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
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Physics and Astronomy
28.03.2017 | Health and Medicine
28.03.2017 | Life Sciences