Antibiotic-resistant bacteria can share resources to cause chronic infections, Vanderbilt University investigators have discovered. Like the individual members of a gang who might be relatively harmless alone, they turn deadly when they get together with their “friends.”
The findings, reported Oct. 8 in Cell Host & Microbe, shed light on a long-standing question in infectious diseases and may inform new treatment strategies, said Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology.
One way that Staphylococcus aureus and other pathogens can become resistant to antibiotics is by changing the way they generate energy and becoming “small colony variants,” which are small and weak, Skaar explained.
“The question has been: how do bacteria that are less fit and grow poorly in the laboratory cause such persistent infections in humans?”
The current studies support the notion that antibiotic-resistant staph bacteria, including methicillin-resistant (MRSA) strains, can exchange nutrients with each other and even with other bacterial species, including the “normal” microbes of the microbiome, to increase their virulence during an infection.
The findings challenge infectious disease dogma, Skaar said.
“The thinking has been that if an infection becomes resistant to antibiotics, then the resistant organisms appeared clonally, meaning they’re all genetically the same.”
Skaar and his colleagues wondered if perhaps instead “there are a bunch of organisms that became resistant in different ways and that can exchange the molecules they’re each individually missing.”
Two fellows in the lab, Neal Hammer, Ph.D., and James Cassat, M.D., Ph.D., now an assistant professor of Pediatrics at Vanderbilt, tested this hypothesis by mixing together two different small colony variant strains of staph – one that can’t produce heme and the other that can’t make menaquinone. They found that in culture, these strains exchanged the two metabolites and grew as if they were wild-type staph.
Next, they tested the idea in a mouse model of bone infection (osteomyelitis). Antibiotic-resistant small colony variant S. aureus is the cause of chronic and difficult to treat osteomyelitis and also of lung infections in patients with cystic fibrosis (CF).
The investigators demonstrated that either staph strain alone (heme- or menaquinone-deficient) caused only minimal bone infection, but mixed together, they caused a fully virulent and bone-destroying infection.
“In bone, these bacteria are trading molecules,” Skaar said.
In collaboration with C. Buddy Creech, M.D., MPH, associate professor of Pediatrics, the researchers isolated samples of staph small colony variants and normal bacteria from the lungs of CF patients.
When individual CF staph small colony variants were mixed together in culture, they grew like wild-type bacteria. Likewise, co-culture of CF staph small colony variants with normal microbiome bacterial species also enhanced the growth of staph in culture.
“The microbiome of a cystic fibrosis patient’s lungs can provide nutrients to these small colony variants and revert them to wild-type behavior,” Skaar said.
“Our findings show that these antibiotic-resistant infections are not what we thought they were – they’re not a single strain of bacteria with a single lesion leading to the small colony variant phenotype,” he said. “Instead, they’re a mixed population of organisms that are sharing nutrients.
“They act like a big group of bullies until you hit them with drugs, then they stop sharing resources and are resistant. When the drugs go away, they start sharing resources again and get even tougher.
“We’re now a little bit smarter about how these organisms are behaving in an infection, which I think we can use to inform new treatment approaches.”
Preventing the nutrient exchange, for example, may offer a new therapeutic strategy against these antibiotic-resistant organisms, Skaar said.
This research was supported by grants from the National Institutes of Health (AI073843, AI069233, HD060554, AI113107).
Craig Boerner | newswise
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences