Researchers pick out new weapon to war the growing tide of antibiotic-resistant bacteria

Researchers pick out new weapon to war the growing tide of antibiotic-resistant bacteria


  • Post By : Kumar Jeetendra

  • Source: University of Colorado at Boulder

  • Date: 24 Dec,2020

As scientists around the globe wage war against a publication, deadly virus, one University of Colorado Boulder laboratory is working on new weapons to battle a distinct microbial threat: a rising tide of antibiotic-resistant bacteria which, if left unattended, could kill an estimated 10 million people annually by 2050.

In a paper published Friday in the journal PLOS Pathogens, Detweiler and her research team unveil their latest discovery–a chemical compound that works using a host’s innate immune response to push past cellular barriers that help bacteria resist antibiotics.

Together with their other recently released discoveries, the authors state, the finding could lead to a new arsenal for fighting what could be the next big public health threat.

If we don’t solve the problem of finding new antibiotics or somehow making old antibiotics work again, we are going to see sharply increasing deaths from bacterial infections we thought we had beaten decades ago. This study offers a totally new approach and could point the way toward new drugs that work better and have fewer side effects.”

Corrie Detweiler, Professor, University of Colorado Boulder

In the United States alone, 35,000 people die annually from bacterial infections that couldn’t be treated because they’ve grown immune to existing drugs. By 2050, the authors note, there could be many more deaths from antibiotic resistance than from cancer.

“As our present antibiotics work and adapt less, we risk essentially going back to a span 100 years ago, when even a minor infection could mean death,” said Detweiler.

The pandemic has shone even more light on the problem, she notes, as many individuals die not from the virus itself but from hard-to-treat secondary bacterial infections.

Meanwhile, other scholars worry that increased use of antibiotics to prevent or treat those secondary infections, while at times essential, may be exacerbating resistance.

Most antibiotics in use today were developed in the 1950s, and pharmaceutical firms have since scaled back on research in the field in favor of more profitable ventures.

To feed the pipeline, Detweiler’s laboratory developed a technique named SAFIRE for screening for new small molecules that work differently than older drugs.

Of 14,400 candidates screened from a library of existing chemicals, SAFIRE identified 70 that hold promise.

The new paper centers around”JD1,” that seems to be particularly good at infiltrating what are called”Gram-negative bacteria.”

With a tough exterior membrane that prevents antibiotics from accessing the mobile, and another inside membrane providing a buffer, these bacteria (like Salmonella and E. coli) are inherently tricky to treat.

But unlike other medications, JD1 takes advantage of the host’s first immune attack on that outer bacterial membrane, then slips inside and goes after the internal membrane too.

“This is the first study to show you could target a Gram-negative germs’s internal membrane by exploiting the innate immune response of the host,” Detweiler said.

In lab and rodent experiments, JD1 reduced survival and spread of Gram-negative bacteria called Salmonella enterica by 95%.

But while it damaged the bacterial cell membranes, it couldn’t penetrate the fine layer of cholesterol that lined its mammalian host’s cell membranes.

“Bacteria are vulnerable to JD1 in a manner that our cells are not,” said Detweiler, noting that for this reason, side-effects will probably be minimal.

Further studies are underway to research JD1 and other compounds like it.

Meanwhile, Detweiler has formed a spin-off company to help commercialize other chemicals that work by inhibiting pumps, known as”efflux pumps,” that bacteria use to pump out antibiotics.

“The reality is, evolution is way smarter than all the scientists put together and these germs will continue to evolve to resist what we throw at them,” she said. “We can’t rest on our laurels. We must keep feeding the pipeline.”

Journal reference:

Dombach, J.L., et al. (2020) A small molecule that mitigates bacterial infection disrupts Gram-negative cell membranes and is inhibited by cholesterol and neutral lipids. PLOS Pathogens.

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