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Comment – Precision Medicine to Beat Antibiotic Resistance

Antibiotics from engineered bacteria

Antibiotic droplets emitted from engineered bacteria (University of Warwick)

20 Jan. 2019. One of the scarier public health threats today is the emergence of bacteria resistant to antibiotics now in use. As we’ve documented numerous times in Science & Enterprise, the problem is global and growing, affecting millions of people just here in the U.S. and spreading among a growing number of infectious diseases.

A strategy often used to fight infections in a patient is to find an appropriate antibiotic for the responsible bacterium. But as bacteria mutate and evolve to become resistant to today’s drugs, we’re running out of antibiotics to battle those infections, with drug makers in a never-ending race to stay one step ahead.

A story we published on Friday describes a promising technology applied to the problem, suggesting an alternative approach. Our story tells about a group at Johns Hopkins University in Baltimore using a hand-held DNA sequencing device to identify vulnerabilities in the bacterial genome, which clinicians can then use to prescribe an appropriate antibiotic. The device is made by Oxford Nanopore Technologies in the U.K., a company we’ve also reported on before.

While it’s easy to focus on genomic sequencing hardware that you hold in one hand and connect to a laptop computer, don’t lose sight of the change in treatment strategy enabled by the technology. The Johns Hopkins team used the portable sequencer with patients’ blood samples, testing for Klebsiella pneumoniae bacteria , a microbe becoming resistant to many current antibiotics. The tests identified vulnerabilities in the bacterial genome, offering targets for antibiotics, with results that show the technique reduces the time needed to spot those targets.

This change in approach is another example of precision medicine, but with a twist. Much of what we today call precision medicine identifies the molecular composition of patients, such as cancer-causing genetic mutations, in order to find appropriate treatments addressing those mutations. In this case, precision is applied to the bacterial genome, to find vulnerabilities making the microbe more susceptible to antibiotics, with those targets used to identify appropriate drugs.

This change in diagnosing infections could lead to a precision-medicine approach for antibiotic discovery and development. We’re seeing signs that strategy may be feasible. In October 2018, we reported on a lab at University of Warwick in the U.K. that created a new antibiotic derived from soil microbes identified through bioinformatics, followed by genome editing with Crispr. The Warwick researchers acknowledge it took some trial and error to get their results, but they believe automation and robotics can make the process more efficient.

And finding new antibiotics from soil microbes is hardly a far-fetched idea. As we reported in June 2018, a team from University of California in Berkeley and Berkeley National Lab identified a wide range of new microorganisms in Northern California soil samples, many of which having genetic similarities to current antibiotics. Thus the soil under our feet may be a rich source of yet undiscovered new antibiotics.

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