Scientists drill holes through deadly bacteria's Kevlar-like hide

Dec 05, 2008
Scientists drill holes through deadly bacteria's Kevlar-like hide
Seeing through walls. An experiment shows that when dividing strep bacteria are stripped of their surface proteins (left), they begin to grow back in just minutes. One surface protein, protein M (green), anchors to the spot where sortase A (red) assembles. Before the bacteria finish dividing (right), sortase A has already begun to migrate to the new site of division.

(PhysOrg.com) -- To protect themselves from human defenses, disease-causing bacteria have evolved a cell wall made from a nearly impenetrable tangle of tightly woven strands. That’s made it difficult for scientists to see what goes on inside these potentially deadly organisms. But that era is now over.

In research published in the Proceedings of the National Academy of Sciences, Rockefeller University researchers have figured out how to drill holes through the Kevlar-like hide of gram-positive bacteria without obliterating them, and in doing so, they’ve made it possible to study, from the inside out, most of the known bacteria on the planet.

The work, led by Vincent A. Fischetti, head of the Laboratory of Bacterial Pathogenesis and Immunology, provides, for the first time ever, a look inside the rapidly multiplying and highly contagious Streptococcus pyogenes, the culprit behind a myriad of diseases, including strep throat and rheumatic fever. At a time when organisms are increasingly acquiring “superbug” powers, Fischetti and his colleague Assaf Raz, a graduate student in the lab, have used the technique to look specifically at a well-known enzyme called sortase A and its distribution inside the cell. Common to all gram-positive bacteria, the enzyme functions by anchoring surface proteins to the cell wall, endowing the bacteria with their infectious properties.

“If you interfere with this process, you get naked bacteria and naked bacteria are unable to cause infection,” says Fischetti. “So the idea here is that the more we know how sortase functions inside the cell, the more strategies we’ll have to interfere with its activity stripping the bacteria of their pathogenic surface proteins.” Although the researchers worked with S. pyogenes, the approach could work on any gram-positive bacteria such as methicillin-resistant Staphylococcus aureus, or MRSA, which is increasingly becoming resistant to even our strongest antibiotics.

The technique relies on enzymes produced by viruses, called bacteriophages, which attack only bacteria. Unlike antibiotics, which take time to take effect, phage enzymes strike with blitzkrieg speed, preventing bacteria from mustering a defense. Usually, these enzymes destroy their target, leaving nothing but cellular debris behind. That’s because the pressure inside a bacterium is like a champagne bottle: Once it’s opened, it explodes. In their work, however, Fischetti and Raz figured out how to poke holes in S. pyogenes while keeping the bacteria intact. These holes provide an entryway for tags that fluoresce when they attach to molecules inside the altered bacteria, allowing scientists to visualize, from the inside out, what makes these single-celled powerhouses infectious.

In the past, if scientists wanted to study what goes on inside bacteria, they were largely limited to working with nonpathogenic types whose cell walls could be punctured with established methods. The new technique, however, allows them to directly study pathogenic bacteria and ask specific questions about them.

Fischetti and Raz were interested in whether the distribution of sortase A inside the cell affects the distribution of protein M, one of many surface proteins found on these bacteria. The researchers found that as the bacteria divide, the tagged sortase A assembles at a very specific location: the point of cell division where it anchors protein M. Interestingly, before the bacterium finishes dividing, sortase A starts to assemble at the new point of division — even before the recently formed bacteria starts dividing.

“So early assembly of sortase A at the division site allows bacteria to attach surface proteins to the cell wall as it is being built,” says Raz. “Whether or not sortase A is related to the division machinery we do not know yet, but we now have the tools to try and find out.”

Perhaps this migration is a way for bacteria to be ultra-organized. “Strep divide every 20 or 30 minutes under optimal conditions,” says Fischetti. “During that time, a lot of things are going on and the bug has to be extremely organized for all these things to happen very quickly. We now have the tools to start answering how these organisms carry out this feat. That’s one important thing that this work has accomplished. It could help us understand what makes this and other disease organisms function.”

Citation: Proceedings of the National Academy of Sciences 105 (47): 18549–18554 (November 25, 2008)

Provided by Rockefeller University

Explore further: 'Tiger heavyweight' Nepal hosts anti-poaching summit

add to favorites email to friend print save as pdf

Related Stories

Fresh supplies and experiments delivered to ISS

Jan 14, 2015

Yesterday, ESA astronaut Samantha Cristoforetti and NASA astronaut Butch Wilmore captured the Dragon spacecraft with its supplies and new experiments for the six astronauts living 400 km above our planet.

Mysteries of 'molecular machines' revealed

Dec 22, 2014

"Inside each cell in our bodies and inside every bacterium and virus are tiny but complex protein molecules that synthesize chemicals, replicate genetic material, turn each other on and off, and transport ...

Researchers discover protein protecting against chlorine

Dec 18, 2014

Chlorine is a common disinfectant that is used to kill bacteria, for example in swimming pools and drinking water supplies. Our immune system also produces chlorine, which causes proteins in bacteria to lose ...

Recommended for you

'Tiger heavyweight' Nepal hosts anti-poaching summit

12 hours ago

Nepal's success in turning tiger-fearing villagers into their protectors has seen none of the endangered cats killed for almost three years, offering key lessons for an anti-poaching summit opening in Kathmandu ...

GMO mosquito plan sparks outcry in Florida

Jan 31, 2015

A British company's plan to unleash hordes of genetically modified mosquitoes in Florida to reduce the threat of dengue fever and other diseases has sparked an outcry from fearful residents.

Population genomics unveil seahorse domain

Jan 30, 2015

In a finding vital to effective species management, a team including City College of New York biologists has determined that the lined seahorse (Hippocampus erectus) is more a permanent resident of the we ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.