Highly Drug Resistant, Virulent Strain of Pseudomonas aeruginosa Arises in Ohio

A team of clinician researchers has discovered a highly virulent, multidrug resistant form of the pathogen, Pseudomonas aeruginosa, in patient samples in Ohio. Their investigation suggests that the particular genetic element involved, which is still rare in the United States, has been spreading heretofore unnoticed, and that surveillance is urgently needed. The research is published ahead of print in Antimicrobial Agents and Chemotherapy.

The P. aeruginosa contained a gene for a drug resistant enzyme called a metallo beta-lactamase. Beta-lactamases enable broad-spectrum resistance to beta-lactam antibiotics, including carbapenems, cephalosporins, and penicillins, because they can break the four atom beta-lactam ring, a critical component of these antibiotics’ structure.
The initial isolate of metallo-beta-lactamase-producing P. aeruginosa was identified in March, 2012, in a foot wound of a 69-year-old man with type 2 diabetes living in a long-term care facility. During 2012-2013, the investigators identified this highly antibiotic-resistant infection in six other patients. One of the seven patients subsequently died of the infection.

The cases are linked epidemiologically via admission to a community hospital and residence in long-term care facilities in Northeast Ohio. The one exception was a patient from Qatar who was transferred into a tertiary medical center in Ohio, says lead author Federico Perez, of the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.

The investigators subsequently found that the metallo beta-lactamase was contained within an integron, a genetic element that can jump from one species of bacterium to another, can reside on plasmids or within the chromosomes, and is known for being able to contain multiple antibiotic resistance genes.

This particular metallo beta-lactamase, verona integron-encoded metallo beta-lactamse (VIM), is widespread globally, if not in the US. “VIM enzymes confer resistance to imipenem and all other beta-lactams,” says Perez. “They are not inhibited by metallo beta-lactamase inhibitors.”

“Alarmingly, the [extensively drug-resistant] phenotype expressed by some of these isolates precluded any reliable antibiotic treatment since they even displayed intermediate resistance to colistin, an ‘agent of last resort’,” the researchers write. “Patients who were affected had multiple comorbidities, endured prolonged colonization, required long-term care and, in one instance had a lethal outcome from a bloodstream infection.”

On top of everything else, genomic sequencing and assembly showed that the integron was part of a novel 35 kilobase region that included a transposon (another mobile genetic element) and the so-called Salmonella Genomic Island 2 (SGI2). That indicated that a recombination event had occurred between Salmonella and P. aeruginosa, contributing even more resistance genes to the latter.

“This is the first description of genetic exchange of a large mobile element—the Salmonella Genome Island—and resistance genes between P. aerugenosa and Salmonella, says Perez. “This movement of genetic material creates concern that metallo beta-lactamases will disseminate rapidly in these enteric pathogens that are also very invasive. We are also concerned about the possibility of enhanced virulence.”

The manuscript can be found online at http://bit.ly/asmtip0814a. The final version of the article is scheduled for the October 2014 issue of Antimicrobial Agents and Chemotherapy.


Comments

Post a Comment

Popular posts from this blog

Fussy eaters: the favoured food of Salmonella

Image
As antibiotic resistance increases the search for new anti-bacterial treatments becomes more and more important. One way to design anti-bacterials is to find specific biochemical pathways that the bacteria require to survive, and develop drugs that block off these pathways. Some pathways are better targets than others and for  Salmonella bacteria it was thought that pathways dealing with nutrient metabolises would be a lost cause. Salmonella lives in the intestine, which hosts a whole variety of different nutrients, so surely preventing the bacteria from using a specific one wouldn’t cause them much undue distress. It’s been found, however, that as they grow and spread in the inflamed intestine the bacteria are heavily reliant on one particular nutrient: fructose-asparagine. The chemical structure of fructose-asparagine, image from the reference. The importance of fructose-asparagine metabolism was originally discovered durin...
Read more

Timing is key for bacteria surviving antibiotics

For bacteria facing a dose of antibiotics, timing might be the key to evading destruction. In a series of experiments, Princeton researchers found that cells that repaired DNA damaged by antibiotics before resuming growth had a much better chance of surviving treatment. When antibiotics hit a population of bacteria, often a small fraction of "persister" cells survive to pose a threat of recurrent infection. Unlike bacteria with genetic resistance to antibiotics, evidence suggests that persisters stay alive in part by stalling cellular processes targeted by the drugs. In a new study, Princeton researchers examined a class of antibiotics that target bacterial DNA. In bacterial populations, some cells repair damaged DNA before resuming growth, and others resume growth before making repairs. The researchers found that those that make repairs before resuming growth generally are the ones that survive as persisters. The research advances a long-term goal to make ...
Read more

HIV lies dormant in brain?

Image
The HIV virus, which causes AIDS, has long been known to target and disable cells of the immune system, which are responsible for fighting off invading microorganisms and for suppressing malignant cancers. More recently, researchers also learned HIV not only targets immune cells in the bloodstream but also in the brain and spinal cord and that HIV can lie dormant in a person’s body for many years. My mentor, Dr. Habibeh Khoshbouei , has been working on this problem and learned that one consequence of HIV in the brain is that age-related diseases develop much earlier . This includes neurological conditions such as Alzheimer’s and Parkinson’s disease , as well as an increased susceptibility to drug addiction . Our lab wanted to learn why. HIV effects persist despite treatment HIV, the virus that causes AIDS, is shown budding out of an immune cell, which the virus infects and uses to replicate. NIH, via Wi...
Read more