Antimicrobial Resistance in Bacteria

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Antimicrobial Resistance in Bacteria

Antimicrobial Resistance

in Bacteria

By

Rungtip Chuanchuen

Department of Veterinary Public Health

Faculty of Veterinary Science, Chulalongkorn University


What to know

Selection pressure

Mechanisms of resistance

Gene transfer


Survival of the fittest

“Individuals having the highest level of

fitness for a particular environment tend

to survive longer in it.


Discovery of Penicillin

Ernest Duchesne

Alexander Fleming


Antimicrobials

Antibiotics

Biocides

Antiseptics

Disinfectants


Antimicrobial resistance

1. Intrinsic resistance

ex. Outer Membrane Impermeability

2. Acquired resistance

ex. mutation, acquire existing

resistance genes


Mechanisms of

resistance to antimicrobials

Drug inactivation

Target modification

Permeability alteration

Active efflux


Mechanisms of

resistance to antimicrobials

I. Drug inactivation or enzymatic inactivation

N-Acetyl

Glutamine

N-Actyl-

Muramic acid

-lactam

transpeptidase

-lactamase

D-ala

D-glu

2

3

Lys

D-ala

D-ala

1

transpeptidase


Mechanisms of

resistance to antimicrobials

II. Target modification

1)

Gyrase

2)

Supercoiled DNA

3)

Relaxed DNA

Fluoroquinolone

Mutant gyrase


Mechanisms of

resistance to antimicrobials

III. Permeability alteration

Changes of outer membrane barriers that limit the

antibiotic access to intracellular targets

Formation of biofilms

invasion

colonization

Formation


Mechanisms of

resistance to antimicrobials

IV. Active efflux

mechanisms that actively extrude drugs

out of cells

promote resistance to multiple drugs


Efflux Systems off –Low Level resistance

Enough intracellular drug to hit targets

outside

Drug

Cell wall

inside





Drug




= Drug targets


Efflux Systems On - High-Level Resistance

Not enough intracellular drug to hit targets

Drug

Drug

outside

Cell wall

inside

Efflux

Pump





Drug



= Drug targets


Antimicrobial cross resistance

Bacteria develop resistance to

one drug and elaborate

resistance to other drugs.


Biocide-antibiotic cross resistance

Biocides

Multidrug efflux systems are

off.

These bacteria are susceptible

to biocide and antibiotics.

Multidrug efflux systems are on.

The emergence of biocide -

resistant bacteria that are

simultaneously resistant to

multiple antibiotics


Transfer of resistance genes

Resistance genes

1. Plasmid

2. Chromosome

3. Transposon

4. Integrons


Transfer of resistance genes

1. Conjugation


Transfer of resistance genes

2. Transformation

donor

transformant

+

recipient


Transfer of resistance genes

3. Transduction


Transfer of resistance genes

4. Transposition


Selected examples of bacterial

resistance mechanisms

Transferable

resistance

Efflux Permeability Inactivation

Target

alteration

Ampicillin

Gentamycin

Erythromycin

Tetracycline

Enrofloxacin


Effects on human health

Direct effects

Resistance among zoonotic infection

Indirect effects

Resistance genes from bacteria in animals

are transferred to human pathogens

Gene flow


Effects on human health

Methicillin-resistance S. aureus

Penicillin-resistance S. pneumonia

Erythromycin-resistance S. pyogenes

Ampicillin-resistance Enterococcus

Vancomycin-resistance Enterococcus

Extended spectrum bata-lactamase (ESBL)

producing E. coli , K. pneumonia

Fluoroquinolone-resistance E. coli

Aminoglycoside-resistance Acinetobactor

baumanni & P. aeruginosa

Carbapenem-resistance A. baumanni

& P. aeruginosa


Resistance surveillance

Follow trend of drug resistance

Follow the emergence of drug resistance

Evaluate the efficiency of resistance

control program

Identify risk factor

Collect and comparison data from

different area

Promote the standard method for

the susceptibility test


Resistance surveillance

The major problem

do not have an active surveillance system

Data on antimicrobial resistance

Fragmentary

Biased

not systematic

not comparable


Movie time!!!!

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