“The basic idea is for an antimicrobial to target something in a bacteria that, in order to gain immunity, would require the bacteria to kill itself through a suicide mutation,” said Gerard Wong, a professor of materials science and engineering, of physics, and of bioengineering at the U. of I.
Wong is corresponding author of a paper accepted for publication in the Proceedings of the National Academy of Sciences. The paper is to be posted this week on the journal’s Web site.
The researchers show that a synthetic “hole punching” antimicrobial depends on the presence of phosphoethanolamine, a cone-shaped lipid found in high concentrations within Gram-negative bacterial membranes. Although PE lipids are commandeered to kill the bacteria, without the lipids the bacteria would die, also.
“It’s a Catch-22,” Wong said. “Some mutations bacteria can tolerate, and some mutations they cannot tolerate. In this case, the bacteria would have to go through a mutation that would kill it, in order to be immune to these antimicrobials.”
In their work, the researchers compared the survival of the bacterium Escherichia coli with that of a mutant strain of E. coli, which lacked PE lipids in its membrane. The fragile PE-deficient mutant strain out-survived the normal, healthy bacteria, when exposed to a “hole punching” synthetic antibiotic.
However, the opposite was true when both strains were exposed to tobramycin, a conventional metabolic antibiotic that targets the bacterial ribosomal machinery rather than the membrane.
The researchers first reported on compounds that functioned as molecular “hole punchers” last year in the Journal of the American Chemical Society. Their latest work further elucidates the “hole punching” mechanism.
“The antimicrobial re-organizes PE lipids into holes in the membrane,” said Wong, who also is a researcher at the university’s Beckman Institute. “The perforated membranes leak, and the bacteria die.”
Finding new ways to treat emerging pathogens that are more and more resistant to the best antibiotics will be increasingly important in the future, Wong said. “Now that we more fully understand how our molecular ‘hole punchers’ work, we can look for similar ways to make antimicrobials that bacteria cannot evolve immunity to.”
With Wong, the paper’s co-authors include U. of I. graduate student and lead author Lihua Yang, materials science and engineering professor Dallas R. Trinkle, microbiology professor John E. Cronan Jr., and University of Massachusetts polymer science and engineering professor Gregory N. Tew, a U. of I. alumnus.
The work was funded by the National Science Foundation, the National Institutes of Health and the Office of Naval Research.
James E. Kloeppel | University of Illinois
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences