‘Knowing your enemy’ best advice in tackling infectious diseases

Bacteria are formidable enemies that deploy ingenious strategies for getting around our antibiotics, Dr Kathryn Holt of the University of Melbourne told the Schrodinger at 75 conference in Dublin.

The better we know this enemy, the more likely we are to save lives from infectious diseases. The key to more information comes from sequencing bacterial DNA, Dr Holt added. This approach had already revealed surprising ways that bacteria evolve resistance to our drugs.

“Several hospital outbreaks of drug resistant infections have now been traced to transmission of drug-resistant genes between different bacterial species, rather than the typical scenario where drug resistance strains spread between patients,” Holt said at the event hosted by Trinity College.

She outlined some of the ways bacteria swap resistance genes. “Some bacteria actively steal DNA from neighbouring cells. We recently learned that cholera harpoon neighbouring cells and reel in their DNA to try it on for size.” Others swap DNA in mobile plasmids, that can act like parasites, causing bacteria to build tunnels to other bacteria.

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Bacteria strains

Drug resistance genes were just a tiny fraction of the genes that move around between bacteria strains. This created a vast library of genetic diversity that bacteria can tap into.

“If you were to isolate a strain of E. coli from my gut and one from your gut, and compare their genomes, on average you find that they share little more than half their genes,” said Holt. Each strain will boast a few thousand genes that the other lacks. This only came to light in recent years, due to sharp falls in the cost of DNA sequencing, Holt explained.

“There is a vast gene pool available to the species. Much bigger than the number of genes we have in the human genome,” said Dr Holt, who called this the “pan-genome.” It was a surprise that microbes have so much genetic material on hand.

However, advances in technology are helping infectious disease scientists. Dr Holt pointed to the development of “third generation” DNA sequencing technology, which threads DNA through a tiny pore in a protein. This would be plugged into a laptop or phone to give real time DNA sequences. This will deliver huge gains for infectious disease management, said Dr Holt, revealing when and where new strains of microbes emerge.

“This could be taken into the jungle to sequence Zika or Ebola virus or into clinics or hospitals,” she said. “The resulting genomes can reveal a pathogen’s most intimate evolutionary secrets.”

Dr Holt predicted that in future such sequencing will become routine in medicine and public health.