Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sandia Researchers Find Clues to Superbug Evolution

24.09.2014

Imagine going to the hospital with one disease and coming home with something much worse, or not coming home at all.

With the emergence and spread of antibiotic-resistance pathogens, healthcare-associated infections have become a serious threat. On any given day about one in 25 hospital patients has at least one such infection and as many as one in nine die as a result, according to the Centers for Disease Control and Prevention.


Dino Vournas, Sandia National Laboratories

Sandia National Laboratories’ researchers Kelly Williams, left, and Corey Hudson look at the mosaic pattern of one of the Klebsiella pneumoniae plasmids and discuss mechanisms that mobilize resistance genes.

Consider Klebsiella pneumoniae, not typically a ferocious pathogen, but now armed with resistance to virtually all antibiotics in current clinical use. It is the most common species of carbapenem-resistant Enterobacteriaceae (CRE) in the United States. As carbapenems are considered the antibiotic of last resort, CREs are a triple threat for their resistance to nearly all antibiotics, high mortality rates and ability to spread their resistance to other bacteria.

But there is hope. A team of Sandia National Laboratories microbiologists for the first time recently sequenced the entire genome of a Klebsiella pneumoniae strain, encoding New Delhi Metallo-beta-lactamase (NDM-1). They presented their findings in a paper published in PLOS One, “Resistance Determinants and Mobile Genetic Elements of an NDM-1 Encoding Klebsiella pneumoniae Strain.”

The Sandia team of Corey Hudson, Zach Bent, Robert Meagher and Kelly Williams is beginning to understand the bacteria’s multifaceted mechanisms for resistance. To do this, they developed several new bioinformatics tools for identifying mechanisms of genetic movement, tools that also might be effective at detecting bioengineering.

“Once we had the entire genome sequenced, it was a real eye opener to see the concentration of so many antibiotic resistant genes and so many different mechanisms for accumulating them,” explained Williams, a bioinformaticist. “Just sequencing this genome unlocked a vault of information about how genes move between bacteria and how DNA moves within the chromosome.”

Meagher first worked last year with Klebsiella pneumoniae ATCC BAA-2146 (Kpn2146), the first U.S. isolate found to encode NDM-1. Along with E.coli, it was used to test an automatic sequencing library preparation platform for the RapTOR Grand Challenge, a Sandia project that developed techniques to allow discovery of pathogens in clinical samples.

“I’ve been interested in multi-drug-resistant organisms for some time. The NDM-1 drug resistance trait is spreading rapidly worldwide, so there is a great need for diagnostic tools,” said Meagher. “This particular strain of Klebsiella pneumoniae is fascinating and terrifying because it’s resistant to practically everything. Some of that you can explain on the basis on NDM-1, but it’s also resistant to other classes of antibiotics that NDM-1 has no bearing on.”

Unlocking Klebsiella pneumoniae

Assembling an entire genome is like putting together a puzzle. Klebsiella pneumoniae turned out to have one large chromosome and four plasmids, small DNA molecules physically separate from and able to replicate independently of the bacterial cell’s chromosomal DNA. Plasmids often carry antibiotic resistant genes and other defense mechanisms.

The researchers discovered their Klebsiella pneumoniae bacteria encoded 34 separate enzymes of antibiotic resistance, as well as efflux pumps that move compounds out of cells, and mutations in chromosomal genes that are expected to confer resistance. They also identified several mechanisms that allow cells to mobilize resistance genes, both within a single cell and between cells.

“Each one of those genes has a story: how it got into this bacteria, where it has been, and how it has evolved,” said Williams.

Necessity leads to development of new tools

Klebsiella pneumoniae uses established mechanisms to move genes, such as “jumping genes” known as transposons, and genomic islands, mobile DNA elements that enable horizontal gene transfer between organisms. However, the organism has so many tricks and weapons that the research team had to go beyond existing bioinformatics tools and develop new ways of identifying mechanisms of genetic movement.

Williams and Hudson detected circular forms of transposons in movement, which has never been shown this way, and discovered sites within the genome undergoing homologous recombination, another gene mobilization mechanism. By applying two existing bioinformatics methods for detecting genomic islands, they found a third class of islands that neither method alone could have detected.

“To some extent, every extra piece of DNA that a bacteria acquires comes at some cost, so the bacteria doesn’t usually hang onto traits it doesn’t need,” said Hudson. “The further we dug down into the genome, the more stories we found about movement within the organism and from other organisms and the history of insults, like antibiotics, that it has faced. This particular bacteria is just getting nastier over time.”

Applying findings to future work

The findings are being applied to a Laboratory Directed Research and Development project led by Sandia microbiologist Eric Carnes, who is examining alternative approaches for treating drug-resistant organisms. “Instead of traditional antibiotics, we use a sequence-based approach to silence expression of drug-resistant genes,” said Meagher.

The researchers also are applying their understanding of Klebsiella pneumoniae’s mechanisms of resistance and their new bioinformatics tools to developing diagnostic tools to detect bioengineering. Looking across 10 related but distinct strains of Klebsiella pneumoniae, they pinpointed regions that were new to their strain, and so indicate genetic movement.

“By studying the pattern of movement, we can better characterize a natural genomic island,” said Hudson. “This leads down the path of what does an unnatural island look like, which is an indication of bioengineering. We hope to apply the knowledge we gained from sequencing Klebsiella pneumoniae to developing diagnostic tools that could detect bioengineering.”

Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corp., for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies and economic competitiveness.

Sandia news media contact: Patti Koning, pkoning@sandia.gov, (925) 294-4911

Patti Koning | newswise

More articles from Life Sciences:

nachricht Antibiotics: New substances break bacterial resistance
12.11.2019 | Martin-Luther-Universität Halle-Wittenberg

nachricht How the Zika virus can spread
11.11.2019 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

Im Focus: Distorted Atoms

In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.

An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...

Im Focus: A Memory Effect at Single-Atom Level

An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.

The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.

Im Focus: Shedding new light on the charging of lithium-ion batteries

Exposing cathodes to light decreases charge time by a factor of two in lithium-ion batteries.

Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...

Im Focus: Visible light and nanoparticle catalysts produce desirable bioactive molecules

Simple photochemical method takes advantage of quantum mechanics

Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

 
Latest News

How the Zika virus can spread

11.11.2019 | Life Sciences

Researchers find new potential approach to type 2 diabetes treatment

11.11.2019 | Health and Medicine

Medica 2019: Arteriosclerosis - new technologies help to find proper catheters and location of vasoconstriction

11.11.2019 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>