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Antibiotic resistance: the coming plague?

What is an antibiotic?

Are all bacteria threats to human health?

How do antibiotics work?

How do bacteria become resistant?

How does antibiotic resistance spread?

What can be done?

Penicillin - the first documented antibiotic

Discovered by Alexander Fleming in 1929

Nobel Prize with Florey and Chain, 1945Penicillium mold kills Staphylococcus and

gram positive bacteria

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Penicillin is a beta-lactam that inhibits the formation of bacterial cell walls because it mimics the structure of cell wall components

penicillin

Bacterial peptidoglycan

“R” group can be modified to produce other antibiotics (methicillin, amoxicillin)

Streptomycin

isolated Streptomyces, soil bacterium

discovered by Selman Waksman in 1942

Nobel Prize in 1952

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Works by binding to bacterial ribosomes

Effective against gram-negative bacteria, including Tuberculosis

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Vancomycin - drug of last resort

(isolated from soil bacterium)

Glycopeptide that inhibits cell wall synthesis

Must be given intravenously

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Antibiotic sensitivity test

Bacteria from patient create a lawn across an agar plate

Each disk (black circles) contains a different antibiotic

Good medical practice involves culturing bacteria in patient samples

Microbes R us

Number of bacteria on our body surfaces is ~10x more than the number of cells in our bodies

Most inhabit GI tract where they synthesize some essential vitamins and amino acids and process otherwise indigestible foods

rDNA sequencing identifies over 70 species, including some unknown types

Human microbiota are complex

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Antibiotics select bacteria with genes that confer resistance

This doesn’t happen when the antibiotic isn’t there

MDR - TB

(Multi-drug resistant)

MRSA

(Methicillin-resistant)

Vancomycin-resistant

Antibiotic resistance increases due to:

New mutations (rare process)

Vertical transfer of DNA

Multiplication of existing resistant bacteria

Horizontal (lateral) transfer of DNA

Exchange of DNA between different bacteria

Antibiotic resistance can be transferred between different bacteria

Conjugation: a pilus sent out from one bacterium contacts a second bacterium, causing a pore to form

Bacteria are social! They live in complex communities (biofilms)

Bacteria sense the presence of other bacteria and produce molecules that clump them together

Plasmids can be passed from one bacterium to another through the pilus

Plasmids: small, circular pieces of DNA that replicate independently in bacterial cytoplasm

Both cells contain the plasmid after conjugation is complete

Transformation: Bacteria can pick up pieces of DNA from the environment

Inefficient process

BUT, you only need one to get many more!

Transformation is widely used in biotechnology

Plasmid genes encode proteins that confer resistance

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Vancomycin resistance

Vancomycin no longer binds to peptidoglycan

Antibiotic resistance can also spread in the environment

Partners in Health has pioneered new strategies for combating MDR-tuberculosis

Global inequities in health care produce acute situations in hospitals and prisons

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Abandon strategy based solely on institutionalization

Careful record keeping and detailed analyses of different TB strains

Home visits from health professionals to insure compliance with a complicated regimen of drugs

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Public health message