How do bacteria actually become resistant to antibiotics?

• “What doesn’t kill me makes me stronger”, originally coined by Friedrich Nietzsche in 1888, is a perfect description of how bacteria develop antibiotic resistance.
• Contrary to a common belief, antibiotic resistance is not about your body becoming resistant to antibiotics.

How bacteria adapt

• The ability for bacteria to adapt lies in part with their astonishing rate of reproduction.
• While most changes are bad, sometimes they can help the bacteria grow in the presence of an antibiotic.
• This evolution of resistance can be seen by growing bacteria on a large agar plate (a nutrient support that bacteria like to grow on) with zones of increasing antibiotic levels.

They also exchange genetic material

• The other key mechanism enabling bacterial resistance is the exchange of genetic information between bacteria.
• In addition to the main chunk of DNA that encodes the bacterial genome, bacteria can host circular DNA snippets called plasmids.
• Plasmid exchange usually occurs by direct physical contact between bacteria.

4 ways bacteria resist

• Gram-positive bacteria like Staphylococcus aureus have a thick cell wall enclosing a lipid membrane.
• Antibiotics can hijack these entry routes, but bacteria can modify the cell wall, cell membrane and entry proteins to block antibiotic penetration.
• For example, bacteria increase the thickness of the cell wall to resist antibiotics like vancomycin.

• Bacteria have machinery known as efflux pumps, which regurgitate unwanted molecules from within the bacteria.
• Bacteria can alter the pump so it is more effective at removing the antibiotic, or they can simply make more pumps.
• Antibiotics, like most other drugs, generally work by blocking the function of important enzymes within the bacteria.
• If bacteria alter the target shape by changing the DNA/protein sequence, the antibiotic (key) can no longer bind to its target (lock).

Bacteria vs antibiotics

• While bacteria have developed mechanisms to resist antibiotics, these adaptations can come at a “fitness” cost.
• Bacteria may grow more slowly, or can be killed more easily by another antibiotic.
• This has led to the concept of “collateral sensitivity” to prevent or overcome resistance when treating patients, by using pairs of antibiotics.

Mark Blaskovich receives funding from a range of government, not-for-profit and commercial organisations for research into antibiotic discovery and development. He is affiliated with AAMRNet (Australian Antimicrobial Resistance Network), an organisation promoting improved care and development of antibiotics and antibiotic alternatives.