Study of staph shows how bacteria evolve resistance

Jun 04, 2007

Antibacterial resistance doesn’t happen overnight. But until recently nobody knew exactly how long it took — or how it happened at all. Now, by studying blood taken from a single patient over a period of months, Rockefeller University researchers have been able to trace how a common strain of bacteria adapted its genes to counteract the antibiotics used to try to kill it, until it finally emerged into the kind of fully resistant microbe that is wreaking havoc in hospitals worldwide. Total elapsed time: 90 days.

This is the first time that such a process has been observed “within” a patient, and the results, published in the May 21 issue of the Proceedings of the National Academy of Sciences sheds light on how such resistance occurs through selective pressure, says the study’s lead investigator, Alexander Tomasz, head of the Laboratory of Microbiology at Rockefeller University.

“What is thrilling is that we got as close as one can to the birthplace of antibiotic resistance in a patient, and now we can study which of the genetic mutations we found are really essential for resistance,” Tomasz says. If the genetic alterations they discovered are common to all known mutated strains of the bacteria — which Tomasz suspects is true — then knowing these genes may help clinicians design ways to block multidrug resistance, he says.

The microbe they isolated is Staphylococcus aureus, which is one of the most frequent causes of a wide range of hospital- and community-acquired infections, and is best known as the cause of toxic shock syndrome. The pathogen has acquired resistance to the majority of available antibiotics, including, recently, vancomycin, which was believed to be the only major agent that could treat it. “It has fantastic adaptive capabilities which have led to the worldwide spread of resistant lineages that are posing serious limits to clinical treatment,” Tomasz says.

But no one has known how such resistance occurs — whether it happens within individual patients, or whether patients with wounds pick up resistant microbes that have somehow infiltrated hospitals.

In this study, Tomasz, along with first author Michael Mwangi, a postdoc in the Tomasz lab, Eric Siggia, head of the Laboratory of Theoretical Condensed Matter Physics, and collaborators from Rockefeller, the Howard Hughes Medical Institute, the U.S. Department of Energy and Cornell University, obtained access to the blood of a patient with congenital heart disease who was treated extensively, but unsuccessfully, with several antibiotics including vancomycin. The team isolated the bacteria from the blood, and then used the whole-genome “shotgun” sequencing method to work out the entire genetic structure of S. aureus as it changed. They sequenced both the initial isolate and the later drug-resistant bacterium.

The comparison of the two sequences showed that the resistant bacterium carried 35 mutations in 33 places on its genome and also showed that the mutations showed up in the intermediate isolates in a sequential order in parallel with the gradually increasing resistance to vancomycin. Although initially sensitive to vancomycin, some of the bacteria were probably able to “hide” from the antibiotic in the tissue of the patient’s heart valve, Tomasz says. “The bacteria can bury themselves there and form a wall made of fibrin and platelets, and in that way, microbes in this abscess can selectively adapt to antibiotics in the bloodstream.”

The researchers discovered that as the bacteria acquired resistance to vancomycin, they also became resistant to a new antibiotic, daptomycin, which was thought to be able to treat multidrug-resistant S. aureus. “This is more than we bargained for,” Tomasz says. “The patient wasn’t even exposed to daptomycin, yet the bacteria acquired a resistance to it.” Further testing revealed that one of the mutated loci associated with decreasing vancomycin susceptibility resembled that found from isolates recovered in different regions of the world, raising hopes that these findings will indeed offer a representative model of resistant S. aureus, and may someday lead to new mechanisms for fighting drug-resistant staph.

Citation: Proceedings of the National Academy of Sciences 104(22): 9451-9456 (May 29, 2007)

Source: Rockefeller University

Explore further: Sensing distant tornadoes, birds flew the coop: Signs point to infrasound as nature's early warning system

add to favorites email to friend print save as pdf

Related Stories

Observers slam 'lackluster' Lima climate deal

3 minutes ago

A carbon-curbing deal struck in Lima on Sunday was a watered-down compromise where national intransigence threatened the goal of a pact to save Earth's climate system, green groups said.

Your info has been hacked. Now what do you do?

14 minutes ago

Criminals stole personal information from tens of millions of Americans in data breaches this past year. Of those affected, one in three may become victims of identity theft, according to research firm Javelin. ...

New Bond script stolen in Sony hack

17 minutes ago

An "early version" of the screenplay for the new James Bond film was the latest victim of a massive hacking attack on Sony Pictures Entertainment, its producers said in a statement on their website Sunday.

Ag-tech could change how the world eats

5 hours ago

Investors and entrepreneurs behind some of the world's newest industries have started to put their money and tech talents into farming - the world's oldest industry - with an audacious agenda: to make sure there is enough ...

World's rarest cetacean threatened by illegal gillnets

6 hours ago

The world's rarest cetacean could disappear in less than four years unless immediate action is taken by the Mexican government to protect it from entanglement in gillnets deployed illegally in its Gulf of California refuge, ...

Recommended for you

Warming leads to more run-ins with polar bears

2 hours ago

Word spread quickly: a polar bear, then two, were spotted near this remote Inuit village on the shores of Hudson Bay, about 1,800 kilometers (1,120 miles) north of Montreal.

Japanese scientist resigns over stem cell scandal

3 hours ago

A researcher embroiled in a fabrication scandal that has rocked Japan's scientific establishment said Friday she would resign after failing to reproduce results of what was once billed as a ground-breaking study on ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.