Sunday, January 27, 2013
F.D.A. Panel Recommends Restrictions on Hydrocodone Products Like Vicodin
[unable to retrieve full-text content]An advisory panel to the Food and Drug Administration voted 19 to 10 to recommend increased restrictions on hydrocodone products, the country?s most widely used narcotic painkillers.
Crystal Cruises entices bookings through brand ... - Luxury Daily
Crystal Symphony
Crystal Cruises is eyeing affluent travelers by offering exclusive Mediterranean excursions on its spring itineraries that cannot be accessed through other travel brands.
The cruise line?s new collection of experiences called ?Boutique Adventures? will be available this spring for groups ranging from one to 15 travelers on Crystal Symphony and Crystal Serenity ships sailing to the Mediterranean. Guests will have exclusive access to estates, art studios, museums, castles and businesses.
?Our guests are looking for different ways to experience destinations and they relish insider access,? said Mimi Weisband, vice president of public relations at?Crystal Cruises, Los Angeles. ?We are continually challenging our tour operators to seek out the unusual, experiential, intimate, cultural adventures.
?Our guests do not want a mass-market excursion ? they will pay more for something if it is unique and authentic,? she said.
Cruising the Mediterranean
There are seven Boutique Adventures that guests can choose. The cost ranges from $223 to more than $1,000 per guest.
Travelers can book the excursions online up to six months before their cruise.
The Florence excursion comprises a viewing of the Uffizi Gallery?s private Contini Bonacossi Collection, which is not accessible to the public.
In Funchal, Portugal, guests will have lunch with a local celebrity at Reid?s Palace or visit a family-run Madeiran winery where they will dine with the owners.
During the Rome experience, guests will make their own jewelry with instruction from a former Valentino model who now designs jewelry.
The Corfu, Greece, excursion consists of a painting lesson from the president of the Corfu Painters Society.
In Italy?s Vetriano, guests will attend the opera at Teatro Concordia, the?smallest public theater in the world.
Teatro Concordia
Excursions in Sorrento and Taormina, Italy, comprise?cooking lessons and meals with local, Michelin-star chefs.
In Taormina in Italy?s Sicily region, travelers will be served a meal while watching a classical concert at a Sicilian castle.
Crystal Cruises will promote the Boutique Adventures via its Web site, quarterly magazine and the on-board Shore Excursion team, per Ms. Weisband.
In addition, travel agents will also inform their clients about the experiences.
?The cruise industry has been becoming more aware of the large portion of the affluent travelers who shy away from cruises due to many misconceptions and overall lack of desire to be on-board the mega-ships,? said D.M. Banks, director at?DMB Public Relations, New York.
?Crystal Cruises is always looking at ways to provide the luxuries of cruises, while providing a boutique experience for their guests,? he said. ?This is another example of them thinking outside of the box to truly connect with their guests.
?Affluent travelers are more than happy to pay a premium for superior services and, more importantly, unique and personalized experiences. These intimate and semi-private excursions are great ways for guest to feel more immersed into the culture and destinations while at port.?
Story time
The new Boutique Adventures are meant to align with Crystal Cruises? ?Begin a New Story? ad campaign that launched last year, per Ms. Weisband.
The cruise line rebranded itself during the second quarter of 2012 through an all-encompassing campaign that centers on the notion of the travel journal and encourages consumers to share memories from past cruises.
The marketing efforts focus on cruise destinations and once-in-a-lifetime experiences, rather than the amenities of the ship.
Begin a New Story uses multiple channels including print ads with digital watermark technology, brochures, online banner ads, email, video and a smartphone app.
For instance, print ads appear in Cond? Nast Traveler, National Geographic Traveler, Town & Country, Travel & Leisure, Coastal Living, Elle D?cor, Food & Wine and Forbes Life.
Consumers can scan the ads with their smartphones to reveal a 60-second video that shows three travelers? experiences in select Crystal Cruises? destinations through watercolor animation.
The brand asked eight watercolor artists to create images that are used in all aspects of the campaign (see story).
?The trend for affluent consumers is more intimate and incredibly special ? both of which are key to these excursions,? Ms. Weisband said.
?Entering someone?s home, sharing a meal with them and just a few other guests, and being able to hear in-depth stories of living and working in that area from your host ? these are experiences that can be deeply personal, bonding and memorable, really expanding one?s understanding of a culture far beyond any info gleaned from merely sight-seeing,? she said.
?Affluent consumers crave such experiences that go beyond the norm, as so many of them travel at a level well above the basics.?
Final Take
Tricia Carr, editorial assistant on Luxury Daily, New York
Tricia Carr is an editorial assistant on Luxury Daily. Her beats are apparel and accessories, arts and entertainment, education, food and beverage, fragrance and personal care, government, healthcare, home furnishings, jewelry, legal/privacy and nonprofits. Reach her at tricia@napean.com.
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Tags: Begin a New Story, Boutique Adventures, Crystal Cruises, Crystal Serenity, Crystal Symphony, In-store, luxury, luxury marketing, luxury travel, Mediterranean travel, Mimi Weisband, travel and hospitality, travel marketing
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Saturday, January 26, 2013
Jindal: 'Stop Being The Stupid Party'
By MICHAEL FALCONE ( @michaelpfalcone )
NOTABLES:
BREAKING - OBAMA TO ANNOUNCE CHIEF OF STAFF: From the White House: "This afternoon, the President will introduce Denis McDonough as the new White House Chief of Staff. The President will make this personnel announcement at the White House at 12:10 PM in the East Room. Denis has been one of the President's closest and most trusted advisors for nearly a decade, dating back to when he helped set up then Senator's Barack Obama's Senate office. He has relied on his intellect and good judgment ever since- most recently as a member of the President's national security team. In that capacity, Denis has played a key role in all of the major national security decisions - from ending the war in Iraq to winding down the war in Afghanistan; from our response to natural disasters in Haiti and Japan; to the repeal of 'Don't Ask, Don't Tell.'"
FORMER DEFENSE SECRETARY, NATIONAL SECURITY OFFICIALS ENDORSE HAGEL. Chuck Hagel, President Obama's controversial secretary of Defense nominee, received a boost on Thursday, ABC's Jonathan Karl reports: Former Secretary of Defense Robert Gates - who served under both George W. Bush and Barack Obama - has signed on to a letter with a bi-partisan group of 12 other former top national security officials expressing his "strong endorsement" of Chuck Hagel for Secretary of Defense. The list also includes several top national security officials for Republican presidents: Brent Scrowcroft (Bush 41), Mel Laird (Nixon), George Schultz (Reagan), Colin Powell (Reagan, Bush 41 and Bush 43), Robert McFarlane (Reagan). It's a pretty formidable list. http://abcn.ws/WS4iWP
HAPPENING TODAY: Vice President Joe Biden, Secretary of Homeland Security Janet Napolitano, Secretary of Health and Human Services Kathleen Sebelius, Deputy U.S. Attorney General Jim Cole, and other Obama administration officials will hold a roundtable discussion on reducing gun violence at Virginia Commonwealth University in Richmond, Va. Sen. Tim Kaine, D-Va., and Rep. Bobby Scott, D-Va., will also attend. According to the White House, the session will include experts who have worked on gun safety issues in the wake of the Virginia Tech shooting.
THIS WEEK ON 'THIS WEEK': After Hillary Clinton faced off with Congress on Benghazi, Sen. John McCain, R-Ariz., and Sen. Robert Menendez, D-N.J., of the Foreign Relations Committee speak to ABC News Chief Global Affairs correspondent Martha Raddatz, Sunday on "This Week." And the powerhouse roundtable debates all the week's politics, with ABC News' George Will; Rep. David Schweikert, R-Ariz.; Democratic strategist and ABC News contributor Donna Brazile; NPR "Morning Edition" host Steve Inskeep; and New Republic owner and publisher Chris Hughes, who interviewed President Obama for an Oval Office exclusive on newsstands next week. Plus, "Zero Dark Thirty" screenwriter Mark Boal and "Blackhawk Down" author Mark Bowden discuss the controversy over the Oscar-nominated film. Tune in Sunday: http://abcnews.go.com/thisweek
THE ROUNDTABLE:
ABC's MICHAEL FALCONE: Although Louisiana Gov. Bobby Jindal is already the subject of speculation as a potential GOP presidential contender four years from now, if you ask him, it's way too soon for speculating. "Any Republican that's thinking about running for president in 2016 needs to get his head examined," Jindal told reporters after delivering a dinner speech at the Republican National Committee winter meeting last night. He added, "We've got a lot of work between now and the next midterm elections. ? We've got to get the Republican Party back on track." In his remarks to the gathering, he also offered some tough medicine for the GOP, including this piece of advice: "We must stop being the stupid party. It's time for a new Republican party that talks like adults. It's time for us to articulate our plans and visions for America in real terms. We had a number of Republicans damage the brand this year with offensive and bizarre comments. We've had enough of that." Whether or not Jindal ultimately emerges as a top presidential contender, look for him to be a major presence, not just in Louisiana, but around the country as well as a key figure in helping the party chart its course forward.
ABC's Z. BYRON WOLF: There's a bit of irony - if that's the right word - in the fact that it took fewer than 12 hours for senators to hatch, agree, and vote on a deal to tweak filibuster rules. The filibuster technically allows the minority to engage in unlimited debate. But changing the filibuster got barely any debate at all. Then again, the filibuster didn't really change. The deal passed overwhelmingly last night creates new rules to grease the arcane and usually slow-moving cogs of the "World's Greatest Deliberative Body." But 40 votes can still block anything. Would-be reformers say these rule changes are weak sauce. But it may represent a recognition in the Senate that things aren't really working the way they're supposed to.
ABC's RICK KLEIN: Can we get a round of applause for being quiet? Mitt Romney is in Washington today, of course a few days later than he wanted to have been in town, and on a far more temporary basis. What's remarkable, though, is how silent he's been in the 10-plus weeks since he didn't win the presidency. Save for a phone call with supporters that he didn't expect to come out - the one about the "gifts" that supposedly helped President Obama win a second term - we haven't heard Romney's voice at all since the election. He was not invited to the inauguration, and without a federal office he's holding, there would have been no reason for him to attend. There will be a time when Romney has something meaningful to contribute to the public dialog on, or something to reflect on or unburden himself with. In the meantime, until he feels like he has something to add, silence is worth savoring.
BUZZ
with ABC's Chris Good ( @c_good)
JOE BIDEN'S 'FIRESIDE HANGOUT': GUNS, EARTHQUAKES. ABC's Arlette Saenz reports: Sitting in front of a fireplace, Vice President Joe Biden participated in his first ever Google+ "Fireside Hangout" Thursday in his most recent attempt to push the administration's gun policy agenda, one that he said is focused on "gun safety" not "gun control." "I don't view it as gun control. I view it as gun safety," Biden said in a Google+ "Fireside Hangout" on gun violence. ? "My view is that it is totally a guarantee, not negotiable, that I'm able to own a weapon for sporting purposes as well as for my own protection, but there should be rational limits on the type of weapon" needed for protection or sports, he said. ? the vice president doled out a bit of advice for how to protect oneself after a deadly earthquake, telling one questioner a shotgun is more effective than an assault weapon. "If you want to keep people away during an earthquake, buy some shotgun shells," Biden said. http://abcn.ws/WpFAfn
PANETTA MAKES IT OFFICIAL: WOMEN WILL BE ABLE TO SERVE IN COMBAT. From ABC's Chris Good, Luis Martinez, and Mary Bruce: Women will soon be able to serve in combat, as things officially changed with the stroke of a pen today at the Pentagon. At a joint news conference, Secretary of Defense Leon Panetta and Joint Chiefs of Staff Charman Gen. Martin Dempsey signed a memorandum rolling back a 1994 directive prohibiting women from doing so. "They serve, they're wounded, and they die right next to each other," Panetta said of women and men in the military. "The time has come to recognize that reality. "If they're willing to put their lives on the line, then we need to recognize that they deserve a chance," Panetta said ? The change won't be immediate, however. While Panetta announced that thousands of new positions will now be open to women, he has asked the military branches to submit plans by May on how to integrate women into combat operations. He set a January 2016 deadline for branches to implement the changes, giving military services time to seek waivers for certain jobs. http://abcn.ws/WRuVuZ
OBAMA APPLAUDS THE MOVE. Obama hailed the move in a written statement. "Today, by moving to open more military positions - including ground combat units - to women, our armed forces have taken another historic step toward harnessing the talents and skills of all our citizens," he said. "This milestone reflects the courageous and patriotic service of women through more than two centuries of American history and the indispensable role of women in today's military," Obama said. "As commander in chief, I am absolutely confident that-as with the repeal of 'Don't Ask, Don't Tell'-the professionalism of our armed forces will ensure a smooth transition and keep our military the very best in the world," the president said. "Today, every American can be proud that our military will grow even stronger with our mothers, wives, sisters and daughters playing a greater role in protecting this country we love." http://abcn.ws/WRuVuZ (h/t ABC's Mary Bruce)
REPUBLICAN PARTY SET TO RE-ELECT CHAIR: Members of the Republican National Committee who have gathered for their winter meeting in Charlotte, N.C. today are poised to re-elect current Chairman Reince Priebus for another two-year term this afternoon. Priebus, the 40-year-old Wisconsin native who was elected to head the party in 2011, did not preside over a period that saw a winning Republican presidential candidate, but he did lead his party out of a deep hole of debt - more than $20 million left by former RNC Chairman Michael Steele. Chairman Priebus plans to deliver a speech to the meeting today and one of his big themes will be about how Republicans need to stay on a campaign footing at all times."Simple outreach' a few months before an election will not suffice," Priebus plans to tell the gathering, according to excerpts of his remarks. "In fact, let's stop talking about 'reaching out' - and start working on welcoming in. Political support is cultivated over time - not collected on Election Day." Chairman Priebus will also issue this call: "To those who have left the party, we want to earn your trust again. To those who have yet to join us, we welcome you-with open doors and open arms."
POST-ELECTION DATA WAR: TECHIES VS. POLS. The Verge's Ben Popper reported this week that Democratic operatives and Obama's tech team are fighting over what to do with the code that helped elect Obama: "[I]n the aftermath of the election, a stark divide has emerged between political operatives and the techies who worked side-by-side. At issue is the code created during the Obama for America (OFA) 2012 campaign: the digital architecture behind the campaign's website, its system for collecting donations, its email operation, and its mobile app. When the campaign ended, these programmers wanted to put their work back into the coding community for other developers to study and improve upon. Politicians in the Democratic party felt otherwise, arguing that sharing the tech would give away a key advantage to the Republicans. Three months after the election, the data and software is still tightly controlled by the president and his campaign staff, with the fate of the code still largely undecided. It's a choice the OFA developers warn could not only squander the digital advantage the Democrats now hold, but also severely impact their ability to recruit top tech talent in the future." http://bit.ly/UPNLDg
WHITE HOUSE, CONGRESSIONAL HISPANIC CAUCUS TO MEET ON IMMIGRATION. The Huffington Post's Elise Foley reports: "The White House will meet on Friday with members of the Congressional Hispanic Caucus to discuss immigration reform. The meeting, one of many between President Barack Obama's administration and Hispanic members of Congress, adds steam to Obama's inaugural pledge to push for immigration reform. Members of the Congressional Hispanic Caucus have provided guidance for the president in the past. The president's schedule for Friday says he will be at the White House in meetings, but does not specify whether he will speak with Hispanic Caucus members. The meeting was confirmed to The Huffington Post by Democratic sources not authorized to speak on the record about the meeting." http://huff.to/10W3mHx
WHY IS HILLARY CLINTON WEARING GLASSES? If you noticed the glasses Hillary Clinton wore during her appearances on the Hill to talk about Benghazi, ABC's Dana Hughes reports: "She'll be wearing these glasses instead of her contacts for a period of time because of lingering issues stemming from her concussion. With them on she sees just fine. In fact, she got a kick out of the above when she saw them crystal clear," Clinton spokesman Philippe Reines has confirmed.
PHOTOS: JOHN KERRY TESTIFYING, 1971 AND TODAY. Thanks, BuzzFeed's Andrew Kaczynski: http://bit.ly/14dQx9B
TOM TANCREDO SAYS HE'LL SMOKE POT. Former congressman Tom Tancredo says he'll honor a bet to smoke marijuana. In a video to promote Colorado's Amendment 64, which legalized the personal use of marijuana in the state, Tancredo reportedly pledged to smoke pot if the measure passed. Tancredo, a self-professed non-marijuana-smoker, supported the measure. "Look, I made a bet with the producer of the film that if Amendment 64 passed (I did not think it would) that I would smoke pot," Fox News quotes Tancredo as saying. "I will therefore smoke pot under circumstances we both agree are legal under Colorado law. Hey, it's better than having to do a stupid dance as [Denver] Mayor [Michael] Hancock must perform as a result of losing a bet on the Broncos beating the Ravens." http://abcn.ws/14aH2su
MEMO TO FLIES: DON'T BUG OBAMA! Something was bugging President Obama yesterday as he nominated Mary Jo White to head the Securities and Exchange Commission and re-nominated Richard Cordray to lead the Consumer Financial Protection Bureau, ABC's Mary Bruce notes. "This guy is bothering me here," the president said, as he repeatedly swatted at a large black fly buzzing near his face. Given Obama's reputation, it was a bold move for the insect to spar with the "swatter in chief."During a June 2009 CNBC interview, Obama famously killed a fly with a single smack. "Get out of here," the president ordered of the fly before the interview began. When the directive was ignored, Obama waited for the fly to land on his hand and then, "slap," swiftly ended its life with a single blow. "That was pretty impressive, wasn't it?" Obama proudly declared. "I got the sucker." (PETA later condemned the move). The fly in the State Dining Room today was lucky enough to avoid a similar fate. http://abcn.ws/11UGiYQ
WHO'S TWEETING?
@mckaycoppins: ICYMI: Marco Rubio Backs Women In Combat http://bit.ly/VmV0Gw via @dcbigjohn
@Goldfarb: EXCLUSIVE: Geithner's private farewell to Obama, Treasury http://www.washingtonpost.com/blogs/wonkblog/wp/2013/01/25/exclusive-geithners-private-farewell-to-obama-and-treasury-staff/ ?
@jonward11: Energy Drinks Hire Lobbyists To Fend Off Regulation by @christinawilkie http://www.huffingtonpost.com/mobileweb/2013/01/24/energy-drinks-lobbyists-regulation_n_2546622.html?1359082273 ?
@ByronYork: In '08, NC gov candidate Pat McCrory was swamped in Obama wave. Went back to basics, figured out how to win in '12? http://ow.ly/h7IZv
@jmartpolitico: . @RahmEmanuel is putting pressure on banks that do biz w gun makers to nudge their clients to support gun control http://politi.co/WUe9v3
Also ReadThin is in with the Flatlight flashlight
Bucking traditions in the flashlight form factor, Flatlight, a Kickstarter project by Tater Tot Designs,?brings in the thin. The Flatlight is 3.57″ X 1.99″ X 0.11″, giving it a credit card-like profile. An array of LED transmits light to a fiber optic backlight that evenly distributes the light through the lens. Although I don’t think [...]
Source: http://the-gadgeteer.com/2013/01/25/thin-is-in-with-the-flatlight-flashlight/
Seizure of counterfeit sports apparel part of Super Bowl buzz - News ...
Posted: Jan. 25, 2013 | 8:51 a.m.
During the days leading up to this year's Super Bowl on Feb. 3, you can count on three things - a litany of stories on the teams' two coaches who just happen to be brothers, buzz about TV commercials that will cost $4 million and the feds cracking down on street vendors hawking phony, unlicensed NFL jerseys, shirts and hats.
Such was the case Friday when federal agents and Las Vegas police displayed counterfeit sports gear ranging from Chicago Bears and New York Jets jerseys to bags bearing the logos of the Pittsburgh Steelers, Denver Broncos and Green Bay Packers.
In all, about 600 fake items with a retail value of $15,000 were confiscated three days earlier by U.S. Immigration and Customs Enforcement, Homeland Security Investigations and Las Vegas police officials. Agents said Mustafa Ahmadi, 31, and Sonia Qudrat, 29, used a screen press at a Fremont Street Experience kiosk in downtown Las Vegas to apply professional sports teams logos downloaded off the Internet to shirts, jerseys, hats and scarves.
The two were arrested on charges of selling counterfeit goods and face a Class D felony, punishable by up to one to four years in prison and a $5,000 fine.
Sports retailers who sell legitimate licensed NFL and other sports gear celebrated.
"I was jumping for joy. This is awesome," said Bruce Mianecki, owner of Uniform Sports, a retail store in the Las Vegas Premium Outlets South.
Mianecki said he reported the kiosk vendors to his Nike representatives in hopes authorities would be alerted. Nike is the NFL supplier of licensed jerseys. Mianecki said he also has contacted Craigslist about people selling phony, unlicensed NFL gear on that website.
"I have to compete with these guys. They undercut me. They sell a jersey for $40 or $60, and my top jersey goes for $250. And they're not putting any money into the tax base," Mianecki said.
Federal authorities are cracking down on phony sports logo gear in 30 other cities as part of its national Operation Red Zone program.
The NFL, which hires local companies to identify vendors pitching unlicensed merchandise in dozens of markets nationwide, lauded Friday's news.
"We appreciate the effort from federal and local authorities in taking these counterfeit items off the streets," NFL spokesman Brian McCarthy said. "These counterfeiters aren't graphic artists - they're con artists. Our fans deserve the best from the NFL, and these counterfeiters dupe them into buying inferior merchandise and also harm local retailers."
Vendors selling phony gear hurts the city's tourism economy because unsuspecting tourists buy inferior, unlicensed merchandise and don't return because of the negative experience, said Las Vegas police Detective Robert Sigal, who worked on the case.
"They won't come back to the city," Sigal said. "We want them to leave with good memories."
Authorities said the arrested vendors made thousands of dollars from the sports knockoffs for the past few months. A month ago, federal agents also seized phony NFL jerseys that were sent from China and bound for a Henderson man.
Michael Harris, assistant special agent in charge, said the counterfeit sports gear is just a slice of a bigger illegal movement of phony merchandise that ranges from fake car parts and contact lenses to medicine.
U.S. retailers lose $200 billion to $250 billion annually in sales because of phony merchandise, Harris said.
Steven Sampilo, a Homeland Security special agent involved in the sports gear crackdown, said there is another dubious element: "A lot of counterfeiting supports terrorism."
Contact reporter Alan Snel at asnel@reviewjournal.com or 702-387-5273.
Source: http://www.lvrj.com/news/authorities-seize-counterfeit-sports-apparel-188366291.html
New tool for mining bacterial genome for novel drugs
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Public release date: 25-Jan-2013[ | E-mail |
Share ] Contact: David Salisbury
david.salisbury@vanderbilt.edu
615-343-6803
Vanderbilt University
Vanderbilt biochemists have discovered that the process bacteria undergo when they become drug resistant can act as a powerful tool for drug discovery.
Their findings reported this week in the Online Early Edition of the Proceedings of the National Academy of Sciences should give a major boost to natural products drug discovery the process of finding new drugs from compounds isolated from living organisms by substantially increasing the number of novel compounds that scientists can extract from individual microorganisms.
Bacteria have traditionally been the source of important drugs such as antibiotics and anticancer agents. Researchers looking for new bacterially synthesized drugs have long known that bacterial genomes contain a large number of "silent genes" that contain the instructions for making drug-like compounds. But, until now, scientists have found it is very difficult to find ways to turn on the production of these compounds, known as secondary metabolites.
While investigating how bacteria develop drug resistance, Vanderbilt biochemists Brian Bachmann and John McLean discovered that strains of antibiotic-resistant bacteria express hundreds of compounds not produced by their progenitors, many of which are potential secondary metabolites.
"It's as if the bacteria respond to the assault by the antibiotic with a 'save-all-ships' strategy of turning on hundreds of silent genes," said Bachmann, associate professor chemistry at Vanderbilt.
"This technique is something like fracking in the natural gas industry. We've known for a long time that there were large amounts of underground natural gas that we couldn't extract using conventional methods but now we can, using hydraulic fracturing technology. In a similar fashion we think we can use bacteria's antibiotic resistance to intensively mine the bacterial genome for new drug leads," he said.
The original purpose of the study was to take the most detailed look yet at what happens when microbes develop drug resistance. Bachmann is an expert in natural products drug discovery and McLean, an assistant professor of chemistry, is a pioneer in the development of analytical instrumentation and chemical techniques that can identify thousands of different biological compounds simultaneously, such as ion mobility-mass spectrometry.
"One of the daunting challenges is to rapidly inventory the tens to hundreds of thousands of molecules the bacteria construct to live, and then to read this inventory to understand how the bacteria compensate for their changing circumstances. To complicate matters further, we are looking for new drug-like molecules, so by definition we are looking for something that has not been seen before," said McLean.
Working with Research Assistant Dagmara Derewacz and graduate students Cody Goodwin and Ruth McNees, Bachmann and McLean started with the well-characterized soil bacterium Nocardiopsis. They exposed the bacterium to two different antibiotics streptomycin and rifampicin and observed the results.
"The first thing that happens is almost all of the bacteria die. Less than one cell in a million survives," said Bachmann.
The chemists then cultured the survivors (six streptomycin-resistant strains and five rifampicin-resistant strains) without the antibiotic and used McLean's instrumental methods to profile the drug-like compounds that they produced.
They discovered that the differences were much greater than they expected. The survivors had undergone extensive mutations, not only in the genes that produce secondary metabolites but also in the housekeeping genes that alter the way they make RNA and proteins. As a result, they determined that the resistant strains produced more than 300 compounds that were not expressed by the original organism.
"The cells appear to be 'de-repressing' as many of their silent genes as possible. This seems like a very drastic way to become drug resistant," Bachmann said.
McLean's team has developed strategies that allow them to automatically identify and compare the relative uniqueness and the relative abundance of tens of thousands of molecules from which the hundreds of novel compounds were found.
"What we are looking for are new species of molecules in the mutants that are the most unique and the most abundant," said Bachmann.
In the antibiotic-resistant Nocardiopsis strains the researchers found a total of five compounds that were both unique enough and abundant enough to isolate, determine their molecular structures and test for biological activity. "Normally, we only find one compound per organism, so this is a significant improvement in yield, allowing us to get many new compounds from previously mined microorganisms," Bachmann said.
###
The research was supported by National Institutes of Health grants 1R01GM09221B and RC2DA028981 and theDefense Threat Reduction Agency grant HDTRA-09-1-0013.
Visit Research News @ Vanderbilt for more research news from Vanderbilt. [Media Note: Vanderbilt has a 24/7 TV and radio studio with a dedicated fiber optic line and ISDN line. Use of the TV studio with Vanderbilt experts is free, except for reserving fiber time.]
[ | E-mail | Share ] ?
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
Public release date: 25-Jan-2013[ | E-mail |
Share ] Contact: David Salisbury
david.salisbury@vanderbilt.edu
615-343-6803
Vanderbilt University
Vanderbilt biochemists have discovered that the process bacteria undergo when they become drug resistant can act as a powerful tool for drug discovery.
Their findings reported this week in the Online Early Edition of the Proceedings of the National Academy of Sciences should give a major boost to natural products drug discovery the process of finding new drugs from compounds isolated from living organisms by substantially increasing the number of novel compounds that scientists can extract from individual microorganisms.
Bacteria have traditionally been the source of important drugs such as antibiotics and anticancer agents. Researchers looking for new bacterially synthesized drugs have long known that bacterial genomes contain a large number of "silent genes" that contain the instructions for making drug-like compounds. But, until now, scientists have found it is very difficult to find ways to turn on the production of these compounds, known as secondary metabolites.
While investigating how bacteria develop drug resistance, Vanderbilt biochemists Brian Bachmann and John McLean discovered that strains of antibiotic-resistant bacteria express hundreds of compounds not produced by their progenitors, many of which are potential secondary metabolites.
"It's as if the bacteria respond to the assault by the antibiotic with a 'save-all-ships' strategy of turning on hundreds of silent genes," said Bachmann, associate professor chemistry at Vanderbilt.
"This technique is something like fracking in the natural gas industry. We've known for a long time that there were large amounts of underground natural gas that we couldn't extract using conventional methods but now we can, using hydraulic fracturing technology. In a similar fashion we think we can use bacteria's antibiotic resistance to intensively mine the bacterial genome for new drug leads," he said.
The original purpose of the study was to take the most detailed look yet at what happens when microbes develop drug resistance. Bachmann is an expert in natural products drug discovery and McLean, an assistant professor of chemistry, is a pioneer in the development of analytical instrumentation and chemical techniques that can identify thousands of different biological compounds simultaneously, such as ion mobility-mass spectrometry.
"One of the daunting challenges is to rapidly inventory the tens to hundreds of thousands of molecules the bacteria construct to live, and then to read this inventory to understand how the bacteria compensate for their changing circumstances. To complicate matters further, we are looking for new drug-like molecules, so by definition we are looking for something that has not been seen before," said McLean.
Working with Research Assistant Dagmara Derewacz and graduate students Cody Goodwin and Ruth McNees, Bachmann and McLean started with the well-characterized soil bacterium Nocardiopsis. They exposed the bacterium to two different antibiotics streptomycin and rifampicin and observed the results.
"The first thing that happens is almost all of the bacteria die. Less than one cell in a million survives," said Bachmann.
The chemists then cultured the survivors (six streptomycin-resistant strains and five rifampicin-resistant strains) without the antibiotic and used McLean's instrumental methods to profile the drug-like compounds that they produced.
They discovered that the differences were much greater than they expected. The survivors had undergone extensive mutations, not only in the genes that produce secondary metabolites but also in the housekeeping genes that alter the way they make RNA and proteins. As a result, they determined that the resistant strains produced more than 300 compounds that were not expressed by the original organism.
"The cells appear to be 'de-repressing' as many of their silent genes as possible. This seems like a very drastic way to become drug resistant," Bachmann said.
McLean's team has developed strategies that allow them to automatically identify and compare the relative uniqueness and the relative abundance of tens of thousands of molecules from which the hundreds of novel compounds were found.
"What we are looking for are new species of molecules in the mutants that are the most unique and the most abundant," said Bachmann.
In the antibiotic-resistant Nocardiopsis strains the researchers found a total of five compounds that were both unique enough and abundant enough to isolate, determine their molecular structures and test for biological activity. "Normally, we only find one compound per organism, so this is a significant improvement in yield, allowing us to get many new compounds from previously mined microorganisms," Bachmann said.
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The research was supported by National Institutes of Health grants 1R01GM09221B and RC2DA028981 and theDefense Threat Reduction Agency grant HDTRA-09-1-0013.
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Source: http://www.eurekalert.org/pub_releases/2013-01/vu-ntf012513.php
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