Study identifies key step in spread of drug resistance, opportunity for intervention
Spotless surfaces in hospitals can hide bacteria that rarely cause problems for healthy people but pose a serious threat to people with weakened immune systems. Acinetobacter baumannii causes life-threatening lung and bloodstream infections in hospitalized people. Such infections are among the most difficult to treat because these bacteria have evolved to withstand most antibiotics.
Now, researchers at Washington University School of Medicine in St. Louis have figured out a key step in the transmission of antibiotic resistance from one Acinetobacter bacterium to another, insight that sheds light on how antibiotic resistance spreads through a hospital or community.
The findings, published online Jan. 9 in Proceedings of the National Academy of Sciences, open up a new strategy to safeguard our ability to treat bacterial infections with antibiotics. The research indicates that the effectiveness of current antibiotics may be somewhat preserved by curtailing the spread of antibiotic-resistance genes.
“The problem of superbugs that are resistant to all antibiotics is bigger than just Acinetobacter,” said senior author Mario Feldman, associate professor of molecular microbiology. “What are we going to do when antibiotics don’t work anymore? We can look for new antibiotics, but bacteria will always find a way to develop resistance again. We have to stop resistance from spreading, too.”
Acinetobacter strains carry the genetic blueprints for drug resistance on small loops of DNA called plasmids that come in two sizes. Big plasmids, which are prone to accumulating ever more antibiotic-resistance genes, carry the genetic instructions to build a needle-like appendage to insert copies of themselves into nearby bacteria. Small plasmids, which contain resistance genes against a single but important group of antibiotics known as carbapenems, lack their own distribution tools so they invade new bacteria by tagging along with the large plasmids.
“Plasmids want to take over the world,” Feldman said. “Plasmids are selfish genetic elements that just want to procreate as much as possible, and they co-opt bacteria to do that. That is scary for us because the plasmids are very efficient at collecting antibiotic resistance. So as they reproduce and infect more bacteria, they spread drug resistance.”
The plasmids’ reproductive strategy requires close contact between two bacteria. But that raises a question: How do two bacteria ever get near enough to transmit plasmids to each other? Most Acinetobacter guard against strangers with a system that injects lethal proteins into any unrelated bacteria that approach too closely, thus reducing the changes of spreading antibiotic-resistance genes.
Feldman, along with first author and postdoctoral fellow Gisela Di Venanzio and colleagues, mutated the plasmids to find out how they get around such bacterial defenses. Their work was supported in part by Washington University’s Faculty Diversity Scholars Program, which encourages recruitment of underrepresented minority scientists. Feldman and Di Venanzio are both from Argentina.
The researchers found that plasmids disable bacteria’s self-defense systems so that plasmids can inject copies of themselves into neighboring bacteria, conferring drug resistance on the unwitting bacterial neighbors. By forcing the bacteria in which they reside to lay down their weapons, the plasmid ensures that nearby bacteria aren’t killed before the plasmids can infect them. The researchers found that mutating plasmids so they could not interfere with the bacteria’s defenses – or mutating the bacteria so the defenses could not be lowered – prevented plasmids from spreading.
These findings provide a novel opening to interrupt the spread of drug resistance, the researchers said. The genes involved have been identified. Now researchers have to find compounds that prevent plasmids from disrupting bacterial-defense systems.
“If we found an inhibitor, we could clean hospital surfaces with it and prevent the dissemination of drug resistance,” Feldman said. “This is an out-of-the-box idea, but it’s what we need. If we just find new antibiotics, the bacteria will just become resistant again. We need to find therapies that don’t kill the bacteria but prevent it from becoming drug-resistant, so we can continue using our antibiotics into the future.”
The Latest on: Antibiotic resistance
via Google News
The Latest on: Antibiotic resistance
- How a new antibiotic destroys extremely drug-resistant tuberculosison August 16, 2019 at 6:25 am
The Food and Drug Administration on Wednesday approved a new antibiotic that, when combined with two existing antibiotics, can tackle the most formidable and deadly forms of tuberculosis.
- Antibiotic Resistance Thwarted with Biosurfactanton August 16, 2019 at 5:13 am
Pseudomonas aeruginosa-produced rhamnolipids target the plasma membrane of Staphylococcus aureus (labeled here in red) to increase permeability to aminoglycoside antibiotics. [Conlon Lab, UNC School ...
- Development of a nebramine-cyclam conjugate as an antibacterial adjuvant to potentiate β-lactam antibiotics against multidrug-resistant P. aeruginosaon August 15, 2019 at 10:32 pm
All prices are NET prices. VAT will be added later in the checkout. Zgurskaya HI, Lopez CA, Gnanakaran S. Permeability barrier of gram-negative cell envelopes and approaches to bypass it. ACS Infect ...
- FDA Finds Unexpected Antibiotic Resistance Genes in ‘Gene-Edited’ Dehorned Cattleon August 15, 2019 at 11:04 am
Gene-editing is seen by many as the ultimate in precision breeding. Polled cattle, whose horns have been genetically removed, have been presented as exemplars of this — a socially beneficial use of ...
- Scientists find powerful potential weapon to overcome antibiotic resistanceon August 15, 2019 at 10:35 am
Staphylococcus aureus bacteria are a major cause of serious infections that often persist despite antibiotic treatment, but scientists at the UNC School of Medicine have now discovered a way to ...
- Scientists find a potent weapon against antibiotic resistanceon August 15, 2019 at 7:44 am
Antibiotic resistance is a big threat to global health, and a growing number of infections are now becoming harder to treat. Now, a team of researchers may have found a potent weapon against ...
- FDA approves new antibiotic for drug-resistant tuberculosison August 14, 2019 at 2:51 pm
Aug. 14 (UPI) --The U.S. Food and Drug Administration approved a new antibiotic for highly drug-resistant tuberculosis. The agency approved the use of pretomanid tablets, developed by global nonprofit ...
- New antibiotic approved for drug-resistant tuberculosison August 14, 2019 at 11:27 am
The Food and Drug Administration on Wednesday approved a new drug for highly drug-resistant tuberculosis, the world’s leading infectious cause of death. Tuberculosis kills 1.6 million people a year, ...
- Antibiotics for UTIs: Recipe for Resistance Down the Road?on August 13, 2019 at 4:21 pm
British patients diagnosed with urinary tract infections (UTIs) rarely had any testing performed before receiving antibiotics, a records analysis indicated. Almost 86% of patients received antibiotics ...
- Bogotá River anthropogenic contamination alters microbial communities and promotes spread of antibiotic resistance geneson August 13, 2019 at 2:30 am
The increase in antibiotic resistant bacteria has raised global concern regarding the future effectiveness of antibiotics. Human activities that influence microbial communities and environmental ...
via Bing News