Biology

Harvard scientists uncover an exploitable Achilles' heel common to most bacteria

Harvard scientists uncover an ...
In this artist's rendition of a bacterium, the blue dots represent the cell wall-building protein RodA – and disrupting that protein's function could be key to a new class of antibiotic
In this artist's rendition of a bacterium, the blue dots represent the cell wall-building protein RodA – and disrupting that protein's function could be key to a new class of antibiotic
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In this artist's rendition of a bacterium, the blue dots represent the cell wall-building protein RodA – and disrupting that protein's function could be key to a new class of antibiotic
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In this artist's rendition of a bacterium, the blue dots represent the cell wall-building protein RodA – and disrupting that protein's function could be key to a new class of antibiotic

Bacteria can be hardy little creatures, thanks mostly to their strong cell walls that can protect them against drugs, viruses and other dangers. Finding ways to disarm these defenses is a key component of antibiotics, and now researchers at Harvard Medical School have identified a structural weakness that seems to be built into a range of bacterial species, potentially paving the way for a new class of widely-effective antibacterial drugs.

The new study builds on previous research into a protein named RodA. While the protein itself has long been known, in 2016 the Harvard team was the first to discover that it builds the protective cell walls of bacteria out of sugar molecules and amino acids. Since RodA belongs to the SEDS family of proteins, which is common to almost all bacteria, the team realized it was the perfect target for a far-reaching antibiotic. And on closer examination of RodA, the researchers spotted a vulnerable looking cavity on the outer surface of the protein.

"What makes us excited is that this protein has a fairly discrete pocket that looks like it could be easily and effectively targeted with a drug that binds to it and interferes with the protein's ability to do its job," says David Rudner, co-senior author of the study.

To test whether this cavity was the Achilles' heel they were looking for, the scientists altered the structure of the protein in two species of bacteria, E. coli and Bacillus subtilis. These two were chosen because they're well understood and represent the two broad classes of disease-causing bacteria, gram-positive and gram-negative.

The team found that even small changes to the structure of the cavity caused the protein to malfunction, which in turn led the bacteria to swell up and burst. That suggests that a drug designed to trigger the same reaction would be an effective antibiotic.

"A chemical compound – an inhibitor – that binds to this pocket would interfere with the protein's ability to synthesize and maintain the bacterial wall," says Rudner. "That would, in essence, crack the wall, weaken the cell and set off a cascade that eventually causes it to die."

Better yet, because the SEDS family is so common, potential future drugs could be effective against a wide range of bacterial species.

"This highlights the beauty of super-basic scientific discovery," says Thomas Bernhardt, co-investigator on the study. "You get to the most fundamental level of things that are found across all species, and when something works in one of them, chances are it will work across the board."

The research was published in the journal Nature.

Source: Harvard Medical School

9 comments
michaelblock
Just what we need, another broad-spectrum antibiotic that decimates a large proportion of your protective gut biota
F. Tuijn
And when it is successful a modification will be made among the millions of bacterial species that are affected which will be transmitted to all others and make your antibiotic ineffective within a very short time. Brilliant.
BrianK56
What about the good bacteria? does it crack their cases also.
S Michael
MichaelBlock Your right on the money. There is always side effects and unintentional consequences. For God sake, think before you create these so-called drugs to help mankind.
Ralf Biernacki
Yes, drugs have side effects. We should stop using all of them, ever. Michael, you be the first.
CharlieSeattle
Hopefully the side effects will not act like a shotgun blast to good bacteria, like a class of insecticides called neonicotinoids have done to Beesm Butterflies and other insects. For more than a decade, the Environmental Protection Agency has been under pressure from environmentalists and beekeepers to reconsider its approval of a class of insecticides called neonicotinoids, based on a mounting body of research suggesting they harm bees and other pollinators at tiny doses. In a report released Wednesday, the EPA basically conceded the case.............20 years late!
asninsp
What is another essential protein had the same "pocket"?
MattII
F. Tuijn You may be correct, but the fear of being sent back to stage 1 shouldn't prevent us from at least attempting to get ahead.
b@man
Best way to attack these proteins is with electromagnetic waves, at the right frequency and stay away from drugs... and doctors, if you want to live:)