Scientists reengineer antibiotic to overcome dangerous antibiotic-resistant bacteria

Scientists reengineer antibiotic to overcome dangerous antibiotic-resistant bacteria.

ScienceDaily (Aug. 25, 2011) — A team of scientists from The Scripps Research Institute has successfully reengineered an important antibiotic to kill the deadliest antibiotic-resistant bacteria. The compound could one day be used clinically to treat patients with life-threatening and highly resistant bacterial infections.

The results were published in an advanced online issue of the Journal of the American Chemical Society.

“[These results] have true clinical significance and chart a path forward for the development of next generation antibiotics for the treatment of the most serious resistant bacterial infections,” said Dale L. Boger, who is Richard and Alice Cramer Professor of Chemistry at The Scripps Research Institute and senior author of the new study. “The result could not be predicted. It really required the preparation of the molecule and the establishment of its properties.”

The compound synthesized is an analogue of the well-known commercial antibiotic vancomycin.

The new analogue was prepared in an elegant total synthesis, a momentous achievement from a synthetic chemistry point of view. “In addition to the elegantly designed synthesis,” said Jian Xie, postdoctoral fellow in Boger’s group and first author on the publication, “I am exceedingly gratified that our results could have the potential to be a great service to mankind.”

A Single Atom Changes Everything

Vancomycin is an antibiotic of last resort, which is used only after treatment with other antibiotics has failed. Clinically, it is used to treat patients that are either infected with the virulent methicillin-resistant Staphylococcus aureus (MRSA), individuals on dialysis, or those allergic to beta-lactam antibiotics (penicillin, cephalosporins).

The drug was first used clinically in the 1950s, and the first vancomycin-resistant bacterial strains were isolated in the 1980s.

Vancomycin normally works by grabbing hold of and sequestering the bacterial cell-wall making machinery, a peptidoglycan (carbohydrate and peptide containing molecule). Only Gram-positive bacteria have a cell wall, which is a membrane on the cell’s outer surface.

The antibiotic binds so tightly to the peptidoglycan that the bacteria can no longer use the machinery to make their cell wall and thus die.

Unfortunately, bacteria have found a way to alter the peptidoglycan in such a way that the antibiotic can no longer grab hold. Think of it as trying to hold a ball without any fingers. Biochemically the bacteria express a mutant form of the peptidoglycan in which properties of a key atom used in the recognition process are changed. This simply means where there once was something attractive there is now something repulsive. Chemically, the bacteria replace an amide (carbonyl, RC=O linked to an amine) with an ester (a carbonyl, RC=O linked to an oxygen, O).

This one atom change changes the entire game and renders vancomycin ineffective. Until now.

Reengineering Vancomycin

Like magnets, molecular interactions can be attractive (oppositely charged) or repulsive (identically charged). What chemists in the Boger lab have done is made this key interaction no longer repulsive, but attractive.

So now the new vancomycin analogue can grab hold of the mutant peptidoglycan, and again prevent the bacteria from making the cell wall and killing the resistant bacteria. But what is so remarkable about the design is that the redesigned antibiotic maintains its ability to bind the wild type peptidoglycan as well.

Changing the properties of a key amide at the core of the natural products structure required a new synthetic strategy that only the most talented chemists could achieve in the lab. The preparation of the entire structure took a great deal of time and a fresh approach.

The new compound has an amidine (an iminium, RC=NH+ linked to a nitrogen, N) instead of an amide at a key position buried in the interior of the natural product. However, to install such a functional group, the chemical properties of the amide carbonyl were not useful, as the natural product has seven of them.

Instead, the group relied on the chemical properties of sulfur (S), oxygen’s downstairs neighbor in the periodic table, to install the desired nitrogen. To do this, a second analogue was prepared in which the key amide was chemically altered to a thioamide. “The thioamide allowed us to make any modification at the residue 4 amide that we would like to make, such as the amidine, but we could also make the methylene analogue,” said Boger citing work published in another paper (B. Crowley and D. L. Boger, J. Am. Chem. Soc. 128: 2885-2892). “And there are other modifications that we are making at the present time that we haven’t disclosed. We are just getting to that work.”

The most fundamental finding in the synthesis was that the installation of the amidine could be done in the last step, as a single-step conversion, on the fully unprotected thioamide analogue. Providing an elegant and novel approach to the analogue, which contrasts other published multistep procedures. This chemical behavior was, as Boger said, “an astonishing result as there are no protecting groups and it is a single step reaction… in the end it was the simplest and most straightforward way to prepare the amidine.”

Although it is still at its early stages and there is much work ahead. Currently, the only route known to make the new antibiotic is the one published by Boger and his co-workers, which presently provides laboratory amounts of the compound. So Professor Boger now looks forward and will continue to investigate the “host of alternative approaches” for the preparation of the molecule “such as reengineered organisms to produce the material or semi-synthetic approaches to the analogue. That is going to be part of the next stage of the work.”

In addition to Boger and Xie, other contributors to the paper include Joshua G. Pierce, Robert C. James, and Akinori Okano.

The work was funded by the U.S. National Institute of Health (CA041101) and the Skaggs Institute for Chemical Biology.

Journal Reference:

  1. Jian Xie, Joshua G. Pierce, Robert C. James, Akinori Okano, Dale L. Boger. A Redesigned Vancomycin Engineered for Duald-Ala-d-Ala andd-Ala-d-Lac Binding Exhibits Potent Antimicrobial Activity Against Vancomycin-Resistant Bacteria. Journal of the American Chemical Society, 2011; 110816100911095 DOI: 10.1021/ja207142h

The Shape of the Global Economy Will Fundamentally Change

The Shape of the Global Economy Will Fundamentally Change – By Mohamed El-Erian | Foreign Policy.

Who would have thought just 18 months ago that a member of the eurozone, the most elite club of economies in Europe, could have a worse credit rating than Pakistan? And yet this is the case for Greece today, perched on the verge of a debt restructuring; two other eurozone countries (Ireland and Portugal), meanwhile, are already in Europe’s intensive care unit, receiving large bailouts.

And who would have thought that a rating agency would dare question the sacred AAA credit rating of the United States, the sole supplier of global public goods such as the international reserve currency (the dollar) and a financial system that serves as the nexus of international capital flow? Still, that’s exactly what Standard & Poor’s has done: In August the agency downgraded the United States’ AAA status to AA+, citing policymaking uncertainty in Washington and the country’s lack of a long-term plan to deal with its fiscal problems.

And who would have thought that the same country, which is renowned for its flexible labor markets and dynamic entrepreneurship, would experience a persistently high unemployment rate? Well, this is the case for the United States, where unemployment is stuck at around 9 percent, unemployment among 20-to-24-year-olds is a staggering 14.5 percent, and the related joblessness problems are becoming increasingly structural in nature.

There are, of course, several bespoke reasons for these developments. But together, they speak to major realignments that are fundamentally changing the character of the global economy and how it functions. Three things in particular have had a significant influence, and they will continue to shape the world we live in for years to come.

First, too many advanced economies face problems rooted far below the surface, in their balance sheets and in the structure of their economies. This is not just about the unemployment crisis and the rapidly deteriorating public finances that, in cases such as Greece’s, have reached alarming levels. It is also about malfunctioning housing markets, a continued breakdown in bank credit intermediation, and weak political leadership in the midst of messy party politics.

Second, rather than deal with these structural problems, policymakers have preferred to kick the can down the road. As a result, the problems have festered and become more entrenched, and the risk of adverse contagion has risen.

This is most obvious in Europe, where a liquidity approach — involving piling new debt on top of already crushing obligations — has repeatedly been applied to Greece’s debt solvency crisis. This has also transferred massive liabilities from the private sector to Greek and European taxpayers and contaminated previously healthy institutions such as the European Central Bank. It is also the case in the United States, where unprecedented stimulus spending has failed to sufficiently reignite growth and job creation.

Third, several emerging economies have hit their developmental breakout phase, largely undeterred until now by the misfortunes of the developed world. You see this in Brazil, China, Indonesia, and several other countries. In the process, they have gone from strength to strength, so much so that their economies have started overheating at a time when more established countries are languishing. This is new territory for the global marketplace, one in which the less mature countries are more robust and resilient than their advanced peers and are able to grow sustainably at high levels while also strengthening their balance sheets.

Absent a major policy mistake — a lurch toward protectionism, disorderly defaults, or disruptions to the international payment and settlement system, for instance — we should expect these global realignments to continue.

It will take several years for the advanced economies to fully rehabilitate their balance sheets and restore the conditions for high growth and employment creation. In the meantime, income and wealth distribution will become even more skewed, morphing from an economic issue into a sociopolitical one.

The combination of stretched balance sheets and disappointingly slow growth also means that the advanced countries will opt for a mix of approaches to deal with recurrent debt concerns as they continue to de-lever from the age of credit and debt-entitlement. Some, such as Britain, will rely primarily on years of budgetary austerity. Others, like Greece, will succumb to debt restructuring.

Then there is the United States, the economy that anchors the core of the global economic and financial systems. It will initially opt for financial repression — essentially a hidden taxation of creditors and depositors — and attempt higher inflation to address its balance sheet issues. With time, however, it will likely be forced into greater austerity amid noisy political posturing and bickering.

The messier this transition, the greater the risk of undermining the international standing of America’s global public goods. This in turn will challenge a global monetary system built on the assumption that its core — the United States — remains economically strong.

This is an important qualifier for what otherwise would be a far more encouraging outlook for much, though not all, of the emerging world. Look for these countries to continue to close the income and wealth gaps vis-à-vis the advanced countries. In the process, they will pull millions more out of poverty, providing them with greater economic opportunities and better access to education, health care, and nutrition.

As they continue to grow, emerging countries will push for greater accommodation on the part of a global economy that is still overdominated by the advanced economies. Global governance issues will come to the fore. International institutions will be pressured to reform more seriously. And multilateral negotiations will need to be more respectful of the growing strength of the emerging countries.

All this translates into an unusually fluid global economy — and a world in which many established parameters will instead become variables. The sooner we prepare for it, the greater the chance that we are beneficiaries of the transformations taking place, not their victims.

Roadwork Can Spread Invasive Species

Roadwork Can Spread Invasive Species: Scientific American Podcast.

Invasive species get a bad rap—but we humans are usually to blame for their spread. Take Japanese stiltgrass, an invasive that arrived from Asia nearly 100 years ago as a packing material for porcelain. When it creeps into forests, it forms dense carpets that can choke out native tree seedlings. And in the last 15 years, the grass has infested rural roads throughout Pennsylvania’s Rothrock State Forest—much faster than foresters expected.

Researchers thought the cause could be another human activity—road maintenance. They spray-painted 320,000 dead safflower seeds, and placed them along state forest roads. After routine road grading, they combed through the gravel to recover them. And they found that some seeds had been carried hundreds of feet down the road. Much farther than the few feet seeds can travel on their own—perhaps explaining the grass’ rapid spread.

They presented those results at a meeting of the Ecological Society of America. [Emily Rauschert and David Mortensen, Human-mediated spread of invasive plants across a landscape]

Still, roads need to be safe for drivers. So the researchers propose smoothing shorter segments at a time, or doing it less frequently. Because where humans go, invasives often follow—whether by sea or on land.

—Christopher Intagliata

Mysteries of ozone depletion continue 25 years after the discovery of the Antarctic ozone hole

Mysteries of ozone depletion continue 25 years after the discovery of the Antarctic ozone hole.

ScienceDaily (Aug. 29, 2011) — Even after many decades of studying ozone and its loss from our atmosphere miles above Earth, plenty of mysteries and surprises remain, including an unexpected loss of ozone over the Arctic this past winter, an authority on the topic said in Denver Colorado on May 29. She also discussed chemistry and climate change, including some proposed ideas to “geoengineer” Earth’s climate to slow down or reverse global warming.

The talk happened at the 242nd National Meeting & Exposition of the American Chemical Society (ACS), being held this week.

In a Kavli Foundation Innovations in Chemistry Lecture, Susan Solomon, Ph.D., of the University of Colorado, Boulder, said that the combined efforts of scientists, the public, industry and policy makers to stop ozone depletion is one of science’s greatest success stories, but unanswered questions remain. And ozone is still disappearing.

“We’re no longer producing the primary chemicals — chlorofluorocarbons (CFCs) — that caused the problem, but CFCs have very long lifetimes in our atmosphere, and so we’ll have ozone depletion for several more decades,” said Solomon. “There are still some remarkable mysteries regarding exactly how these chlorine compounds behave in Antarctica — and it’s amazing that we still have much to learn, even after studying ozone for so long.”

The ozone layer is crucial to life on Earth, forming a protective shield high in the atmosphere that blocks potentially harmful ultraviolet rays in sunlight. Scientists have known since 1930 that ozone forms and decomposes through chemical processes. The first hints that human activity threatened the ozone layer emerged in the 1970s, and included one warning from Paul Crutzen, Ph.D., that agricultural fertilizers might reduce ozone levels. Another hint was from F. Sherwood Rowland, Ph.D., and Mario Molina, Ph.D., who described how CFCs in aerosol spray cans and other products could destroy the ozone layer. The three shared a 1995 Nobel Prize in Chemistry for that research. In 1985, British scientists discovered a “hole,” a completely unexpected area of intense ozone depletion over Antarctica. Solomon’s 1986 expedition to Antarctica provided some of the clinching evidence that underpinned a global ban on CFCs and certain other ozone-depleting gases.

Evidence suggests that the ozone depletion has stopped getting worse. “Ozone can be thought of as a patient in remission, but it’s too early to declare recovery,” said Solomon. And surprises, such as last winter’s loss of 40% of the ozone over the Arctic still occur due to the extremely long lifetimes of ozone-destroying substances released years ago before the ban.

Solomon also took listeners on a tour of gases and aerosols that affect climate change and described how these substances can contribute to global warming.

“On the thousand-year timescale, carbon dioxide is by far the most important greenhouse gas produced by humans, but there are some other interesting — though much less abundant — gases such as perfluorinated compounds that also last thousands of years and similarly affect our climate for millennia,” said Solomon.

Increases in atmospheric “greenhouse gases” such as carbon dioxide trap heat in the atmosphere, causing Earth’s temperature to creep upward. Global warming is causing ocean levels to rise and could lead some regions to become dry “dust bowls.”

Dealing with global warming has prompted a lot of interesting research on how to reduce greenhouse gas emissions, how to adapt to a changing climate and on the possibility of ‘geoengineering’ to cool the climate.

“Recent studies on ‘geoengineering’ the Earth’s climate involve stratospheric particles of different sorts,” she said. “Most of these schemes involve sulfate particles, but other types have been proposed.”

The talk took place on Monday, August 29 in the Wells Fargo Theater at the Colorado Convention Center.

Sponsored by The Kavli Foundation, a philanthropic organization that supports basic scientific research, the lectures are designed to address the urgent need for vigorous, “outside the box” thinking by scientists as they tackle the world’s mounting challenges, including climate change, emerging diseases, and water and energy shortages.

“We are dedicated to advancing science for the benefit of humanity, promoting public understanding of scientific research, and supporting scientists and their work,” said Kavli Foundation President Robert W. Conn in a statement. “The Kavli Foundation Innovations in Chemistry Lecture program at the ACS national meetings fits perfectly with our commitment to support groundbreaking discovery and promote public understanding.”

The Kavli lectures debuted at the Anaheim meeting in March during this International Year of Chemistry and will continue through 2013. They will address the urgent need for vigorous, new, “outside-the-box”- thinking, as scientists tackle many of the world’s mounting challenges like climate change, emerging diseases, and water and energy shortages. The Kavli Foundation, an internationally recognized philanthropic organization known for its support of basic scientific innovation, agreed to sponsor the lectures in conjunction with ACS in 2010.

Spacecraft Sees Solar Storm Engulf Earth

Spacecraft Sees Solar Storm Engulf Earth – NASA Science.

August 18, 2011: For the first time, a spacecraft far from Earth has turned and watched a solar storm engulf our planet. The movie, released today during a NASA press conference, has galvanized solar physicists, who say it could lead to important advances in space weather forecasting.

“The movie sent chills down my spine,” says Craig DeForest of the Southwest Research Institute in Boulder, Colorado.  “It shows a CME swelling into an enormous wall of plasma and then washing over the tiny blue speck of Earth where we live.  I felt very small.”

CME Engulfs Earth (splash, 558px)

A wide-angle movie recorded by NASA’s STEREO-A spacecraft shows a solar storm traveling all the way from the sun to Earth and engulfing our planet. A 17 MB Quicktime zoom adds perspective to the main 40 MB Quicktime movie.

CMEs are billion-ton clouds of solar plasma launched by the same explosions that spark solar flares.   When they sweep past our planet, they can cause auroras, radiation storms, and in extreme cases power outages.  Tracking these clouds and predicting their arrival is an important part of space weather forecasting.

“We have seen CMEs before, but never quite like this,” says  Lika Guhathakurta, program scientist for the STEREO mission at NASA headquarters.  “STEREO-A has given us a new view of solar storms.”

STEREO-A is one of two spacecraft launched in 2006 to observe solar activity from widely-spaced locations. At the time of the storm, STEREO-A was more than 65 million miles from Earth, giving it the “big picture” view other spacecraft in Earth orbit have been missing.

When CMEs first leave the sun, they are bright and easy to see. Visibility is quickly reduced, however, as the clouds expand into the void.  By the time a typical CME crosses the orbit of Venus, it is a billion times fainter than the surface of the full Moon, and more than a thousand times fainter than the Milky Way.  CMEs that reach Earth are almost as gossamer as vacuum itself and correspondingly transparent.

CME Engulfs Earth (signup)

“Pulling these faint clouds out of the confusion of starlight and interplanetary dust has been an enormous challenge,” says DeForest.

Indeed, it took almost three years for his team to learn how to do it. Footage of the storm released today was recorded back in December 2008, and they have been working on it ever since.  Now that the technique has been perfected, it can be applied on a regular basis without such a long delay.

Alysha Reinard of NOAA’s Space Weather Prediction Center explains the benefits for space weather forecasting:

“Until quite recently, spacecraft could see CMEs only when they were still quite close to the sun. By calculating a CME’s speed during this brief period, we were able to estimate when it would reach Earth. After the first few hours, however, the CME would leave this field of view and after that we were ‘in the dark’ about its progress.”

“The ability to track a cloud continuously from the Sun to Earth is a big improvement,” she continues.  “In the past, our very best predictions of CME arrival times had uncertainties of plus or minus 4 hours,” she continues.  “The kind of movies we’ve seen today could significantly reduce the error bars.”

CME Engulfs Earth (zoom, 200px)

This 17 MB Quicktime zoom adds perspective to the main 40 MB Quicktime movie of the CME engulfing Earth.

The movies pinpoint not only the arrival time of the CME, but also its mass.  From the brightness of the cloud, researchers can calculate the gas density with impressive precision.  Their results for the Dec. 2008 event agreed with actual in situ measurements at the few percent level.  When this technique is applied to future storms, forecasters will be able to estimate its impact with greater confidence.

At the press conference, DeForest pointed out some of the movie’s highlights:   When the CME first left the sun, it was cavernous, with walls of magnetism encircling a cloud of low-density gas.   As the CME crossed the Sun-Earth divide, however, its shape changed.  The CME “snow-plowed” through the solar wind, scooping up material to form a towering wall of plasma. By the time the CME reached Earth, its forward wall was sagging inward under the weight of accumulated gas.

The kind of magnetic transformations revealed by the movie deeply impressed Guhathakurta:  “I have always thought that in heliophysics understanding the magnetic field is equivalent to the ‘dark energy’ problem of astrophysics.  Often, we cannot see the magnetic field, yet it orchestrates almost everything.   These images from STEREO give us a real sense of what the underlying magnetic field is doing.”

All of the speakers at today’s press event stressed that the images go beyond the understanding of a single event.  The inner physics of CMEs have been laid bare for the first time—a development that will profoundly shape theoretical models and computer-generated forecasts of CMEs for many years to come.

“This is what the STEREO mission was launched to do,” concludes Guhathakurta, “and it is terrific to see it live up to that promise.”

Author: Dr. Tony Phillips | Credit: Science@NASA

Jose Near Bermuda; Katia Up Next?

More Tropical Woes: Jose Near Bermuda; Katia Up Next?: Scientific American.

 

While Irene is posing the greatest danger to lives this weekend, it is not the only tropical woe in the Atlantic Basin. Tropical Storm Jose is nearing Bermuda, while the formation of Katia may be on the horizon.

Tropical Storm Jose formed earlier this morning, around the time Irene’s center was bearing down on the New York City area.
Jose, however, will never become the powerful storm that Irene intensified into. Strong wind shear associated with Irene will actually cause Jose to weaken into a tropical depression by Monday morning.

Regardless, Jose will graze Bermuda with minimal tropical storm-force winds and gusty bands of rain through this evening.
The rough surf that will continue to pound Bermuda into Monday has actually been kicked up by Irene, not Jose.

More Tropical Trouble Lurking
Irene and Jose are not the only tropical features the AccuWeather.com Hurricane Center is keeping a close eye on.
A tropical wave located just off the western coast of Africa could become the next tropical storm in the Atlantic Basin, acquiring the name “Katia.”

Strong wind shear is currently disrupting the wave’s ability to develop into a more organized tropical system. However, that will change in the next couple of days as the wave enters a calmer environment.

AccuWeather.com meteorologists will pinpoint the precise track of the wave as it churns through the open waters of the Atlantic during the upcoming week, threatening only shipping interests.

Any impacts to land would not occur until at least later next weekend if the wave takes a track toward the Lesser Antilles. The wave, however, may never pose a danger to land if it curves into the open waters of the central Atlantic.

This article is reprinted with permission from AccuWeather.com. It was first published on August 29, 2011.

The Worst Solar Storms in History

The Sun’s Wrath: Worst Solar Storms in History | Sun Storms & Solar Flares | Space Weather, Carrington Event & Bastille Day Flare | Space.com.

Sunspots sketched by Richard Carrington on Sept. 1, 1859.

Credit: Royal Astronomical Society/Richard Carrington via NASA

The Carrington Event of 1859 was the first documented event of a solar flare impacting Earth. The event occurred at 11:18 a.m. EDT on Sept. 1 and is named after Richard Carrington, the solar astronomer who witnessed the event through his private observatory telescope and sketched the sun’s sunspots at the time. The flare was the largest documented solar storm in the last 500 years, NASA scientists have said.

According to NOAA, the Carrington solar storm event sparked major aurora displays that were visible as far south as the Caribbean. It also caused severe interruptions in global telegraph communications, even shocking some telegraph operators and sparking fires when discharges from the lines ignited telegraph paper, according to a NASA description.

1972: Solar Flare vs. AT&T

 

August 1972 solar flare.

Credit: NASA

The major solar flare that erupted on Aug. 4, 1972 knocked out long-distance phone communication across some states, including Illinois, according to a NASA account.

“That event, in fact, caused AT&T to redesign its power system for transatlantic cables,” NASA wrote in the account.

1989: Major Power Failures From Solar Flare

 

Damage from the March 13, 1989 geomagnetic storm caused by an intense solar flare.

Credit: NASA/PSE&G

In March 1989, a powerful solar flare set off a major March 13 power blackout in Canada that left six million people without electricity for nine hours.

According to NASA, the flare disrupted electric power transmission from the Hydro Québec generating station and even melted some power transformers in New Jersey. This solar flare was nowhere near the same scale as the Carrington event, NASA scientists said.

Sun's magnetic loops during Bastille Day storm,

Credit: NASA/TRACE

The Bastille Day event takes its name from the French national holiday since it occurred the same day on July 14, 2000. This was a major solar eruption that registered an X5 on the scale of solar flares.

The Bastille Day event caused some satellites to short-circuit and led to some radio blackouts. It remains one of the most highly observed solar storm events and was the most powerful flare since 1989.

Halloween Solar Flare of October 2003

Credit: NASA/SOHO

On Oct. 28, 2003, the sun unleashed a whopper of a solar flare. The intense sun storm was so strong it overwhelmed the spacecraft sensor measuring it. The sensor topped out at X28, already a massive flare), but later analysis found that the flare reached a peak strength of about X45, NASA has said.

The solar storm was part of a string of at least nine major flares over a two-week period.

2006: X-Ray Sun Flare for Xmas

 

Solar Flare Surprise: Pure Hydrogen Shot at Earth

Credit: NOAA’s Space Weather Prediction Center.

When a major X-class solar flare erupted on the sun on Dec. 5, 2006, it registered a powerful X9 on the space weather scale.

This storm from the sun “disrupted satellite-to-ground communications and Global Positioning System (GPS) navigation signals for about 10 minutes,” according to a NASA description.

The sun storm was so powerful it actually damaged the solar X-ray imager instrument on the GOES 13 satellite that snapped its picture, NOAA officials said.

 

 

 

 

 

 

Climate Change Endangers Cutthroat Trout

Iconic Fishes Face New Threat – ScienceNOW.

They’re not spectacular like marlins, but trout are among the most legendary—think A River Runs Through It—and lucrative fish of mountain rivers and lakes. Across the western United States alone, trout fishing generates hundreds of millions of dollars annually. But trout habitat will likely be cut in half by 2080 due to warming rivers and altered patterns of flooding, according to a large study published today. “It’s fairly shocking to us, as biologists,” says co-author Kurt Fausch of Colorado State University, Fort Collins.

The study, published online today in the Proceedings of the National Academy of Sciences, is the first to tease apart the probable impacts of climate change on common trout species. This is not a case of winners and losers; the four species examined by the team are all likely to decline to varying degrees. The good news for fans of fly-fishing is that the rainbow trout, beloved for its large size, will suffer the smallest impact. On the other hand, the results will further alarm conservationists concerned about the plight of native cutthroat trout.

By running several climate models and plugging in data on habitat characteristics and fish present at 9890 locations in the Rocky Mountains and Great Basin, the team of scientists created predictions for trout habitat across more than 1 million square kilometers of the western United States. They factored physical aspects of habitat—water temperature, patterns of flooding—as well as competition among species. Here’s what the study concludes about the future of trout:

Rainbow trout (Oncorhynchus mykiss): Introduced beginning in the 1800s for fishing, these trout live in larger rivers than do the other species. They typically grow up to 110 centimeters long and are relatively easy to catch.Increases in water temperature will restrict their range, but rainbow trout dodge a bullet. Climate change will mean more frequent and intense winter floods, which can scour away eggs laid in the fall, but rainbow trout spawn in the spring. The size of their habitat is predicted to decline by 35%.

Brown trout (Salmo trutta): Smaller than rainbow trout, they are the most temperature tolerant among the four species and like warmer temperatures. They have the ill fortune to spawn in the fall, so the increased flooding will make many streams inhospitable. Their habitat is predicted to decline by 48%.

Cutthroat trout (Oncorhynchus clarkii): The range of these native fish has already shrunk by more than 85% due to competition from introduced species. Two subspecies have already gone extinct. Warming temperatures and continued competition primarily from rainbow trout are predicted to reduce suitable habitat by a further 58%.

Brook trout (Salvelinus fontinalis): Runts compared with the other species, brook trout are the biggest losers in 2080. Because they spawn in the fall, the increase in winter flooding is expected to reduce their suitable habitat by 77%—a surprising amount given their success at invading new habitat. “I did not expect brown trout to decline so much,” says co-author Seth Wenger, a biologist with Trout Unlimited, a conservation organization in Boise.

Frank Rahel, a fish ecologist at the University of Wyoming in Laramie, who was not involved with the study, says the findings help paint the big picture for trout this century. “They’re very sobering results that will catch people’s attention,” he says. Not much can be done to reduce the impact of winter floods, but managers already try to keep streams cooler by planting trees and shrubs.