Tag: superbug

‘Nose-y’ Bacteria Could Yield A New Antibiotic to Fight Drug-Resistant SuperBugs: lugdunin

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Once scientists grew these Staphylococcus lugdunensis bacteria in a lab dish, they were able to isolate a compound that’s lethal to another strain commonly found in the nose that can make us sick — Staphylococcus aureus.

by Carolyn Beans

With antibiotic-resistant super bugs on the rise, researchers are on an urgent hunt for other bacteria that might yield chemicals we can harness as powerful drugs. Scientists once found most of these helpful bacteria in soil, but in recent decades this go-to search location hasn’t delivered.

Now, researchers at the University of Tübingen in Germany say that to find at least one promising candidate, we need look no further than our own noses.

The scientists report Wednesday in the journal Nature that a species of bacteria inside the human nose produces a substance capable of killing a range of bacteria, including the strain of drug-resistant Staphylococcus aureus known as MRSA.

The Tübingen team is delighted with their find. “It was totally unexpected,” says study author Andreas Peschel.

The scientists already knew that S. aureus lives in the noses of about 30 percent of humans, usually without causing harm — most people never know they are carriers of the bacterium. But if the body becomes compromised (whether by surgery, physical trauma, an underlying illness or suppressed immune system) the little cache of S. aureus in the nose can suddenly launch an attack against its human host. And if the strain of bacteria is MRSA, that infection can be lethal.

The scientists wondered how 70 percent of human noses are able to avoid harboring S. aureus. They guessed it might have something to do with neighboring bacteria.

So the researchers pitted 90 different human nasal bacteria in one-on-one battles with S. aureus in the lab. Indeed, one of these bacteria — Staphylococcus lugdunensis — prevented the dangerous pathogen from growing.

They then studied the arsenal of chemicals that S. lugdunensis produces until they found one that stops S. aureus in its tracks – a new antibiotic that they named lugdunin.

Follow-up work confirmed that lugdunin can treat S. aureus skin infections in mice, and limit the spread of S. aureus in a rat’s nose.

Lugdunin may already be keeping S. aureus out of our noses. In a group of 187 hospitalized people, the same scientists found S. aureus in the noses of just 5.9 percent of people who also harbored the lugdunin-producing bacteria, but 34.7 percent of those who didn’t.

Other recent studies have shown that bacteria living in humans carry genes that have the potential to make antibiotics. The Tübingen study takes those results a step further by showing that an antibiotic produced by a bacterium in the human nose can successfully treat an animal’s infection.

“This paper is a really nice follow-up,” says Dr. Nita Salzman, a pathologist at the Medical College of Wisconsin. “It’s a sort of proof of principle that the microbiome is a good source for novel antibiotics.”

The researchers have applied for a patent for lugdunin, but say that the prototype antibiotic is still many years away from being ready to treat humans.

The really important contribution of this study is not lugdunin itself, says microbiologist Kim Lewis of Northeastern University, but rather the new approach for finding antibiotic-producing bacteria within our own bodies.

“The reason we ran out of antibiotics in the first place is because most of them came from soil bacteria and they make up 1 percent of the total [bacterial] diversity,” Lewis says.

Scientists kept searching in soil, he says, because they already had some success there and know that soil bacteria are exceptionally good at producing antibiotics.

But now it’s time to look within us. And the team in Tübingen has only just begun their hunt.

“We have started a larger screening program and we’re sure there will be many additional antibiotics that can be discovered,” says Peschel.

http://www.npr.org/sections/health-shots/2016/07/27/487529338/nose-y-bacteria-could-yield-a-new-way-to-fight-infection

That New Superbug Was Found in a UTI and That’s Key

On By A.P.In Medicine1 Comment
BR3GWM bacteria streaked and grows on an agar plate in the lab
BR3GWM bacteria streaked and grows on an agar plate in the lab

by SARAH ZHANG

THE WOMAN HARBORING E. coli resistant to colistin did not know it, and it’s only luck that we do. Her doctor would have never prescribed that last-resort antibiotic for a routine urinary tract infection—it can cause serious kidney damage. But her doctor did take a urine sample, which ended up at the Walter Reed National Military Medical Center, where researchers had recently started testing for colistin resistance. The test came back positive. Then the came scary headlines about a new superbug in the US.

Superbugs are bacteria with genetic mutations that let them survive humanity’s harshest weapons in germ warfare: antibiotics. The gene behind this E. coli’s colistin resistance is called mcr-1. It first emerged last year when Chinese researchers found it in samples from hospital patients and raw pork. Why pork? Colistin’s serious side effects mean it’s no longer used as a human antibiotic in many countries. But in China, farmers have been adding it by the pound into feed to fatten animals up.

Once epidemiologists knew to look for mcr-1, they found it in Malaysia, England and then the rest of Europe. It was only a matter of time before colistin resistance turned up in the US. On the same day news came out about this woman’s colistin-resistant UTI, the Department of Health and Human Services also announced it found mcr-1 in a sample from a pig intestine.

Colistin is not used in animal feed in the US, so it’s unclear how colistin-resistant bacteria ended up infecting that woman—or that pig. But food and people move freely across borders. And more even seriously, US animal farmers do use other antibiotics—even human ones—on chicken, pigs, and cows. A growing body of research has linked antibiotic use in food animals to drug-resistant bouts of food poisoning from salmonella, campylobacter, and MRSA. Even more interesting is a possible link between antibiotics on meat and urinary tract infections, which science journalist Maryn McKenna has covered extensively. The Food and Drug Administration issued a guidance last year for farms to phase out medically important antibiotics, though only voluntarily.


The Rise of the Drug-Resistant UTI
Urinary tract infections are damn common—annoyingly common if you ask many women. And antibiotic resistant UTIs are on the rise, too: From 2000 to 2010, the number of UTIs resistant to the antibiotic Cipro went from 3 percent to 17.1 percent. Because UTIs afflict so many people, they’re fairly representative antibiotic resistance out there in people community—especially compared to the resistant infections that epidemiologists tend to study most intensely, like ones that kill already sick hospital patients. “UTIs are a good picture of what people are being exposed to on a daily basis” says Amee Manges, an epidemiologist at the University of British Columbia. Case in point: That colistin-resistant bacteria in the woman from Philadelphia.

Manges has spent the past fifteen years studying the link between antibiotic use in meat production, especially poultry, and UTIs. Back when she was working on her doctoral thesis at the University of California, Berkeley, she kept seeing young, otherwise healthy students with UTIs. Originally, she thought she was going to track sexual transmission of the E. coli that caused such infections. With that kind of sporadic sexual transmission, she should have seen many different strains. But when she DNA fingerprinted the bacteria, she found they were all the same strain—the same pattern you’d see from a single source, like if the campus cafeteria gave everyone food poisoning. She was never able to trace those UTI cases back to the original source, but she’s been working on the question ever since.

UTIs are so hard to trace because the infection might not set in until long after a patient first acquired to bacteria. Say a woman eats some undercooked chicken. “The bacteria just hangs out in your intestine for months or possibly years,” says Manges. Then you get risk factor for UTI—sex or a catheter insertion—and that bacteria makes its way from, ahem, the end of your gut to the urethra. But getting people to remember what they ate a week ago is hard. Getting people to remember what they ate a year ago? Hahaha.

The Surveillance Net
Nevertheless, Manges and others have found that strains on meat match strains found in UTIs. Because of the difficulty in tracing UTIs, that evidence is not as ironclad as the evidence for antibiotics use and antibiotic-resistant food poisoning. With routine surveillance of UTIs though, epidemiologists could get a better handle of not only resistant bacteria that come from meat—but also other sources like drinking water or travel or family members being in the hospital. But that surveillance doesn’t happen. “There’s no organized infrastructure to get a good handle about resistance rates across communities,” says Kalpana Gupta, an infectious disease specialist at Boston University.

When patients walk in with UTIs, doctors will often hand out antibiotics without doing a urine culture. Growing the bacteria takes two days—testing for antibiotic-resistance a third—and by that time the patient is usually on the mend already. The fact that the women in Philadelphia got tested was unusual. The fact that her sample was tested against colistin even more so. As Gupta says, “Colistin is not something we would even use to treat UTIs.” (Resistance to another class of antibiotics triggered that extra test in this case.)

The Centers for Disease Control and Prevention is now following up with the woman in Philadelphia to find out she ended up with that colistin-strain of E. coli, which has never been found in the US before. Her infection was fortunately not resistant to all antibiotics. But what makes the colistin-resistance gene mcr-1 so worrisome is that it’s on a small loop of DNA that different bacteria easily swap back and forth. Someday, another bacteria already immune to all other antibiotics will pick up mcr-1, too. It’s only a matter of time.

The wider the surveillance net though, the more quickly we’ll find it.

Art informing science: possible medieval remedy for modern day superbugs?

On By A.P.In Art, MedicineLeave a comment

A one thousand year old Anglo-Saxon remedy for eye infections which originates from a manuscript in the British Library has been found to kill the modern-day superbug MRSA in an unusual research collaboration at The University of Nottingham.

Dr Christina Lee, an Anglo-Saxon expert from the School of English has enlisted the help of microbiologists from University’s Centre for Biomolecular Sciences to recreate a 10th century potion for eye infections from Bald’s Leechbook an Old English leatherbound volume in the British Library, to see if it really works as an antibacterial remedy. The Leechbook is widely thought of as one of the earliest known medical textbooks and contains Anglo-Saxon medical advice and recipes for medicines, salves and treatments.

Early results on the ‘potion’, tested in vitro at Nottingham and backed up by mouse model tests at a university in the United States, are, in the words of the US collaborator, “astonishing”. The solution has had remarkable effects on Methicillin-resistant Staphylococcus aureus (MRSA) which is one of the most antibiotic-resistant bugs costing modern health services billions.

The team now has good, replicated data showing that Bald’s eye salve kills up to 90% of MRSA bacteria in ‘in vivo’ wound biopsies from mouse models. They believe the bactericidal effect of the recipe is not due to a single ingredient but the combination used and brewing methods/container material used. Further research is planned to investigate how and why this works.

The testing of the ancient remedy was the idea of Dr Christina Lee, Associate Professor in Viking Studies and member of the University’s Institute for Medieval Research. Dr Lee translated the recipe from a transcript of the original Old English manuscript in the British Library.

The recipe calls for two species of Allium (garlic and onion or leek), wine and oxgall (bile from a cow’s stomach). It describes a very specific method of making the topical solution including the use of a brass vessel to brew it in, a straining to purify it and an instruction to leave the mixture for nine days before use.

The scientists at Nottingham made four separate batches of the remedy using fresh ingredients each time, as well as a control treatment using the same quantity of distilled water and brass sheet to mimic the brewing container but without the vegetable compounds.

The remedy was tested on cultures of the commonly found and hard to treat bacteria, Staphylococcus aureus, in both synthetic wounds and in infected wounds in mice.

The team made artificial wound infections by growing bacteria in plugs of collagen and then exposed them to each of the individual ingredients, or the full recipe. None of the individual ingredients alone had any measurable effect, but when combined according to the recipe the Staphylococcus populations were almost totally obliterated: about one bacterial cell in a thousand survived.

The team then went on to see what happened if they diluted the eye salve – as it is hard to know just how much of the medicine bacteria would be exposed to when applied to a real infection. They found that when the medicine is too dilute to kill Staphylococcus aureus, it interfered with bacterial cell-cell communication (quorum sensing). This is a key finding, because bacteria have to talk to each other to switch on the genes that allow them to damage infected tissues. Many microbiologists think that blocking this behaviour could be an alternative way of treating infection.

Dr Lee said: “We were genuinely astonished at the results of our experiments in the lab. We believe modern research into disease can benefit from past responses and knowledge, which is largely contained in non-scientific writings. But the potential of these texts to contribute to addressing the challenges cannot be understood without the combined expertise of both the arts and science.

“Medieval leech books and herbaria contain many remedies designed to treat what are clearly bacterial infections (weeping wounds/sores, eye and throat infections, skin conditions such as erysipelas, leprosy and chest infections). Given that these remedies were developed well before the modern understanding of germ theory, this poses two questions: How systematic was the development of these remedies? And how effective were these remedies against the likely causative species of bacteria? Answering these questions will greatly improve our understanding of medieval scholarship and medical empiricism, and may reveal new ways of treating serious bacterial infections that continue to cause illness and death.”

University microbiologist, Dr Freya Harrison has led the work in the laboratory at Nottingham with Dr Steve Diggle and Research Associate Dr Aled Roberts. She will present the findings at the Annual Conference of the Society for General Microbiology which starts on Monday 30th March 2015 in Birmingham.

Dr Harrison commented: “We thought that Bald’s eyesalve might show a small amount of antibiotic activity, because each of the ingredients has been shown by other researchers to have some effect on bacteria in the lab – copper and bile salts can kill bacteria, and the garlic family of plants make chemicals that interfere with the bacteria’s ability to damage infected tissues. But we were absolutely blown away by just how effective the combination of ingredients was. We tested it in difficult conditions too; we let our artificial ‘infections’ grow into dense, mature populations called ‘biofilms’, where the individual cells bunch together and make a sticky coating that makes it hard for antibiotics to reach them. But unlike many modern antibiotics, Bald’s eye salve has the power to breach these defences.”

Dr Steve Diggle added: “When we built this recipe in the lab I didn’t really expect it to actually do anything. When we found that it could actually disrupt and kill cells in S. aureus biofilms, I was genuinely amazed. Biofilms are naturally antibiotic resistant and difficult to treat so this was a great result. The fact that it works on an organism that it was apparently designed to treat (an infection of a stye in the eye) suggests that people were doing carefully planned experiments long before the scientific method was developed.”

Dr Kendra Rumbaugh carried out in vivo testing of the Bald’s remedy on MRSA infected skin wounds in mice at Texas Tech University in the United States. Dr Rumbaugh said: “We know that MRSA infected wounds are exceptionally difficult to treat in people and in mouse models. We have not tested a single antibiotic or experimental therapeutic that is completely effective; however, this ‘ancient remedy’ performed as good if not better than the conventional antibiotics we used.”

Dr Harrison concludes: “The rise of antibiotic resistance in pathogenic bacteria and the lack of new antimicrobials in the developmental pipeline are key challenges for human health. There is a pressing need to develop new strategies against pathogens because the cost of developing new antibiotics is high and eventual resistance is likely. This truly cross-disciplinary project explores a new approach to modern health care problems by testing whether medieval remedies contain ingredients which kill bacteria or interfere with their ability to cause infection”.

http://www.nottingham.ac.uk/news/pressreleases/2015/march/ancientbiotics—a-medieval-remedy-for-modern-day-superbugs.aspx