Plants may be transmitting superbugs to people

Antibiotic-resistant infections are a threat to global public health, food safety and an economic burden. To prevent these infections, it is critical to understand how antibiotic-resistant bacteria and their genes are transmitted from both meat and plant-foods. Researchers have now shown how plant-foods serve as vehicles for transmitting antibiotic resistance to the gut microbiome. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

The U.S. Centers for Disease Control and Prevention estimated that of the 2 million antibiotic-resistant infections per year in the U.S., 20 percent are linked to agriculture. This estimate is based on patients who directly acquire antibiotic-resistant superbugs from eating meat. Little has been done to determine how eating plants contributes to the spread of antibiotic-resistant “superbugs.”

“Our findings highlight the importance of tackling foodborne antibiotic-resistance from a complete food chain perspective that includes plant-foods in addition to meat,” said Marlène Maeusli, PhD candidate at Keck School of Medicine at the University of Southern California, who is the lead author on the study.

Spread of antibiotic-resistant superbugs from plants to humans is different from outbreaks of diarrheal illnesses caused immediately after eating contaminated vegetables. Superbugs can asymptomatically hide in (or “colonize”) the intestines for months or even years, when they then escape the intestine and cause an infection, such as a urinary infection.

The researchers developed a novel, lettuce-mouse model system that does not cause immediate illness to mimic consumption of superbugs with plant-foods. They grew lettuce, exposed the lettuce to antibiotic-resistant E. coli, fed it to the mice and analyzed their fecal samples over time.

“We found differences in the ability of bacteria to silently colonize the gut after ingestion, depending on a variety of host and bacterial factors,” said Maeusli. “We mimicked antibiotic and antacid treatments, as both could affect the ability of superbugs to survive passage from the stomach to the intestines.”

Exposure to one type of antibiotic did not increase the ability of superbugs to hide in the mouse intestines, whereas a second antibiotic resulted in stable gut colonization after ingestion. Ingestion of bacteria with food also changed colonization, as did administering an antacid before ingesting the bacteria.

“We continue to seek the plant characteristics and host factors that result in key microbial community shifts in the gut that put us at risk for colonization and those that prevent it,” said Maeusli. “The environment and human health – in this context via agriculture and microbiomes – are inextricably linked.”

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This study was conducted by Marlène Maeusli, Z. Reyna, J. Yan, P. Lu, B. Lee, N. Guerrero, A. Ulhaq, Y. Talyansky, B. Luna, N. Skandalis, B. Spellberg of the Keck School of Medicine at the University of Southern California, Los Angeles, CA, U.S.A. This work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health Grant Numbers R01 AI117211 and R01 AI130060 to BS, and R01 AI139052 to BL. This poster will be presented at ASM Microbe 2019 in San Francisco, CA on Saturday, June 22nd (11am – 12pm PST and 4pm – 5pm PST).

ASM Microbe is the annual meeting of the American Society for Microbiology, held June 20th through 24th in San Francisco, California.

https://www.eurekalert.org/pub_releases/2019-06/asfm-pmb061719.php

Metformin An Anti-Aging Pill? Think Twice

A popular diabetes drug sometimes taken to slow aging may diminish some of the expected health benefits of aerobic exercise in healthy older adults, according to a new report. The drug, metformin, can blunt certain physical changes from exercise that normally help people to age well.

The results raise questions about the relationship of pills and physical activity in healthy aging and also whether we know enough about how drugs and exercise interact. The results are particularly disconcerting given that healthy, active people may be considering taking the drug to slow aging.

Metformin currently is the most-prescribed medication globally for people with Type 2 diabetes. It allows people with Type 2 diabetes to improve their blood-sugar control and insulin sensitivity, in large part by reducing the amount of sugar released by the liver into the blood. In people with diabetes, the benefits can clearly outweigh the risks.

But in recent years, scientists, physicians and plenty of other people entering middle age have become intrigued by the idea that it might also change how healthy people age. Worms and rodents given metformin typically outlive their unmedicated labmates. These animal studies suggest that the drug not only reduces blood sugar, it also reduces inflammation and produces other cellular effects that alter aging.

Exercise also influences aging, of course. Animal and human studies show, for example, that regular activity raises people’s aerobic fitness and increases their insulin sensitivity, both of which are linked with longer, healthier life spans.

Unsurprisingly, some researchers have speculated that combining metformin and exercise might lead to even greater anti-aging benefits than either approach alone. But little has been known about just how and whether metformin and exercise might work together deep inside our bodies and cells.

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So, for the new study, which was published in February in Aging Cell, researchers at the Oklahoma Medical Research Foundation, Colorado State University and the University of Illinois decided to ask healthy people to sweat and swallow metformin.

They began by recruiting 53 sedentary but otherwise healthy men and women in their early 60s. Most had risk factors for Type 2 diabetes, such as a family history, but were not diabetic.

The researchers measured the volunteers’ current aerobic fitness, blood-sugar levels, insulin sensitivity and body mass. They also took tiny leg-muscle biopsies and randomly assigned the volunteers to start taking either metformin or a placebo.

All of the volunteers then began a supervised exercise program, visiting the lab three times a week to jog on a treadmill or pedal a bike for 45 minutes, a routine that lasted for four months.

Afterward, the researchers repeated all of the measurements from the study’s start and compared the two groups.

It turned out, to no one’s surprise, that most of the volunteers now had better aerobic fitness and blood-sugar control than before, as well as improved insulin sensitivity. Each of these physiological changes would be expected to improve how well the volunteers aged.

But there were notable disparities between the two groups. Over all, the men and women taking metformin gained less fitness, upping their endurance by about half as much as those swallowing the placebo. Many of those taking the drug also showed slighter, if any, improvements in insulin sensitivity. (Hardly anyone’s weight changed much, in either group.)

The scientists next looked microscopically inside their volunteers’ muscles and found telling discrepancies between the two groups. The muscle cells of the exercisers on placebo teemed with active mitochondria, which are the cells’ powerhouses. Mitochondria transform oxygen and sugar into cellular fuel in a process referred to as mitochondrial respiration. Higher respiration generally means better cellular health.

In the muscle cells from the men and women on placebo, mitochondrial respiration rose by about 25 percent, compared to levels at the study’s start. But not so in the muscle cells from the metformin group, which showed little if any upswing in mitochondrial respiration.

In effect, metformin had road-blocked the normal exercise-related gains in muscle-cell mitochondrial respiration, says Benjamin Miller, a principal investigator in the aging and metabolism research program at the Oklahoma Medical Research Foundation, who oversaw the study.

Without these souped-up mitochondria, the exercisers on metformin seemed less able to improve their fitness or insulin sensitivity than the other volunteers.

These results do not mean that people should stop or avoid using metformin, Dr. Miller cautions, even to brake aging. The study followed only a small group of people for a relatively short period of time and examined a mere fraction of the voluminous bodily impacts of exercise and metformin. It also did not include people taking metformin without exercise.

But the findings “do give us reason to think a bit more cautiously” about mixing metformin and exercise in healthy people, Dr. Miller says.

“There was not an additive effect” from combining them, he says. Instead, metformin and exercise “did not seem to play together very well.”

More research is needed, though, to understand how metformin affects mitochondria, exercise and aging, he says. More broadly, the results raise questions about how exercise might respond to other medicines.

“Doctors are very cognizant of drug-drug interactions,” he says. “It’s time we consider drug-and-exercise interactions, too.”

New discovery could improve therapies for Duchenne muscular dystrophy

A new multi-institution study spearheaded by researchers at Florida State University and the University of California, Los Angeles suggests a tiny protein could play a major role in combating heart failure related to Duchenne muscular dystrophy (DMD), the most common lethal genetic disorder among children.

In collaboration with scientists from across the nation, FSU researchers found that increased levels of the protein sarcospan improve cardiac function by reinforcing cardiac cell membranes, which become feeble in patients with DMD.

Their findings were published in the journal JCI Insight.

The condition, which typically afflicts young boys, is caused by a mutation that prevents the body from producing dystrophin, a protein crucial to the health of skeletal, respiratory and cardiac muscles. Advances in treatment for certain types of DMD-related muscle degradation have helped to prolong patients’ lifespans. However, as DMD patients age, their heart function declines dramatically.

Patients typically live to 20 or 30 years of age. There have been important improvements in respiratory care, which used to be what a majority of patients would succumb to. Now, in their 20s and 30s, they’re often succumbing to cardiomyopathy. The heart is functioning with a major component of the cell membrane missing. Over time, it wears out.”

Lead author Michelle Parvatiyar, an assistant professor in the Department of Nutrition, Food and Exercise Sciences in FSU’s College of Human Sciences

The study was part of continued efforts by UCLA biologist Rachelle H. Crosbie, the study’s corresponding author, who previously identified sarcospan as a protein that could improve mechanical support in skeletal cell membranes lacking dystrophin. Her finding buoyed DMD researchers and affirmed sarcospan’s potential as an effective tool in the fight against the condition.

“But nobody had really looked at how increasing the levels of this protein might affect the heart,” Parvatiyar said.

Using a unique mouse model with a dearth of dystrophin, Parvatiyar and her collaborators did just that.

In their study, the team found that while it’s is not a like-for-like replacement for dystrophin, an overexpression of sarcospan in cardiac cells seems to do the job of stabilizing cell membranes. Even under stress, researchers found, sarcospan overexpression was able to improve the membrane defect in dystrophin-deficient cells.

“Sarcospan doesn’t quite do the job of dystrophin, but it acts as a glue to stabilize the membrane and hold protein complexes together when dystrophin is lacking,” said Parvatiyar, explaining a concept developed by Crosbie.

Cardiac measurements confirmed that sarcospan does protect the cell membrane even when the heart is placed under stress. Study co-author and FSU College of Medicine Associate Professor Jose Pinto performed the measurements, along with FSU graduate student Karissa Dieseldorff Jones and University of Miami Miller School of Medicine research assistant Rosemeire Takeuchi Kanashiro.

In addition to serving as a kind of stabilizing glue, researchers said sarcospan could also act as a scaffold that supports other essential proteins at the cell membrane. That function could allow sarcospan to carry mini versions of dystrophin -; which, in its normal state, has a long and unwieldy genetic code -; to the edges of cardiac cells, where they could buttress the fragile membranes.

“The idea is that you could administer the sarcospan and the dystrophin at the same time, and the sarcospan could facilitate mini dystrophin localizing to the cell membrane and help hold those complexes in place,” Parvatiyar said.

Sarcospan’s two possible functions could augment existing DMD treatments, Parvatiyar said, or they could give rise to novel therapies that fortify weakened cardiac cell membranes and improve the quality of life for people with DMD.

In her previous position at UCLA, Parvatiyar had frequent interactions with DMD patients and their families. She said these interactions, and the unshakeable hope she’s witnessed in those suffering from DMD, continue to drive her and her colleagues in the search for new ways to combat this debilitating condition.

“Those were the first times in my life I’d ever had someone come up to me and thank me for my work,” she said. “Sometimes you can feel removed from it in the laboratory day after day. You see incremental progress. But to see people who are really yearning for help is motivating. Their positivity is incredibly inspiring.”

Source:

Florida State University

Journal reference:

Parvatiyar, M.S. et al. (2019) Stabilization of the cardiac sarcolemma by sarcospan rescues DMD-associated cardiomyopathy. JCI Insight. doi.org/10.1172/jci.insight.123855.

https://www.news-medical.net/news/20190616/New-discovery-could-improve-therapies-for-Duchenne-muscular-dystrophy.aspx

Amazon gets U.S. patent to use delivery drones for surveillance service

Amazon.com Inc is exploring using drones not just to deliver packages but also to provide surveillance as a service to its customers, according to a patent granted by the United States Patent and Trademark Office.

The delivery drones can be used to record video of consented user’s property to gather data that can be analyzed to look out, say for example, a broken window, or a fire or if a garage door was left open during the day, the patent described.

According to the patent, the surveillance function of the drone can be limited through geo-fencing, a technology used to draw a virtual boundary around the property under surveillance. Any image or data that the drone captures outside the geo-fence would be obscured or removed.

The application for the patent was filed by the e-commerce giant in 2015 and granted on June 4.

Earlier this month, Amazon said it will start drones delivering packages to customers in 30 minutes or less in the coming months.

https://www.marketscreener.com/news/Amazon-gets-U-S-patent-to-use-delivery-drones-for-surveillance-service–28796224/?countview=0

Combination of drugs may combat deadly drug-resistant fungus

As health officials in New Jersey, Illinois and New York State scramble to contain the spread of a highly infectious and deadly fungus, microbiologists at Beth Israel Deaconess Medical Center (BIDMC) have shown that a combination of anti-fungal and anti-bacterial medications may be an effective weapon against the recently discovered multidrug resistant, Candida auris (C. auris).

BIDMC’s Thea Brennan-Krohn, MD, presented the findings Friday, June 21, 2019, at ASM Microbe 2019, the annual meeting of the American Society for Microbiology.

“Few treatment options are available for patients infected with Candida auris, which causes invasive, life-threatening infections, usually in patients who are already critically ill or have compromised immune systems,” said Brennan-Krohn, MD, a post-doctoral research fellow in the lab of James E. Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC. “It has an alarming propensity to spread from patient to patient and survive on surfaces in rooms, resulting in hospital outbreaks.”

First discovered in Japan in 2009, C. auris has been detected in patients in more than 20 countries and, as of April 2019, has sickened 643 Americans in 11 U.S. states, according to the U.S. Centers for Disease Control and Prevention (CDC). At present, most cases of C. auris are resistant to at least one antifungal drug, with about a third impervious to two or more.

In order to identify new treatment approaches for C. auris, Brennan-Krohn and colleagues used a modified inkjet printer — a method pioneered for rapid and uniform antimicrobial screening in the Kirby lab — to test three antifungal drugs, one from each of the main classes of antifungals, combined with two antibacterial antibiotics, which by themselves have no activity against fungal infections.

Using the inkjet technology to dispense uniform samples of C. auris into each of the 96 wells in a standard lab testing plate, Brennan-Krohn tested 10 combinations against 10 strains of C. auris, a painstaking process that would have taken at least 50 hours if done by hand. It took less than two hours in total using the inkjet dispenser for Brennan-Krohn to find three novel combinations of antifungal and antibacterial drugs that demonstrated activity against this insidious new pathogen.

Using a different method known as a time-kill test, Brennan-Krohn showed that two of the antibacterial-antifungal treatments not only prevented C. auris from growing but also succeeded in killing some of the strains tested.

While the drugs have not yet been tested in combination in humans infected with C. auris, all of the drugs Brennan-Krohn evaluated — the antifungals amphotericin and caspofungin and the antibacterials minocycline and rifampin — are FDA-approved antibiotics, currently in use patients with a variety of infections. If the drugs’ combined power to inhibit or kill C. auris that they demonstrated in the lab is confirmed in studies in humans, it could mean physicians caring for patients with C. auris infections already have access to effective treatment options.

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Story Source:

Materials provided by Beth Israel Deaconess Medical Center. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2019/06/190621154915.htm

Novartis MS drug price ‘out of line with benefit’: ICER

A U.S. group that reviews the value of medicines issued a critical report on Novartis’s new multiple sclerosis drug Mayzent, calling its $88,561 list price “far out of line” compared with its benefits for patients.

The Boston-based Institute for Clinical and Economic Review (ICER), which has been reviewing Mayzent for months, recommended that Novartis lower the drug’s price.

Novartis disputed the findings.

Mayzent was approved in March by the U.S. Food and Drug Administration for adults with relapsing forms of multiple sclerosis, including active secondary progressive disease (SPMS).

The FDA concluded oral Mayzent was not shown to be effective in forms of MS where relapses have stopped but the disease continues to progress, also known as non-active SPMS.

“It is unfortunate that Novartis chose a price that is so far out of line with (Mayzent’s) benefits to patients with active SPMS, particularly with it entering a crowded field of disease modifying therapies,” ICER Chief Medical Officer David Rind said in a statement late on Thursday.

Novartis said feedback and recommendations it gave to ICER were not taken into account, adding the U.S. group did not use the right comparisons to establish cost effectiveness of drug.

“Novartis believes that Mayzent brings value to MS patients,” a company spokesman said, adding Mayzent had demonstrated a significant effect in delaying disability progression in a representative SPMS population.

The conclusions of ICER are used by insurers, pharmacy benefits managers and government agencies in the United States as they negotiate reimbursement for medicines with drugmakers.

Some patient groups funded by the drug industry have been critical of ICER’s reports, saying the standards it uses to judge a drug’s value are discriminatory.

https://www.reuters.com/article/us-novartis-icer/u-s-group-says-novartis-ms-drug-price-out-of-line-with-benefit-idUSKCN1TM0H3

J&J challenges Okla. opioid abatement projections

The state of Oklahoma unveiled a 30-year plan to abate Oklahoma’s opioid epidemic Friday that would carry a hefty price tag of more than $17.5 billion.

The detailed abatement plan was slowly revealed Friday during Day 19 of testimony in a trial in Cleveland County District Court where Oklahoma Attorney General Mike Hunter has accused Johnson & Johnson and its subsidiaries of creating a public nuisance that helped cause the opioid crisis.

The state has accused the opioid manufacturer of false and deceptive marketing that downplayed the risks opioid painkillers while overstating their benefits.

From 2000-2017, there were over 6,100 prescription opioid-related deaths in Oklahoma, state officials say.

The attorney general wants District Judge Thad Balkman to order Johnson & Johnsonto pay the state to fix the opioid abuse problem.

Jessica Hawkins, senior director of prevention services for the Oklahoma Department of Mental Health and Substance Abuse Services, has spent two days testifying about how the proposed $17.5 billion in abatement money would be spent.

Methodically, she described all the proposed expenditures as “reasonable and necessary” to accomplish the abatement goal.

In some cases, she insisted the projections were even “conservative.”

Attorneys for Johnson & Johnson quickly challenged that assertion.

Johnson & Johnson attorney Stephen Brody quizzed Hawkins about why the state would include $1.3 billion for universal drug and alcohol screening of SoonerCare patients when Medicaid is already picking up the cost for those services.

Hawkins snapped back that there had been testimony in court about Johnson & Johnson’s role in creating the opioid crisis and she didn’t think it was the taxpayers’ responsibility to pick up the tab.

Brody also questioned Hawkins about why Johnson & Johnson should be required to pay for the screening of patients who had never even taken one of the company’s opioid drugs.

Hawkins insisted that the request is reasonable.

Hawkins described the state’s abatement proposals as “evidence-based” to produce results and contrasted them with a program called “Smart Moves, Smart Choices” that a Johnson & Johnson employee testified the company had developed in collaboration with school nurses to combat prescription drug abuse among teens.

Boulevard Academy in Edmond was one of the schools where the program was taught, the Johnson & Johnson official said.

Hawkins said she has colleagues at the school and they told her they weren’t aware of the program.

“This program is very unlikely to be effective,” Hawkins said, adding that such programs are typically developed by marketing departments to try to make it look like a company is a “good corporate citizen.”

“The don’t work because they’re not supposed to work,” she said.

During earlier testimony, Hawkins outlined a wide array of services and expenditures that she believes are necessary to abate the opioid crisis.

Examples of expenditures she recommended included:

–$693 million for a syringe replacement program to reduce he spread of disease through dirty needles.

–$735 million to purchase technology and hire staff to make it easier for state agencies to share patient information.

–$435 million for community prevention.

–$239 million for higher education discretionary prevention funds.

–$2.4 billion to provide pain prevention and non-opioid pain management programs like yoga and physical therapy to SoonerCare patients.

John Sparks, Oklahoma counsel for Johnson & Johnson and Janssen Pharmaceuticals Inc., criticized the state’s abatement estimates in a prepared statement Friday.

“After four weeks of trial, the state continues on a far-reaching odyssey to seek damages disguised as abatement,” Sparks said. “The state’s proposal, developed solely for this litigation, seeks damages that go far beyond costs related to opioid addiction and abuse. The fact remains that the state has presented no evidence that Janssen products or actions caused Oklahoma’s opioid crisis, and Janssen did everything a responsible company should do.”

Cross-examination of Hawkins is scheduled to continue 9 a.m. Monday.

https://www.marketscreener.com/JOHNSON-JOHNSON-4832/news/Johnson-Johnson-Abating-Oklahoma-s-opioid-epidemic-is-projected-to-cost-more-than-17-5-billion-28799136/