Week 2: How do antibiotics work?

Introduction

In Week 1 you learned that antibiotics are used to treat bacterial infections. They either kill the bacteria outright or prevent them from growing and replicating. You were also introduced to the concept of ‘magic bullets’ – drugs such as antibiotics that are highly effective at treating infections without unduly harming the patient.

This second week of the course looks in more detail at how antibiotics work.

You will start by exploring how antibiotics can exert powerful antibacterial effects and yet be generally well tolerated by people and animals. You will then study the different modes of antibiotic action, looking in more detail in this week’s case study at the precise mechanism used by ß-lactam antibiotics. Finally, you will consider factors that determine antibiotic type, such as spectrum of activity and bactericidal or bacteriostatic nature.

Begin this week by watching the video below about the pioneering work of Paul Ehrlich (1854–1915). He discovered the first ‘magic bullet’ in 1909 – Salvarsan, a derivative of arsenic – which could cure syphilis. Ehrlich hoped that other ‘magic bullets’ which could be safely used to treat bacterial infections would swiftly follow. However, the world had to wait another ten years for penicillin to be accidentally discovered!

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Transcript: Video 1 In pursuit of ‘magic bullets’: the seminal work of Paul Ehrlich.

MICHAEL MOSLEY:

At the start of the 20th century, diseases you might have associated with mediaeval times were still rampant. Syphilis, for example. Now for centuries, doctors had used mercury to treat it. But being extremely toxic, it tended to kill the patients.

MAN 1:

Paul Ehrlich studied medicine in the early 1870s. But he spent an awful lot of time in the laboratory rather than the clinic, where he should have been.

MICHAEL MOSLEY:

One of the things Ehrlich was doing was playing around with artificial dyes. The first had been discovered in 1856. And soon, people went dye crazy.

His favourite colour was methylene blue. And with this, he made a remarkable discovery, one which would set him on the path to medical greatness.

MICHAEL MOSLEY:

When Ehrlich added a drop of methylene blue to tissue infected with bacteria, he noticed something astonishing-- only the bacteria was stained by the dye, not the tissue around them.

Now the fact that an artificial dye will selectively stain bacteria was remarkable. But it's what Ehrlich thought next that was truly revolutionary.

MAN 2:

What he did was he noted that some compounds were toxic. And he said, what if you create selective toxicity so that you can give somebody a compound that will kill off what's making them unwell and leave them unharmed. And he famously coined the phrase from a German folk story, you could create these magic bullets, which is what we've been trying to do ever since.

MICHAEL MOSLEY:

Initially, he tried finding a cure for sleeping sickness. But with the help of his Japanese assistant, Sahachiro Hata, he switched his attention to a pathogen that was rather more common in Germany. Common, but horribly disfiguring-- syphilis.

There were no cures. And the only treatment, mercury, made your hair and teeth fall out before eventually destroying your entire nervous system.

[MUSIC PLAYING]

Ehrlich hoped to find a magic bullet that would be more selective, poisoning the bacteria but not the rest of the body. Ehrlich thought that arsenic might be effective against syphilis. Arsenic is notoriously poisonous, but by this point, German chemists had made hundreds of different compounds of arsenic.

So Ehrlich asked his assistant, Hata to work his way systematically through them, hoping that amongst would be one that was safe and effective. Hata had found a way to infect rabbits with syphilis. He now set about the un-enviable task of testing arsenic compounds on them one after the other.

Some compounds killed both bacteria and rabbit. Some killed neither. Hata went through hundreds and hundreds of compounds, until, finally, he found one that was rather special.

Compound 606, it killed the bacteria, but, best of all, it left the dear old rabbit intact. This was the magic bullet they had been hoping for.

MAN 2:

Salvarsan 606 showed that Ehrlich was right. That these things were out there. All you have to do is methodically screen for them, and you would find them. It showed the power of methodically screening lots of compounds. 606-- 606 compounds to see what worked.

MAN 1:

The newspapers at the time carried it on the front pages. The medical profession were stunned.

MAN 2:

To be able to treat syphilis was miraculous, absolutely miraculous.

MICHAEL MOSLEY:

By the 1920s, Salvarsan was the world's most popular drug, particularly with men. But Ehrlich's hope that it would be just the first of many magic bullets proved ill founded. Infections caused by the most minor of injuries were still uncontrollable.

End transcript: Video 1 In pursuit of ‘magic bullets’: the seminal work of Paul Ehrlich.

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Video 1 In pursuit of ‘magic bullets’: the seminal work of Paul Ehrlich.

By the end of this week, you should be able to:

• recognise different types of commonly used antibiotics
• recall the characteristic features of bacterial and human or animal cells
• explain why antibiotics have selective toxicity
• demonstrate how commonly used antibiotics affect bacterial growth
• summarise the main mechanisms by which antibiotics stop infections from spreading and kill bacteria.