Posted tagged ‘antibiotic resistance’

New study observes Tuberculosis bacteria attacking antibiotics

June 8, 2018

Photograph by torange.biz

Tuberculosis was one of the deadliest known diseases, until antibiotics were discovered and used to dramatically reduce its incidence throughout the world. Unfortunately, before the infectious disease could be eradicated, drug-resistant forms emerged as a major public health threat — one quarter of the world’s population is currently infected with TB and 600,000 people develop drug-resistant TB annually.

New research at SLAC National Accelerator Laboratory is seeking to better understand how this antibiotic resistance develops, as recently reported in BMC Biology.

TB is caused by Mycobacterium tuberculosis bacteria, which attack the lungs and then spread to other parts of the body. The bacteria are transmitted to other people through the air, when an infected person speaks, coughs or sneezes.

These bacteria survive antimicrobial drugs by mutating. Their resilience is enhanced by the lengthy and complex nature of standard treatment, which requires patients to take four drugs every day for six to nine months. Patients often don’t complete this full course of TB treatment, causing the bacteria to evolve to survive the antibiotics.

Now, a team of international researchers has investigated an enzyme, called beta-lactamase, that is produced by the Mycobacterium tuberculosis bacteria. They wanted to understand the critical role this enzyme plays in TB drug resistance.

Specifically, the researchers made tiny crystals of beta-lactamase and mixed them with the antibiotic ceftriaxone. A fraction of a second later, they hit the enzyme-antibiotic mixture with ultrafast, intense X-ray pulses from SLAC’s Linac Coherent Light Source — taking millions of X-ray snapshots of the chemical reaction in real time for two seconds.

Putting these snapshots together, the researchers mapped out the 3D structure of the antibiotic as it interacted with the enzyme. They watched the bacterial enzyme bind to the antibiotic and then break open one of its key chemical bonds, making the antibiotic ineffective.

“For structural biologists, this is how we learn exactly how biology functions,” said Mark Hunter, PhD, staff scientist at SLAC and co-author on the study, in a recent news release. “We decipher a molecule’s structure at a certain point in time, and it gives us a better idea of how the molecule works.”

The research team plans to use their method to study additional antibiotics, observing in real time the rapid molecular processes that occur as the bacteria’s enzymes breakdown the drugs. Ultimately, they hope this knowledge can be used to design better antibiotics that can fight off these attacks.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Big bacteria may be easier to kill, new research suggests

March 21, 2018

Image by NIAID

The size of a cell is intrinsicThe size of a cell is intrinsically linked with its genetic makeup, growth rate and other fundamental properties. What would happen if scientists could control the size of pathogens?

That possibility isn’t completely outlandish: Stanford researchers have discovered a genetic “tuning knob” that can enlarge or shrink bacteria across a wide range — and this knob can be used to fatten up the bacteria to increase their susceptibility to certain antibiotics, as recently reported in Current Biology.

The research team is led by KC Huang, an associate professor of bioengineering and of microbiology and immunology at Stanford. Huang explained in a recent Stanford Engineering  news article:

“Most strategies to killing bacteria are linear: you find a very specific target and block it with a drug. These findings point in the direction of totally orthogonal therapies, in which you predispose cells to death by tweaking a global property like size.”

The researchers found that a single protein in E. coli, called MreB, acts as a master regulator of cell size by coordinating the construction of cell walls. So they manufactured many copies of the E. coli’s DNA, changing in each copy just one of the 347 letters in MreB’s genetic code. Using fluorescence-activated cell sorting, they then separated the individual cells with different sizes to create a library of cell-size mutants.

The team used this library to study how size impacts a cell’s physiology, including how bacterium grow and survive. For instance, they treated the various E. coli mutants with several antibiotics and found that larger E. coli were more sensitive to the drugs. A larger cell has more surface area and that increases the drug uptake, they said in the paper.

Huang said he hopes their techniques can be applied to other bacteria and used to help human health in the future. He added:

“While we don’t yet know how to twist this bacterial size dial in patients, it’s good to have such an exciting new therapeutic approach as antibiotic resistance becomes increasingly prevalent.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

 


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