Humanity’s fight against malicious bacteria continues, and each side is sharpening their proverbial blades and boosting their arsenal. The latest salvo was fired by the bacterial side: Antibiotic drug resistance is on the rise, and one urinary tract infection has been shown to be resistant to all of our antibiotics. Perhaps one day, infections that can be treated quite effortlessly today will once again become life-threatening.
Scientists are working around the clock to prevent the post-antibiotic age from arriving, and they’ve come up with some incredible new ways to break down bacterial defenses. The latest ammunition comes from a study published in the journal Cell Systems, which explains how bacterial envelopes – their biological shields – can be severely destabilized if a set number of genes relating to this function are knocked out.
The bacterial envelope is comprised of the inner cell membrane and the cell wall of each individual bacterium. Sometimes this includes a bacterial outer membrane, if it’s present. Overall, it provides structural integrity to the cell, and protects it from harmful chemicals or viral attack to varying degrees.
By successfully “knocking out,” or deleting, nearly 4,000 genes within the common bacteria E. coli, the stiffness and rigidity of its envelope bottomed out, leaving it open to chemical attack. The team then identified which of these knocked out genes were responsible for the envelope's destruction. If these results could be replicated across antibiotic-resistant bacteria, then the tide may turn in humanity’s favor once more.
“Until five or 10 years ago, we were never able to do this,” Douglas Weibel, a professor of biochemistry at the University of Wisconsin-Madison and coordinating researcher of the study, said in a statement. “The genetics, making a collection with every single gene knocked out, and then doing individual mechanical measurements on thousands of different mutants, would have been insane.”
E. coli, the bacteria used in the study. Fusebulb/Shutterstock
Previous studies have shown how Trojan horse-style attacks are possible on cells. DNA origami structures, usually containing anti-bacterial drugs (or in some cases chemotherapy drugs) are used to slip through gaps in the bacterial envelope or the cellular membrane of any other cell type; these structures then unfold, unleashing the drugs from within and killing the cell target from the inside.
This study opts for a different approach. The bacteria were placed in a gel that measured their envelope’s stiffness. Various genes were then knocked out – something that can be achieved by using an artificial piece of DNA to force out a targeted part of the genetic sequence – and the resulting effect, or lack thereof, on the stiffness of the envelope was examined.
Before this study, only one gene was known to play a role in cell mechanics in E. coli. Now, thanks to this study, we know that there are at least several dozen genes that directly impact envelope stiffness.