01 October 2018
o effectively combat stubborn infections, drug developers need to better understand why bacteria are able to evade destruction with antibiotics. One team at the University of Copenhagen has discovered a surprising talent that some bacteria have that allows them to resist antibiotic attacks: hibernation. It's one of two recent discoveries that could spark new ideas for developing medicines to treat resistant infections.
The University of Copenhagen researchers discovered that some pathogenic bacteria enter a dormant state, much like hibernation, in the presence of antibiotics. When the antibiotics are gone, the bugs wake up and return to business as usual. The team published the finding in the journal Science Signaling.
The researchers started by studying E. coli samples from urinary tract infections that had initially responded to antibiotics.
“In time, the bacteria re-awoke and began to spread once again," said Kenn Gerdes, professor of biology at the University of Copenhagen, in a statement.
Gerdes’ team studied exactly what was happening in the cells that went dormant, and they found an enzyme that they believe put the bacteria in the hibernation-like state.
Separately, a team led by the University of Washington School of Medicine and the University of Nebraska Medical Center figured out another quirk some bacteria have that might also be able to be applied to drug development. Pseudomonas aeruginosa, which causes infections in the urinary tract and other sites, can be tricked into absorbing gallium, because the bacteria mistake the metal for nutritious food. The gallium disrupts the ability of the bacteria to multiply, the researchers reported in the journal Science Translational Medicine.
Gallium can fool bacteria because it looks much like iron, a nutrient that helps the bugs multiply and drive infection. "This and other essential processes require iron, and gallium is a monkey wrench that shuts the system down," said co-author Bradley Britigan, professor of internal medicine at the University of Nebraska Medical Center, in a statement.
They went on to test a single dose of gallium in mice and found that it cured lung infections caused by Pseudomonas aeruginosa. Bacteria can slowly develop resistance to bacteria, but when the researchers combined the metal with existing antibiotics, they found the potency of the attack increased.
They went on to test gallium in 20 people with cystic fibrosis, a disease marked by hard-to-fight lung infections. They reported that the dose tested was safe and that they saw an improvement in the patients’ lung function.
Disrupting the process by which bacteria obtain and use nutrients is not a new idea, but developing treatments to accomplish that feat has proven challenging. The authors noted in their study that their preliminary findings would need to be confirmed in a larger, placebo-controlled study, but that they’re encouraged by the prospect of using gallium to fight infections.
“Our proof-of-principle work with P. aeruginosa and the fact that gallium has broad-spectrum activity against many extracellular and intracellular pathogens raise the possibility that gallium or other iron-disrupting strategies may be useful in infections caused by a range of resistant organisms,” they wrote.
"The enzyme triggers a 'survival program' that almost all disease-causing bacteria deploy to survive in the wild and resist antibiotics in the body,” Gerdes said, adding that developing an antibiotic to target that mechanism could prove useful in fighting resistant infections.Print
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