A strain of MRSA that humans can contract from livestock most likely became drug resistant due to the use of antibiotics on the farm. That's according to the authors of a study in mBio this week, who looked closely at the genetic relationships among strains of the antibiotic resistant bacterium MRSA (methicillin-resistant Staphylococcus aureus). They discovered that ST398, a type of MRSA found in livestock that can also be passed to humans was originally a human strain, and it developed resistance to antibiotics once it was picked up by farm animals. The finding illustrates a very close link between antibiotic use on the farm and potentially lethal human infections.
MRSA is the well-known cause of a variety of invasive skin infections that can quickly turn life-threatening, but in 2003, a novel form of MRSA called ST398 emerged in livestock. Today, ST398 regularly infects farm workers and others who come into contact with infected livestock with any of several types of acute infections, including skin and soft tissue infections, respiratory infections, and bacteremia (also called sepsis). The strain can now be found in pigs, turkeys, cattle, and other livestock and has been detected in 47% of meat samples in the U.S..
It has been thought that overuse of antibiotics in livestock production could be fueling antibiotic resistance in bacteria, including S. aureus. In 2001, the Union of Concerned Scientists estimated that livestock producers in the U.S. used 24.6 million pounds of antibiotics per year for non-therapeutic purposes, a controversial practice that has now been banned in the European Union. The mBio study draws a line between the exposure of S. aureus to antibiotics on farms and the development of a form of MRSA that can threaten human lives, a correlation that has long been suspected but has been difficult to study directly.
A team of researchers from the Translational Genomics Research Institute (TGen) in Flagstaff, Arizona, the Statens Serum Institut in Denmark, and several other institutions sequenced the genomes of 88 different S. aureus isolates that are all closely related to ST398 to determine the family relationships among antibiotic sensitive strains and antibiotic resistant strains from both humans and animals.
An analysis of the various genomes revealed that ST398 most likely evolved from an antibiotic-sensitive strain of S. aureus that came from humans. Once it found a home in livestock, the genome sequences indicate this strain changed rapidly, acquired some new genes, and differentiated into many different types, including ST398, which is resistant to a few different antibiotics.
"Most of the ancestral human strains were sensitive to antibiotics, whereas the livestock strains had acquired resistance on several independent occasions," says Ross Fitzgerald of the University of Edinburgh in Scotland, who reviewed the paper for mBio. This implies that the bacterium picked up the ability to fend off antibiotics after it migrated into livestock, says Fitzgerald.
The fact that ST398 originally came from a human is significant, says Fitzgerald, because it shows that infection is a two-way street. "Intensive farming practices could promote the transfer of bacteria between different host species including humans to animals," says Fitzgerald. ST398's family tree shows that sharing bacteria with livestock could well mean that those bacteria come back to us with the ability to defeat antibiotics.
02/21/2012
02/16/2012
02/09/2012
Urinary tract infections go from bad to worse: tracking E. coli on its march to the kidneys
Cranberry juice, anyone? Most everyone has had to deal with a urinary tract infection at some point, but as common as the condition is, we still know little about how bacteria progress through the urinary tract. Observations have taught that bacteria may move from the urethra, into the bladder, then up the ureters to the kidneys, leading to kidney infection, or, if the bacteria gain access to the bloodstream, to bacteremia.
In mBio this week, a new study takes a more detailed look at how E. coli, which is responsible for 80% of uncomplicated UTI cases, establishes itself and advances on its painful march to the kidneys.
Walters et al. infected mice with ten slightly different clones of E. coli and followed their progress through the urinary tract and into the bloodstream. Looking at the presence and relative abundances of the various strains in the urethra, bladder, ureter, kidneys, and spleen (which is only linked to the kidneys through the bloodstream and, hence, serves as an indicator of bacteremia), they discerned that different lineages dominated different sites at different times.
These observations run counter to a simplistic stepwise model in which one strain moves at the forefront of infection and establishes itself at each site along the way. Rather, kidney infection and bacteremia associated with UTI are apparently the result of multiple rounds of ascension and dissemination and not necessarily the expansion of a single clonal lineage. So bacteria ascend the urinary tract using their flagella, they're washed back down by the flow of urine, more ascend, more get washed down, etc., and what you have in the end is a complicated picture of how E. coli gets around and lingers in the various areas of the anatomy. Passage from the kidneys to the bloodstream, on the other hand, is a big bottleneck for E. coli.
The authors write that getting a grasp on the ins and outs of E. coli populations in the urinary tract is more than just an academic pursuit: knowing how different bacterial populations become dominant over time while others are lost could point the way to new therapeutics that target specific strategies E. coli uses for success in this habitat.
01/31/2012
Special Commentaries on NSABB and H5N1 Redactions: What do you think?
mBio is publishing a special series of Commentaries this week in response to recent actions of the U.S. National Science Advisory Board for Biosecurity (NSABB), which recommended that two scientific journals withhold crucial details of upcoming relating to a novel strain of the bird flu virus, H5N1. The Commentaries, written by prominent scientists (including the acting chair of the NSABB), weigh in on whether the recommendations were necessary and what role biosecurity considerations should play in the dissemination of research findings. Read the Commentaries and the accompanying editorial, then come back to the blog and use the "comments" function below to discuss your thoughts with other readers.
The strain of avian flu in question has caused hundreds of deaths worldwide, and though it is highly lethal in humans, it apparently lacks the ability to transmit easily from person to person. The current controversy surrounds experiments that created a form of the H5N1 virus that is transmissible from ferret to ferret, animals used as models of human flu infection.
In the interest of biosecurity, the NSABB recommended that the federal government move to restrict information in the study that would enable a reader to replicate the experiments that enhanced the transmissibility of the virus. The government honored the recommendation and asked the scholarly journals in question, Science and Nature, to redact many of the experimental details, an unprecedented request to which the researchers and journals agreed.
This recommendation has generated tremendous controversy among scientists, and the authors of the studies recently announced they will suspend their work for two months to allow the dust settle.
Here's how the Commentaries shake out:
• In the first Commentary, Paul Keim (acting chair of the NSABB) lays out his reasons for supporting these recommendations. According to Keim, the fact that it is possible for a highly virulent form of the bird flu virus to acquire the ability to transmit from mammal to mammal is the most important piece of information in the study and it should compel policy makers to move forward with greater urgency in developing flu-fighting infrastructure. The experimental details, on the other hand, would not enhance public health efforts and could actually enable those with ill intent to create a strain of flu that would put lives in danger.
• Robert Webster of St Jude Children’s Research Hospital in Memphis, asks how science and policy can maintain the sharing of scientific information while minimizing risks to public health. Webster argues there is an urgent need for general guidance in the matter and he proposes creating an international panel to consider approaches to promoting research while maintaining biosecurity.
• The final contributor, Vincent Racaniello of Columbia University, argues that NSABB was wrong to recommend suppressing the information in these studies. It is not known whether the ferret adapted virus is lethal or transmissible among humans, Racaniello says, and he points out that adapting viruses to living in lab animals is actually a common strategy for reducing their suitability and virulence to human hosts.
The matter of the NSABB and the H5N1 research raises important questions for science and policy, the answers to which principled persons may disagree. What do you think? Did the NSABB make the right call? Did the journals do the responsible thing or bow to pressure?
And what would you do if it were your research?
