the CM + OM are significant barriers to AB penetration capsular matrix, S-layer pores + PG meshwork gaps = easy for ABs to pass thru Although most ABs = v polar + charged, many are somehow able to diffuse across CM freely Some are passively/actively transported by CM permeases if structurally similar to normal substrate, eg. Streptomycin OM = less fluid + better barrier than CM, but allows ABs w/ high nonpolar content to diffuse (eg. erythromycin + rifampin) Some are transported into periplasm by porins -lactams b/c structurally similar to aa Zwitterionic penams (eg. ampicillin + amoxicillin) penetrate porins faster than anionic penams more effective ABs Self-promoted uptake: some ABs cross OM by disrupting structure, eg. polymyxin + streptomycin An AB doesnt either diffuse thru bilayer or travel thru porins; some can take both routes depending on pH (affects ionization) Factors contributing to a bacterias resistance to ABs: Factor How it helps with resistance How to acquire Can Gm -ve generally more resistant antibiotic b/c OM; some ABs diffuse so slowly pass thru basically useless barriers? in Gm -ve, also consider ratio Gm -ve or of LPS vs. PL in OM, amount of Gm +ve porin channels + size/selectivity OM issues of porin channels Can Bacteria will be resistant to ABs if Alteration to antibiotic they lack the target sites of the ABs target so AB cant bind? eg. Mycoplasma sp. = no PG, so bind Presence resistant against -lactam ABs or replacement + suitability of Vancomycin needs D-Ala @ with a different, but target sites AA4 + AA5 functionally -lactam ABs target equivalent, transpeptidase enzymes, but since molecule that AB diff bacteria synthesize cant bind to transpeptidase enzymes w/ slightly diff structures, variations exist btwn bacterial resistance Antibiotic- Some bacteria can chemically Acquisition of modifying modify + inactivate ABs w/ enzyme which enzymes enzymes chemically modifies present? -lactamases/Bla proteins + deactivates AB catalyze hydrolysis of -lactam rings Chloroamphenicol transcetylase (Cat) catalyzes acetylation of chloramphenicol Antibiotic Some bacteria have efflux protein Change in cell efflux and/or which transports AB out of cell envelope decreased when it enters (specificity varies composition that influx btwn organisms) decreases AB influx Acquire new efflux protein Basically, acquired AB resistance (phenotype changes) comes from mutation of existing genes or addition of new genes (genotype changes).
More Less
Unlock Document


Only pages 1-3 are available for preview. Some parts have been intentionally blurred.

Unlock Document
You're Reading a Preview

Unlock to view full version

Unlock Document

Log In


OR

Don't have an account?

Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


OR

By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.


Submit