MCR-1 has been identified in the United States–what is it, and what does it mean?

                      E. coli, from Wikipedia commons

We’ve been expecting it, and now it’s here.

Yesterday, two article were released showing that MCR-1, the plasmid-associated gene that provides resistance to the antibiotic colistin, has been found in the United States. And not just in one place, but in two distinct cases: a woman with a urinary tract infection (UTI) in Pennsylvania, reported in the journal Antimicrobial Agents and Chemotherapy, and a positive sample taken from a pig’s intestine as part of the National Antimicrobial Resistance Monitoring System (NARMS), which tracks resistant bacteria related to retail meat products. Not surprising, not unexpected, but still, not good.

Colistin is an old antibiotic. Dating back to the 1950s, it’s been used sparingly over the decades because it can cause serious damage to the kidneys and nervous system. It’s also typically administered intravenously in humans, so you can’t just pop a colistin pill and be sent home from the doctor. Newer preparations appear to be safer, and because of the problem with antibiotic resistance in general and limited treatment options for multidrug-resistant Gram-negative infections in particular, colistin has seen a new life in the last decade or so as a last line of defense against some of these almost-untreatable infections.

Because of its sparing use in humans, resistance has not been much of an issue until recently. And while human use is relatively rare compared to other types of antibiotics, in animals, the story is different. Because colistin is old and cheap, it’s used as an additive to feed in Chinese livestock, to make them grow faster and fatter. (We do this here in the U.S. too, but using different antibiotics than colistin). So as would be expected, use of this antibiotic led to the evolution and spread of a resistant strain, due to the presence of the MCR-1 gene. By the first time they saw this resistance, it was already present in 20% of the pigs they tested near Shanghai, and 15% of the raw meat samples they tested. In this case, the gene is on a plasmid, which makes it easier to spread to other types of bacteria. To date, most of the reports of MCR-1 have been in E. coli, but it’s also been found in Salmonella and Klebsiella pneunoniae–all gut bacteria that can be spread from animals via contaminated food products, or person-to-person when someone carrying the bacterium doesn’t wash their hands after using the bathroom.

So a question becomes, how exactly did it get here? And that’s very difficult to say right now. The hospital where the human case was reported notes that the patient reported no travel history in the past 5 months (so it’s unlikely that she traveled to China, for instance, and picked up the gene or bacterium carrying it there). The hospital says they’ve not found other MCR-1 positive isolates from other patients, but also that they’ve only been testing specimens for 3 weeks, so…yeah. Hard to say. People and animals (like the tested pig) can carry E. coli or other species that harbor MCR-1 in their gut without becoming ill, so it may have been in the population for awhile (as they’ve seen in Brazil) before it came to the attention of medical researchers. Perhaps it’s been circulating in some of our meat products, or spreading in a chain of miniscule transfers of shit from person to person to person to person, for longer than we realize. Or both.

I was asked on Twitter yesterday, “Should I panic today or put that off until next week?” I’m not an advocate of panic myself, but I do think this is yet another concern and another hit on our antibiotic arsenal. It’s not widespread in this country and as mentioned, colistin is luckily not a first-line drug, so it won’t affect all *that* many people–for now, at least.

But.

There are already papers out there showing bacteria that have both NDM-1 (or related variants) and MCR-1 genes. NDM-1 is a gene that provides resistance to another class of last-resort antibiotics, the carbapenems. (Maryn McKenna has covered this extensively on her blog). When carbapenems fail, treatment with colistin sometimes works. But if the bacterium is resistant to both colistin and carbapenems, well…not good. That hasn’t been reported yet in the U.S., but it’s only a matter of time, as McKenna notes.

It doesn’t mean that we’re out of antibiotics (yet) or that everyone who has one of these resistant infections will be unable to find a treatment that works (yet). But we’re inching ever closer to those days, one resistant bacterium at a time.

Is there such a thing as an “evolution-proof” drug?

Eleven years ago, two scientists made a bet. One scientist wagered that a new type of antimicrobial agent, called antimicrobial peptides, would not elicit resistance from bacterial populations which were treated with the drugs. Antimicrobial peptides are short proteins (typically 15-50 amino acids in length) that are often positively charged. They are also a part of our body’s own innate immune system, and present in other species from bacteria to plants. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell, often by poking holes in them. Sometimes they work with the host to ramp up the immune response and overwhelm the invading microbe. Because the peptides are frequently targeted at the bacterial cell wall structure, it was thought that resistance to these drugs would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria.

Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so some reasoning went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in Staphylococcus aureus and Salmonella species, but we didn’t *witness* that resistance develop–therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.

The doubter of resistance, and the bet instigator, was Michael Zasloff of Georgetown University, who wrote in a 2002 review of antimicrobial peptides:

Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.

Certainly in the short term, resistance may be unlikely to evolve for reasons described above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides “improbable,” Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they published their results in Proceedings of the Royal Society

The result?

Zasloff had egg on his face. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.

Well, everything old is new again. A very similar claim has been making the rounds recently, originating from the press release for a new paper claiming to have found bacteria’s “Achilles’ heel,” advancing the claim that “Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future.”  A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here.

Student Guest Post: Arsenic, Benzene, and Now Clostridium? Smokers are Inhaling More Than Just Chemicals in Their Cigarettes

It’s time for this year’s second installment of student guest posts for my class on infectious causes of chronic disease. Second one this round is by Jonathan Yuska. 

If you happen to be one of the 46 million individuals who have not been swayed to quit smoking by the countless anti-cigarette ads in print and on television, here is one more piece of evidence that may have you second thinking that next puff. On top of the more than 3,000 chemicals and heavy metals already identified in ordinary cigarettes1, upwards of a million microorganisms per cigarette have also been found to live and thrive in virtually all cigarettes in the United States2. Microbes such as Bacillus (which is linked to the notorious anthrax disease), Clostridium, and Pseudomonas—to name a few—likely contaminate the tobacco leaves early at the farm level and are able to flourish during curing and manufacturing to be viable in the cigarette at the time of the consumer’s use. While some of the bacteria are capable of causing no more than a stomachache, others (and their respective endotoxins) have been linked to pneumonia and chronic lung inflammation—a widely recognized risk factor for cancer1,2. While cigarette smoking is a well-established cause of cancer in and of itself, the role microorganisms have in the toxicity of cigarette smoke should not go underplayed. With increasing evidence supporting the vast illness causing biodiversity found in cigarettes, hopefully more individuals will be aware of the dangerous contaminants they are welcoming into their bodies and call for greater sanitary measures to be taken to potentially create a less harmful cigarette product.

Approximately 23 different species of bacteria have been found in cigarette tobacco, many of which have been linked to serious illness in humans. For example, Pseudomonas aeruginosawhich is the leading cause of nosocomial pneumonia and often found in soil or sand—was found to be present in nearly all cigarettes tested in a study that looked at the presence of cigarette bacteria in the most commonly smoked brands, like Marlboro2. Another study interested in understanding the cause of severe lung inflammation in United States troops during Operation Iraqi Freedom found eight different species of Bacillus (five of which were never seen before) contaminating the soldier’s cigarettes3. Regardless of the actual bacteria within the cigarettes, the endotoxins derived from the bacteria that remain well after the bacteria have died have been shown to be a powerful inducer of lung inflammation (chronic inflammation is recognized as a powerful risk factor for cancer). It is theorized that the bacteria and their respective endotoxins may have an additive or multiplicative effect with tobacco smoke’s natural ability to cause pulmonary inflammation, though the amount of the effect that can be attributed is still up to debate2.

Research has shown that more than 90 percent of cigarettes are contaminated with some form of bacteria, and these bacteria are believed to originate early in the cigarette manufacturing process1. Similar to other crop cultivation, tobacco is grown in large fields where animal manure is used to provide the nutrients needed for a hearty crop. Some of the bacteria from the manure are believed to adhere to the tobacco leaves during the plant’s development. Curing the tobacco, which is essential in the cigarette manufacturing process to develop an ignitable, flavorful product, further facilitates bacterial growth because it is often done in moist, warm conditions3. Unlike other agriculture crops grown for consumption, tobacco has no regulations associated with its sanitation, and as a result, tobacco products can contain soil residues and insecticides in addition to a vast array of deleterious bacteria. Efforts to sanitize tobacco through an antimicrobial wash have been proven to be effective in reducing contaminants; however, since so little mainstream attention has been given to microbes in cigarettes, no sanitation process is currently being used by the cigarette industry2.

Misperceptions about how much risk the bacteria pose to the smoker is one reason so little attention has been given to microbes in cigarettes.  Some critics believe that bacteria in cigarettes pose no harm because the cigarette flakes are prevented from entering the lungs because of the built-in filter within the cigarette. Some further argue that the viable bacteria found in the tobacco are destroyed or heavily reduced in number by the heat of the cigarette. Though, the validity of these observations are derailed by the fact in the process of transportation, or even minor jostling, tobacco flakes are often seen lying freely on the mouth end of the filter. Thus, loose tobacco on filters could transfer bacteria to the mouths and lungs of smokers before the cigarette is even lit. Additionally, some extremely fine tobacco microparticulates are able to pass through the cigarette filters currently being used and can be inhaled deep into the lungs to cause inflammation2,5. The harsh, high temperature conditions of cigarette smoking also does little in eliminating the bacteria that are able to produce robust heat resistant endospores such as the bacterial species Bacillus and Clostridium1. It is clear that more attention should be given to dismiss the misperceptions of bacterial risk associated with cigarettes so that effective sanitary regulations can be applied to tobacco similar to other widely consumed foodstuffs.

If the more than 3,000 chemicals and heavy metals that have been identified in ordinary cigarettes have not influenced you to quit smoking, hopefully the realization that one cigarette can contain roughly 1,000,000 microorganisms will have you second thinking the habit the next time you light up. Microorganisms that have been linked to serious illness in humans like pneumonia and chronic inflammation are thought to contaminate tobacco leaves early in the manufacturing process, and these organisms thrive and multiply to be viable bacteria in the consumer cigarette. While cigarettes themselves are recognized as a serious cause of ill health, the role microorganisms have in their toxicity should not be underplayed. With a better understanding of the vast bacterial biodiversity within cigarettes, sanitary regulations that eliminate bacterial contamination should be mandated to potentially make a less harmful tobacco product. Though until then, people should recognize the dangerous bacterial contaminants they are welcoming into their bodies every time they light up.

Sources:

1.   Sapkota, Amy R., Sibel Berger, and Timothy M. Vogel. “Human Pathogens

Abundant in the Bacterial Metagenome of Cigarettes.” National Center for Biotechnology Information. 22 Oct. 2009. U.S. National Library of Medicine. 13 Apr. 2013 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854762/>.

2.  Pauly, J. L., J. D. Waight, and G. M. Paszkiewicz. “Tobacco flakes on cigarette filters

grow bacteria: A potential health risk to the smoker?” Tobacco Control. 18 Oct. 2007. 13 Apr. 2013 <http://tobaccocontrol.bmj.com/content/17/Suppl_1/i49.long>.

3. Rooney, Alejandro P., James L. Swezey, Donald T. Wicklow, and Matthew J. McAtee.

“Bacterial Species Diversity in Cigarettes Linked to an Investigation of Severe Pneumonitis in U.S. Military Personnel Deployed in Operation Iraqi Freedom.” Current Microbiology 51 (2005): 46-52.

4. “How to Grow Tobacco.” How To Grow Stuff. 23 Nov. 2007. 13 Apr. 2013

<http://www.howtogrowstuff.com/how-to-grow-tobacco/>.

5. Pauly, John L., and Geraldine Paszkiewicz. “Cigarette Smoke, Bacteria, Mold,

Microbial Toxins, and Chronic Lung Inflammation.” National Center for Biotechnology Information. 09 July 2011. U.S. National Library of Medicine. 13 Apr. 2013 <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136185/>.

 

 

Treatment of Chronic Otitis Media: Guidelines versus Practice

First of five student guest posts by Kristen Coleman

Every morning as I prepare for class, I go through the same internal dialogue, “to wear or not to wear my hearing aide.” I am forced to do this because when I was a child I, like most American children (about 80% by age 3 as estimated by the American Academy of Family Practitioners, AAFP), suffered from otitis media and my treatment resulted in hearing loss. The treatment I underwent was called tympanostomy with ventilation tube insertion, which has rapidly become the most common reason for general anesthesia in children in the United States. However, the AAFP reports that meta-analysis of studies exploring the effectiveness of this procedure indicate that benefit is only marginal at best. So why is it that our children are being exposed to this potentially quality of life altering procedure, if there is little benefit? In order to explore the reasons, we must delve further into the disease in question.

Previously, it had been commonly thought that chronic otitis media was characterized by a virus-laden sterile effusion behind the ear drum; meaning that bacteria were not thought to be present and thus, antibiotic therapy was not indicated. Now we know that chronic otitis media is most commonly due to infection of the middle ear by Streptococcus pneumoniae, Haemophilus influenza, Moraxella catarrhalis, (all of which are bacteria) or respiratory viruses. The organisms contribute to the buildup of fluid and pus behind the ear drum that is characteristic of this disease. Dr. Kim Stol and collaborators have reported findings that demonstrate that immune inflammatory response, measured through the presence of immune mediators called cytokines, may play a role in the damage to the ear during bacterial infection that commonly results in hearing loss or diminishment. As demonstrated by the research of Dr. Lusk of the University of Iowa, this immune-mediated damage can persist even after surgical intervention if bacteria persist in the middle ear, making medical management of the bacteria through antibiotic therapy even more essential.

Due to this evidence, the AAFP and other leading organizations that publish guidelines for treatment recommend antibiotic therapy as the gold standard of care for children suffering from chronic otitis media. These guidelines indicate rigorous treatment with high doses of antibiotics such as amoxicillin/clavulanate, cephalosporins and macrolides. If these antibiotics do not offer relief, clindamycin and tympanocentesis (removal of fluid from behind the ear drum with a needle) are then warranted. It is only when all of these medical treatments fail that tympanostomy tubes may be an appropriate option. However, it has been reported by researchers at Mount Sinai School of Medicine in New York City that of the 682 children who received tympanostomy tubes as treatment for chronic otitis media in their study in 2002, only 7.5% did so in accordance to the guidelines set forth by these organizations, and that most of these operations occurred before adequate attempts at antibiotic management of the disease could be utilized. In the study performed by Dr. Stol, it was reported that of the 116 participants in the study who were suffering from chronic otitis media, only 6.9% had received a recent antibiotic prescription, despite the fact that 53% of these patients were suffering from a bacterial form of the disease that may have responded favorably to antibiotic therapy.

As for me and my story, I had an initial round of ventilation tubes places in my ear drums when I was 6 years old, along with an adenoidectomy which was thought to help diminish my ear infections. My family was told that my disease was due to a virus and I was not prescribed any antibiotics prior to my surgical procedure. These tubes fell out the next year, and my chronic otitis media still had not resolved. More permanent tubes were placed in my ears at age 8 and these became lodged in my ear drums until college, all the while I suffered from chronic fluid and pain in my ears. When I had the tubes removed at age 19, my ear drums were permanently scarred and I had to undergo a bilateral tympanoplasty in which a surgeon tried to patch the holes in my ear drums, to no avail. All of this resulted in me having to wear a hearing aide in order to hear adequately at the age of 28.

As the report from Mount Sinai Medical School indicates, the discrepancy between practice and guidelines, as well as the overuse of surgical management in lieu of less-invasive medical management cannot be in the best interest of the children suffering from this disease, and steps need to be taken in order to educate physicians and families alike as to the most appropriate steps for treatment of this chronic disease in order to save our children from having stories like mine.

References:

1. Stol, Kim et al. Inflammation in the Middle Ear of Children with Recurrent or Chronic Otitis Media is Associated with Bacterial Load. The Pediatric Infectious Disease Journal. Volume 31, Number 11, pages 1128-1134. November 2012.

2. Lusk, Rodney P. et al. Medical Management of Chronic Suppurative Otitis Media Without Cholesteatoma in Children. Layngoscope: February 1986.

3. Keyhani, et al. Overuse of tympanostomy tubes in New York metropolitan area: evidence from five hospital cohort. Mount Sinai Medical School. BMJ: 2008.

4. American Association of Family Practitioners. www.aafp.org/afp/2007/1201/p1650.html

Using zombies to teach science

With my colleague Greg Tinkler, I spent an afternoon last week at a local public library talking to kids about zombies:

The Zombie Apocalypse is coming. Will you be ready? University of Iowa epidemiologist Dr. Tara Smith will talk about how a zombie virus might spread and how you can prepare. Get a list of emergency supplies to go home and build your own zombie kit, just in case. Find out what to do when the zombies come from neuroscientist Dr. Greg Tinkler. As a last resort, if you can’t beat them, join them. Disguise yourself as a zombie and chow down on brrraaaaiiins, then go home and freak out your parents.

Why zombies? Obviously they’re a hot topic right now, particularly with the ascendance of The Walking Dead. They’re all over ComicCon. There are many different versions so the “rules” regarding zombies are flexible, and they can be used to teach all different kinds of scientific concepts–and more importantly, to teach kids how to *think* about translating some of this knowledge into practice (avoiding a zombie pandemic, surviving one, etc.) We ended up with about 30 people there: about 25 kids (using the term loosely, they ranged in age from maybe age 10 to 18 or so) and a smattering of adults. I covered the basics of disease transmission, then discussed how it applied to a potential “zombie germ,” while Greg explained how understanding the neurobiology of zombies can aid in fleeing from or killing them. The kids were involved, asked great questions, and even taught both of us a thing or two (and gave us additional zombie book recommendations!)

For infectious diseases, there are all kinds of literature-backed scenarios that can get kids discussing germs and epidemiology. People can die and reanimate as zombies, or they can just turn into infected “rage monsters” who try to eat you without actually dying first. They can have an extensive incubation period, or they can zombify almost immediately. Each situation calls for different types of responses–while the “living” zombies may be able to be killed in a number of different ways, for example, reanimated zombies typically can only be stopped by destroying the brains. Discussing these situations allows the kids to use critical thinking skills, to plan attacks and think through choice of weapons, escape routes and vehicles, and consider what they might need in a survival kit.

Likewise, zombie microbes can be spread through biting, through blood, through the air, by fomites or water, even by mosquitoes in some books. Agents can be viral, bacterial, fungal, prions or parasitic insect larvae (or combinations of those). Mulling on these different types of transmission issues and asking simple questions:

“How would you protect yourself if infection was spread through the air versus only spread by biting?”

“How well would isolation of infected people work if the incubation period is very long versus very short?”

“Why might you want to thoroughly wash your zombie-killing arrows before using them to kill squirrels, which you will then eat?” (ahem, Daryl)

can open up avenues of discussion into scientific issues that the kids don’t even realize they’re talking about (pandemic preparedness, for one). And the great thing is that these kids are *already experts* on the subject matter. They don’t have to learn about the epidemiology of a particular microbe to understand disease transmission and prevention, because they already know more than most of the adults do on the epidemiology of zombie diseases–the key is to get them to use that knowledge and broaden their thinking into various “what if” situations that they’re able to talk out and put pieces together.

It can be scary going to talk to kids. Since this was a new program, we didn’t know if anyone would even show up, or how it would go over. Greg brought a watermelon for some weapons demonstrations (household tools only–a screwdriver, hammer and a crowbar, no guns or Samurai swords) which was a big hit. Still, I realize many scientists are more comfortable talking with their peers than with 13-year-olds. Talking about something a bit ridiculous, like an impending zombie apocalypse, can lessen anxiety because it takes quite a lot of effort to be boring with that type of subject matter; it’s entertaining; and kids will listen. And after all, what you don’t know, might eat you.

Hemolytic uremic syndrome (HUS) in history–part 2

As I mentioned yesterday, the epidemiology of hemolytic uremic syndrome (HUS) was murky for several decades after it was first defined in the literature in 1955. In the ensuing decades, HUS was associated with a number of infectious agents, leading to the general belief that it was a “multifactorial disease”–one that had components of genetics and environment, much like we think of multiple sclerosis today, for example.

Several HUS outbreaks made people think twice about that assumption, and look deeper into a potential infectious cause. A 1966 paper documented the first identified outbreak of HUS, which occurred in Wales. The researchers examined a number of possible environmental factors the patients may have had in common–including food, water, and various toxins–but came up empty. They sum up:

Since it is almost invariably preceded by a gastrointestinal or respiratory illness, it seems probable that it represents a response to an infection. Although Gianantonio et al. (1964) have identified one possible causative virus, it may be that various infective agents can initiate the syndrome.

This idea held throughout the next 20-odd years, as numerous studies looked at both environmental and genetic effects that may be leading to HUS. A 1975 paper examined HUS in families, suggesting that there may be two types of HUS (which we now know to be true–the genetic form is less often associated with diarrhea, and tends to have a worse prognosis as I mentioned yesterday). But still, no definitive cause for either.

There were also a number of studies testing individuals for many different types of pathogens. A 1974 paper enrolled patients in the Netherlands between 1965 and 1970, but one of the inclusion criteria was a “history of a prodromal illness in which gastrointestinal or respiratory tract symptoms were present.” The respiratory tract symptoms are mentioned in a number of papers, and were probably a red herring that sent people in search of the wrong pathogens for awhile. In this particular paper, they examined children for infection with a number of viral and bacterial pathogens, using either culture or serological methods (looking for antibodies which may suggest a recent infection). In that portion of the paper, they note a possible association with adenoviruses, but state that the data don’t support a bacterial infection–a viral etiology was deemed more likely. Regarding basic epidemiology, they did note a few small clusters of cases in families or villages, as well as a peak in cases in spring/summer–as well as an increasing number of cases from the first year of their study to the last. The epidemiology of HUS was starting to become clearer, and the syndrome appeared to be on the rise.

Even as additional case reports occasionally targeted foods as a precursor to HUS outbreaks, it wasn’t until the late 1970s and early 1980s that HUS really started to come into focus. In 1977, a paper was published identifying the “Vero toxin”–a product of E. coli that caused cytotoxicity in Vero cells (a line of African green monkey kidney cells, commonly used in research). Researchers were closing in.

When is MRSA not MRSA?

…when it contains a weird gene conferring methicillin resistance that many tests miss.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a big issue in the past 15 years or so, as it turned up outside of its old haunts (typically hospitals and other medical facilities) and started causing infections–sometimes very serious–in people who haven’t been in a hospital before. Typically MRSA is diagnosed using basic old-school microbiology techniques: growing the bacteria on an agar plate, and then testing to see what antibiotics it’s resistant to. This can be done in a number of ways–sometimes you can put a little paper disc containing antibiotics right onto a plate where you’ve already spread out a bacterial solution and see which discs inhibit growth, or sometimes you can grow the bacteria in a plate with increasing concentrations of antibiotics, to see when the drugs are high enough to stop growth. Both look at the phenotype of these bacteria–the proteins they’re expressing which lead to the bacteria’s drug resistance.

However, these culture-based methods are slow–they can take days between when the patient first is seen by a doctor and the time the results come back from the clinical lab. For this reason, increasingly labs are moving to molecular methods, which are much quicker than the culture-based methods. Indeed, detection of the gene responsible for methicillin resistance, mecA, has been the gold standard for *really* identifying MRSA, even beyond phenotypic methods.

A new pair of papers demonstrate the limitations of this reliance. Like many science discoveries, this one started with a “huh, weird” moment. Investigators noticed that a number of their S. aureus samples were categorized as MRSA using the traditional phenotypic methods, but were negative when it came to the mecA DNA test. Genetic analysis showed that these isolates carried a different mecA gene, dubbed mecALGA251. The investigators searched their isolate collection in England, and also worked with collaborators in Scotland and Denmark to search through their banks for additional mecA-negative MRSA, and found almost 70 isolates, including one dating back to 1975. (A second paper by a different group examined two isolates in Ireland).

Now is when it starts to get really interesting. (Continued below)
Continue reading “When is MRSA not MRSA?”