Scientists Find a Weak Spot In Some Superbugs' Defenses

Researchers have found a new way to attack some of the bacteria behind treatment-resistant infections. An anonymous reader shares a report from Wired: In 2004, a 64-year-old woman in Indiana had a catheter put in to help with dialysis. Soon after the procedure, she came to a local hospital with low blood pressure and what turned out to be a dangerous antibiotic-resistant infection from a bacteria called Enterococcus faecalis. [...] After the patient in Indiana returned to the hospital, doctors sampled her blood and tested various antibiotics to see what might cure her infection. The strain she was infected with was already resistant to the antibiotic vancomycin, which was traditionally considered the treatment of last resort. But the bacteria that were making her sick were susceptible to a powerful new drug, approved by the FDA just a year before, called daptomycin. With a prescription for daptomycin, the patient improved enough to go home.

But two weeks later, the woman was back in the hospital again, this time with a high fever. Nothing her medical team tried worked, and the woman died. A study out today in the Proceedings of the National Academy of Sciences, though, offers new hope -- along with clues about how drug developers might fight back against this foe. VRE bacteria reproduce by pinching in at the center and dividing into two separate cells. Daptomycin fights VRE by binding to its cell membrane right at that center point, which disrupts its ability to divide, among other things. After the patient in Indiana died, doctors compared a sample of her blood with one they'd taken weeks earlier, when she first came to the hospital. They discovered that the daptomycin-resistant strain had a new mechanism that reorganized the cell. Daptomycin could no longer attach and halt the bacteria's cell division. "[The researchers] were puzzled that the cells somehow knew when to organize their membranes to resist the daptomycin," reports Wired. "[Researcher Ayesha Khan] noticed these drug-resistant strains had a lot of the protein LiaX both on the cell membranes and outside the cell, so she zeroed in on it. LiaX, the research team found, is an alarm system. The protein binds to daptomycin, sending a signal back telling the cell that it's time to reorganize. This same mechanism also helps VRE ward off the human immune system, they found, which might contribute to its deadly nature."

"We knew prior to this study that LiaX likely has a role in daptomycin resistance, and this work goes a long way toward explaining what that role is," Kelli Palmer, a biologist who studies antibiotic resistance at the University of Texas at Dallas, said. "It is critical that we understand how daptomycin resistance works at a molecular level, so that we can design strategies to reverse it."

Pretty amazing stuff

[110010001000]

What a great story.

I remember when

[rossdee]

A 'Superbug' was a VW beetle with a rounded (rather than flat) windscreen and a 1500cc motor

Re:

[grep -v '.*' *]

Don't forget it's washing-machine sounding motor. It's (was) distinctive. I once heard one coming and mentioned it to a friend of mine. "Really? How can you tell? Why look, you're right!"

Really? How can you NOT tell?

Re:

[_merlin]

The sound is caused by the uneven timing of the exhaust pulses on each cylinder bank being fed into a single manifold. Subaru 4-cylinder engines sound like that as well (with the exception of some performance models with extractors running between the cylinder banks so evenly-spaced exhaust pulses will reach the junction points.

What weak spot?

[scott_evil]

Right now, that LiaX mentioned is the reason why the bug is resistant to the best drug we've got. I wouldn't call it a weak spot until a vulnerability is found and exploited.

In other news, a weak spot has been found on the Challenger main battle tank. Its Chobham armour prevents penetration by both kinetic and explosive rounds. As soon as we work out how to bypass this armour, the tank will be rendered helpless.

Re: What weak spot?

[Way Smarter Than You]

I'd like a phased plasma rifle in the 40-watt range.

Re:

[BranMan]

"Hey, pal, just what you see"

BEHOLD!!!

[garyisabusyguy]

The power of cut and paste!

Whoever prepared this story left off the critical part of the tale, which is that they are now targeting the protein that causes the cell to reorganize thereby defeating the newest x-mycin on the market.

FTA:
A drug that could disrupt the signaling between LiaX and the cell, for example, won’t kill bacteria. But it will prevent the cell from knowing when to restructure its membrane, making it susceptible to daptomycin again.

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[account_deleted]

Comment removed based on user account deletion

Re:

[140Mandak262Jamuna]

Careful, you might get boobs or an Adams apple. Maybe both!

OR, one boob and several Adam's apples. They also use the same machine for gene therapy medicines ...

Re:

[Gilgaron]

Step one would be to make a monoclonal antibody to LiaX and see how the bugs react in vivo. If you're lucky, they don't cope and you just need a mab+antibiotic treatment cocktail. Otherwise you have to figure out the rest of the mechanism but knowing where to look is the trickiest part, so they're half way there already.

Re:

[backslashdot]

Identifying the molecule and its structure is 99.99999% of the work. After that you can engineer a specific binder (either small molecule or protein) for it a number of ways -- seriously you can can google that. They probably already have a list of LiaX inhibiting molecules. They would just need to test them and find out which ones can be made cheaply that also dont bind to other things (which cause side effects). It takes like 10 years to push it through FDA approval.

Re:

[phantomfive]

It shouldn't be too hard, womp proteins aren't much bigger than that and I used to bullseye them with a scalpel back home.

Re:

[bill_mcgonigle]

This woman died in a modern hospital filled to the brim with technological wonders.

You should be aware that if you statistically analyze the number of lives saved in hospitals with the number of medical errors, hospital-acquired infections, and drug interactions caused by hospitals, it's still about a wash in 2019. Many patients who stay at a hospital would have resolved at home without intervention.

Medicine will get better over time, but we're still in its adolescence.

Re:

[Gilgaron]

Where they came from isn't really relevant if you're septic, it is like worrying about which lamp caused the fire while your house is still ablaze. She was diabetic and had a catheter recently, so the pathogen likely got into her blood via those routes. A 64 year old diabetic dying of sepsis isn't going to be a candidate for exploratory surgery.

Re:

[Gilgaron]

If she was septic, opening her up would turn a blood infection (already a grave concern) into a full body cavity infection. She'd be dead in less than an hour.

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[Damian Harrison]

Sometimes it seems to me that people simply do not treat their health well. I have a favorite clinic in New York can visit their website [slashdot.org]. It isn't as big as some hospitals but it does medical tests very quickly and efficiently. If I feel bad, then I go there and check the blood. This doesn't give a 100% guarantee, but most often it shows what is wrong with me before I need urgent help.

Re:

[jeff4747]

When the infection is already in her blood, your approach isn't helpful. You need to fix the sepsis regardless of where it came from.

Let's pretend your lousy diagnosis is actually true, and that she somehow had a burst appendix that was causing her zero pain or other symptoms. You do surgery and repair the appendix....and she dies from sepsis anyway because fixing her appendix didn't fix the sepsis.

Re:

[jeff4747]

Repair the appendix? Um, what? You yank it out.

How terrible to not go into depth on the surgical procedure. :eyeroll:

First of all, you "fix" the sepsis by controlling the infection with antibiotics

And if you'd bother to read TFA, you'd find out that antibiotics were not effective. It's kinda the entire point of TFA.

But that didn't identify the source of FECAL bacteria in the blood.

Are you under the illusion that shit doesn't leave a person's body through a regular outlet?

No, of course not. It's utterly impossible for fecal bacteria to get anywhere outside the body!!! That's why nobody is supposed to wash their hands after taking a shit!!

And did you know that there's a condition that MIMICS acute appendicitis 100%

You mean, causing pain, swelling, tenderness and fever? S

Misuse

[xushi]

And when they become immune to that due to global incompetency and misuse, we are really fucked!