Scientists reverse bacterial resistance to antibiotics

antibiotics
Staphylococcus aureus - Antibiotics Test plate. Credit: CDC

The rise of antibiotic-resistant bacteria is a growing problem in the United States and the world. New findings by researchers in evolutionary biology and mathematics could help doctors better address the problem in a clinical setting.

Biologist Miriam Barlow of the University of California, Merced, and mathematician Kristina Crona of American University tested and found a way to return to a pre-resistant state. In research published in the open-access journal PLOS ONE, they show how to rewind the evolution of bacteria and verify treatment options for a family of 15 used to fight common infections, including penicillin.

Their work could have major implications for doctors attempting to keep patient infections at bay using "antibiotic cycling," in which a handful of different antibiotics are used on a rotating basis.

"Doctors don't take an ordered approach when they rotate antibiotics," Barlow said. "The doctors would benefit from a system of rotation that is proven. Our goal was to find a precise, ordered schedule of antibiotics that doctors could rely on and know that in the end, resistance will be reversed, and an antibiotic will work."

Dangers of Antibiotic Resistance

When bacteria grow powerful enough that antibiotics no longer work, it can be a matter of life and death. Recently, at the Ronald Reagan UCLA Medical Center, two people died and seven were injured when a medical scope used in patient procedures harbored drug-resistant bacteria. In the U.S. annually, more than 2 million people get infections that are resistant to antibiotics and at least 23,000 people die as a result, according to the Centers for Disease Control and Prevention.

Resistance to antibiotics is a natural part of the evolution of bacteria, and unavoidable given the many types of bacteria and the susceptibility of the human host. To compensate for bacterial evolution, a doctor fighting infections in an intensive care unit may reduce, rotate or discontinue different antibiotics to get them to be effective in the short term.

The researchers—from UC Merced, AU and UC Berkeley—have been leading the way to uncover how to reverse resistance in the drug environment. They've done so by combining lab work with mathematics and computer technology.

"We have learned so much about the human genome as well as the sequencing of bacteria," Crona said "Scientists now have lots and lots of data, but they need to make sense of it. Mathematics helps one to draw interpretations, find patterns and give insight into medical applications."

Challenging Work Yields Important Results

After creating bacteria in a lab, the researchers exposed them to 15 different antibiotics and measured their growth rates. From there, they computed the probability of mutations to return the bacteria to its harmless state using the aptly named "Time Machine" software.

Managing resistance in any drug environment is extremely difficult, because bacteria evolve so quickly, becoming highly resistant after many mutations. To find optimal cycling strategies, the researchers tested up to six drugs in rotation at a time and found optimal plans for reversing the evolution of .

"This shows antibiotics cycling works. As a medical application, physicians can take a more strategic approach," Crona said. "Uncovering optimal plans in antibiotics cycling presents a mathematical challenge. Mathematicians will need to create algorithms that can deliver optimal plans for a greater amount of antibiotics and bacteria."

The researchers hope to next test the treatment paths in a clinical setting, working with doctors to rotate antibiotics to maximize their efficacy.

"This work shows that there is still hope for antibiotics if we use them intelligently," Barlow said. "More research in this area and more research funding would make it possible to explore the options more comprehensively."


Explore further

Scientists must reduce antibiotic use in experiments

More information: PLOS ONE, dx.plos.org/10.1371/journal.pone.0122283
Journal information: PLoS ONE

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JVK
May 06, 2015
Journal article excerpt: "We have assumed that substitutions arise according to the strong selection weak mutation model (SSWM) [16] in which single substitutions reach fixation before the next substitution occurs."

After linking nutrient-dependent pheromone-controlled RNA-mediated amino acid substitutions to cell type differentiation and antibiotic resistance, they report their findings as if perturbed protein folding links the biophysically constrained chemistry of protein folding from mutations and natural selection to the evolution of antibiotic resistance.

This is what happens when generations of students who might otherwise become serious scientists are taught to believe in the pseudoscientific nonsense of neo-Darwinian theory.

See for comparison: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.n...24693353

JVK
May 06, 2015
"[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent.... Evolution was defined as "changes in gene frequencies in natural populations." The accumulation of genetic mutations was touted to be enough to change one species to another.... Assumptions, made but not verified, were taught as fact."

http://www.huffin...211.html

See also: http://www.scienc...4011.htm
"An enzyme called Soluble Lytic Transglycosylase (Slt) has been a suspect in recruiting beta lactamases to the struggle. Now it has been directly shown to cause the futile cycle of building and degrading new cell-wall material, creating the alarm signal the bacterium uses to start the production of beta-lactamases."

The seemingly futile cycles of thermodynamically-controlled protein biosynthesis and degradation are nutrient-dependent in species from microbes to humans.


JVK
May 06, 2015
Thermodynamic cycles of nutrient-dependent protein biosynthesis and degradation are perturbed by viruses. Viral microRNAs link perturbed protein folding to entropic elasticity. The anti-entropic epigenetic effects of nutrient-dependent microRNAs lead to amino acid substitutions via fine-tuning of the microRNA/messenger RNA balance.

In the absence of nutrient stress and/or social stress, DNA repair is linked to organism-level thermoregulation via the innate immune system. Organism-level thermoregulation is linked to successful reproduction via fixation of the nutrient-dependent amino acid substitutions.

Successful reproduction is linked to morphological and behavioral phenotypes via metabolic and genetic networks. The morphological and behavioral phenotypes are linked to nutrient-dependent pheromone-controlled biodiversity in this 5.5 minute-long presentation. https://www.youtu...youtu.be

JVK
May 06, 2015
Ecological variation leads to nutrient-dependent pheromone-controlled ecological adaptation in species from microbes to man via the conserved molecular epigenetics of cell type differentiation, which we detailed in our 1996 Hormones and Behavior review article: From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

Evolutionary theorists claim that ecological adaptation is due to mutations. It seems likely that most of them do not know the difference between a mutation and an amino acid substitution. In this report, Crona supposedly claims: "Mathematics helps one to draw interpretations, find patterns and give insight into medical applications."

If that were true, evolutionary theorists would by now have linked viral microRNAs and nutrient-dependent microRNAs to RNA-directed DNA methylation and cell type differentiation via amino acid substitutions and abandoned their ridiculous theories.

JVK
May 07, 2015
I reiterate: They assume "...that substitutions arise according to the strong selection weak mutation model (SSWM) [16] in which single substitutions reach fixation before the next substitution occurs."

See also: http://www.the-sc...ewiring/

Excerpt: "Bacteria that lack a vital protein for growing flagella—tail-like structures that enable the microbes to swim—can attain flagella in as little as four days..."

Given the speed at which they imply tjat selection for the "re-evolution" of the bacterial flagellum occurs, these theorists also appear to be creationists who have framed their results in the context of "evolved" proteins and a complex structure with a 4-day old function that enables nutrient-dependent pheromone-controlled reproduction.

For clarity, why don't they add details on the de novo creation of light-induced amino acids and the substitutions that differentiate all cell types in all genera?

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