Aug 14, 2024 05:19 PM
https://www.nature.com/articles/d41586-024-02601-4
INTRO: Johan Paulsson’s interest in antibiotics began with body aches and nausea in August 2021. His illness, which quickly progressed to a full-body bloodstream infection, landed him in the emergency department. “It was fairly dramatic,” recalls Paulsson. He spent a week in hospital and his organs began to fail. Although his memory of the time is fuzzy, he recalls that his physicians tried three different antibiotics, one by one, to find the drug that finally made him feel better.
Even in his delirium, Paulsson — a microbial biophysicist at Harvard Medical School in Boston, Massachusetts — was alarmed that the physicians couldn’t identify the microbe behind the mystery infection. They made some guesses and tested his blood for genes of likely suspects. But there was no test that could check for any and all bacteria. And some results didn’t come back until weeks after Paulsson had got better. Even so, the tests never confirmed exactly what had made him so sick.
Paulsson thought some of the tools he’d been developing to study microbes might help. The very day he left hospital, he got in touch with colleagues to plot a solution. The result was a US$104-million project with lofty goals: to better understand how bacteria evade medicines, to develop new antibiotic candidates and to diagnose infections and antimicrobial resistance efficiently and affordably. This project, called Defeating Antibiotic Resistance through Transformative Solutions (DARTS), was launched in 2023 and is one of the first big initiatives of the US Advanced Research Projects Agency for Health (ARPA-H).
Penicillin was discovered nearly a century ago, and it was followed by a bevy of antibiotics derived from soil microbes, particularly Actinomyces bacteria. For a time, these drugs were helping humans to win the fight against bacterial infections.
But the well soon started to run dry, as fewer and fewer compounds were discovered. At the same time, bacteria were becoming resistant to the medications in use. Today, most new antibiotics are simply variants of a known class and can be used for just a few years before resistance emerges — not only limiting the drugs’ efficacy, but also making their development a financial loser for pharmaceutical companies. “We have to run in order to stay in place,” says Kim Lewis, a microbiologist at Northeastern University in Boston.
Hongzhe Sun, a chemical biologist at the University of Hong Kong, says that in his part of the world, “we anticipate maybe the next pandemic will be the crisis of antibiotic resistance”. Indeed, a global crisis is already happening. According to a Lancet study, about 1.27 million deaths worldwide in 2019 could be attributed to drug-resistant infections, making them a leading cause of death1. By 2050, such infections could kill as many as ten million people every year2, according to an expert panel commissioned by the UK government in 2014.
Paulsson, Lewis, Sun and others seek to give humans back the edge in the antimicrobial arms race. Some scientists aim to expedite new antibiotics or to speed up the development of accessory molecules that help antibiotics work better, using artificial intelligence (AI) and other strategies. Others hope to slow down the development and spread of resistance on the microbe side.
Researchers are optimistic that a multipronged approach can help to turn the tide (see ‘Innovation gap’). Here, Nature profiles five of the strategies that scientists are pursuing. “We may be entering an era where we can discover new antibiotics faster than resistance can evolve,” says Jonathan Stokes, a micro-biologist at McMaster University in Hamilton, Canada... (MORE - details)
COVERED: Natural products ...... The promise of AI ...... Combination therapies ...... Immune assistance ...... Efficient diagnostics
INTRO: Johan Paulsson’s interest in antibiotics began with body aches and nausea in August 2021. His illness, which quickly progressed to a full-body bloodstream infection, landed him in the emergency department. “It was fairly dramatic,” recalls Paulsson. He spent a week in hospital and his organs began to fail. Although his memory of the time is fuzzy, he recalls that his physicians tried three different antibiotics, one by one, to find the drug that finally made him feel better.
Even in his delirium, Paulsson — a microbial biophysicist at Harvard Medical School in Boston, Massachusetts — was alarmed that the physicians couldn’t identify the microbe behind the mystery infection. They made some guesses and tested his blood for genes of likely suspects. But there was no test that could check for any and all bacteria. And some results didn’t come back until weeks after Paulsson had got better. Even so, the tests never confirmed exactly what had made him so sick.
Paulsson thought some of the tools he’d been developing to study microbes might help. The very day he left hospital, he got in touch with colleagues to plot a solution. The result was a US$104-million project with lofty goals: to better understand how bacteria evade medicines, to develop new antibiotic candidates and to diagnose infections and antimicrobial resistance efficiently and affordably. This project, called Defeating Antibiotic Resistance through Transformative Solutions (DARTS), was launched in 2023 and is one of the first big initiatives of the US Advanced Research Projects Agency for Health (ARPA-H).
Penicillin was discovered nearly a century ago, and it was followed by a bevy of antibiotics derived from soil microbes, particularly Actinomyces bacteria. For a time, these drugs were helping humans to win the fight against bacterial infections.
But the well soon started to run dry, as fewer and fewer compounds were discovered. At the same time, bacteria were becoming resistant to the medications in use. Today, most new antibiotics are simply variants of a known class and can be used for just a few years before resistance emerges — not only limiting the drugs’ efficacy, but also making their development a financial loser for pharmaceutical companies. “We have to run in order to stay in place,” says Kim Lewis, a microbiologist at Northeastern University in Boston.
Hongzhe Sun, a chemical biologist at the University of Hong Kong, says that in his part of the world, “we anticipate maybe the next pandemic will be the crisis of antibiotic resistance”. Indeed, a global crisis is already happening. According to a Lancet study, about 1.27 million deaths worldwide in 2019 could be attributed to drug-resistant infections, making them a leading cause of death1. By 2050, such infections could kill as many as ten million people every year2, according to an expert panel commissioned by the UK government in 2014.
Paulsson, Lewis, Sun and others seek to give humans back the edge in the antimicrobial arms race. Some scientists aim to expedite new antibiotics or to speed up the development of accessory molecules that help antibiotics work better, using artificial intelligence (AI) and other strategies. Others hope to slow down the development and spread of resistance on the microbe side.
Researchers are optimistic that a multipronged approach can help to turn the tide (see ‘Innovation gap’). Here, Nature profiles five of the strategies that scientists are pursuing. “We may be entering an era where we can discover new antibiotics faster than resistance can evolve,” says Jonathan Stokes, a micro-biologist at McMaster University in Hamilton, Canada... (MORE - details)
COVERED: Natural products ...... The promise of AI ...... Combination therapies ...... Immune assistance ...... Efficient diagnostics