US channels $104m into antimicrobial resistance project

The US government has set aside a $104 million pot of funding for research into bacterial behaviour and antibiotic resistance, in the hope of speeding up diagnosis and enabling the discovery of new drugs.

The project – organised as part of the Advanced Research Projects Agency for Health (ARPA-H) initiative set up last year by the Department of Health and Human Services (HHS) – will bring together 25 scientific teams from across the US, as well as the UK.

It will be led by Harvard Medical School systems biology expert Johan Paulsson and try to combine technologies like novel microscopy, microfluidics, single-cell assays, and machine learning into tools that can be used to identify bacteria and shine a light on their behaviour at the molecular level.

That, in turn, could reveal new targets for novel antibiotics, which are desperately needed in the face of rising levels of antimicrobial resistance (AMR), with some estimates suggesting that antibiotic-resistant bacteria have claimed more lives than COVID-19 in the last five years.

“What makes this novel is not that 25 research groups are funded to study antibiotic resistance, but that 25 groups with expertise in optics, mathematics, microbiology, and medicine can come together and do that as one coordinated team,” said Paulsson.

While a lot of attention has been focused on the dearth of new antibiotics coming through development – in part, a result of a near wholesale retreat from antibiotics R&D by the pharma industry – an early focus of the project will be tackling a bottleneck in diagnosis.

The teams will try to find better ways of identifying which pathogen is causing a bloodstream infection (sepsis) than the current, widely-used method of testing the patient’s blood for one or a few types of bacteria at a time, which can delay treatment.

Paulsson can draw on his own experience of this, after developing sepsis from an infection that he suspects originated from a tick on his dog.

The new diagnostic approach would rely on four main components, namely: improved microscopy to make bacterial imaging faster, cheaper, and more detailed; microfluidics to extract bacteria from blood; assays that can identify and genotype the pathogen from a single cell; and machine-learning tools to identify different bacteria from images.

Ultimately, the goal is to combine these factors into a single lab instrument, according to the researchers.

The second goal of new antibiotic development will be spearheaded by Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern University, and will focus on using the technologies to carry out high-throughput screening of potential drugs, alone and in combination.

In parallel, scientists in the consortium will deploy these techniques to try to work out why some bacteria – known as “persisters” – can survive antibiotic treatment.

The project is getting $70 million in federal funding upfront, and an additional $34 million if the first phase succeeds.