CARMiG showcases research at national fair

Originally posted on McGovern Medical School News, by Jonathan Garris, Office of Communications.

Dr. William Miller speaks with U.S. Rep. Michael Burgess at the Congressional Antimicrobial Resistance Fair in Washington, D.C. last month.

Professors and researchers with the Center for Antimicrobial Resistance and Microbial Genomics (CARMiG) had the unique opportunity to promote McGovern Medical School’s ongoing research projects on antibiotic resistance at a national fair in Washington, D.C. last month.

A large consortium of groups ranging from government officials to pharmaceutical specialists, medical professionals, funding agencies, and educators gathered for the Congressional Antimicrobial Resistance Fair Nov. 13 to discuss the need to develop new classes of antibiotics, how to responsibly apply them, and advances in diagnostics. Dr. William Miller, assistant professor of medicine in the Division of Infectious Diseases, represented McGovern Medical School at a table that walked attendees through different patient scenarios.

“We have a lot of ongoing research projects that look at the prevalence of antimicrobial resistance, what is actually happening within the bacteria, and how it affects the patient,” Miller said. Some of the key research highlighted focused on examining the genomes of resistant bacteria to help improve diagnostic and treatment methods.

At their table, attendees were given the identity of a patient who had an antimicrobial resistant infection as they followed through the process and challenges of treatment. For example, one attendee might be a solider with a multi-drug resistant infection called Acinetobacter, prevalent in those with traumatic injuries. Presenters highlighted where challenges and resistances come into play, and how doctors can respond.

“[Attendees] went all through these different cases to see how antimicrobial resistance impacts their care at the clinical level and beyond,” Miller said.

The appearance marked the first time CARMiG had been invited to the event, and Miller said it was exciting to know that the efforts of the center have been attracting attention and to have a forum highlighting their capabilities. It also was a positive step forward in the field of antimicrobial resistance studies.

“We’ve progressed so far in so many ways – everything from trans-Atlantic airplanes to electric cars – but we’re still using susceptibility testing that goes back half a century,” Miller said. “We need to decrease the amount of time to determine if we have a resistant organism and put people on the correct treatment. It also helps us not give out antibiotics to people who don’t need them.”

Miller said it was an honor to participate in the event and their work was a reflection of the leadership of Dr. Cesar Arias, director of CARMiG and Laurel and Robert H. Graham Faculty Fellow, and the department’s dedicated team.

The center will host a three-day Antimicrobial Resistance Research and Stewardship conference Jan. 17 to 19.

Barbara E. Murray, M.D., receives lifetime achievement award from the Infectious Diseases Society of America

From McGovern Medical School News, by Hannah Rhodes, Office of Public Affairs

William G. Powderly, M.D., president of IDSA, presents Barbara E. Murray, M.D., with the Alexander Fleming Lifetime Achievement Award. Photo credit: IDWeek

Barbara E. Murray, M.D., an internationally recognized infectious disease researcher at The University of Texas Health Science Center at Houston (UTHealth), has been awarded the Alexander Fleming Lifetime Achievement Award from the Infectious Diseases Society of America (IDSA), the organization’s highest honor.

Murray is the J. Ralph Meadows Professor in Internal Medicine and director of the Division of Infectious Diseases, where she has been on the faculty since 1980. Murray has directly sponsored or mentored more than 50 trainees, issued several chapters for text and online books and has published more than 300 articles, which have been cited more than 23,000 times.

She has served on numerous local, national and international committees including the Food and Drug Administration’s Anti-Infective Drugs Advisory Committee, the National Institutes of Health’s (NIH) Recombinant DNA Advisory Committee – for which she also served as chair – and NIH’s Bacteriology and Mycology Study Section.

“Dr. Murray’s contributions have been significant and far-reaching, spanning microbial physiology, virulence, antimicrobial resistance and drug development and IDSA is honored to recognize her with this year’s Alexander Fleming Award for Lifetime Achievement,” said William G. Powderly, M.D., president of IDSA. “She has had a profound impact on the field, her colleagues, her mentors and public health.”

Murray is the current chair of IDSA’s Antimicrobial Resistance Committee. She has undertaken investigations exploring the science that forms much of the foundation for the current understanding of enterococcal drug resistance and pathogenesis. Her extensive research in enterococcal resistance, genotyping, genomics and virulence factors has established many of the modern therapeutic paradigms for these important pathogens.

She has helped characterize new and promising compounds for antibiotic development using a substantial collection of susceptible and resistant organisms that she maintains through guidance to pharmaceutical companies. She was a recipient of a NIH MERIT Award and her research has been NIH-funded for more than 25 years.

Murray was president of IDSA from 2013 to 2014 and has served on the IDSA Board of Directors in multiple roles, including as treasurer for six years and as secretary for three years. A current associate editor for IDSA’s publication Clinical Infectious Diseases, she also served as an editor for Antimicrobial Agents and Chemotherapy for 10 years and is on the editorial boards of several other prominent journals in the field.

The award was presented to Murray at IDWeek 2017 in San Diego last week.

-Adapted from a news release by the Infectious Diseases Society of America

Microbiology research could help better understand protein synthesis

From McGovern Medical School News, by Jonathan Garris, Office of Communications

Dr. Jiqiang Ling

A newly published study led by Dr. Jiqiang Ling, assistant professor in the Department of Microbiology & Molecular Genetics, could change the way researchers look at variations in protein synthesis and could help researchers better understand how pathogens can survive immune responses and antimicrobial treatment.
The article, “Heterogeneity of Stop Codon Readthrough in Single Bacterial Cells and Implications for Population Fitness”, is slated to be published in Molecular Cell’s print edition on Sept. 7 and is currently available online. It describes how researchers from UTHealth, Yale University and Rice University developed a reporter system to visualize the differences of errors during protein synthesis among individual bacterial cells. The study, which took about three years to complete, yielded unexpected results – cells that are slow at making proteins also tend to make more errors.

“This blows my mind as the research field has long been thinking that there is a trade-off between speed and accuracy during protein synthesis,” Dr. Ling said.

The study also showed that individual cells with high errors can grow better under poor-nutrient conditions.

“Sometimes making some errors may help your life, which sounds counterintuitive,” Dr. Ling said.

These findings are particularly important as antimicrobial resistance has become an increasingly severe global threat to human health. A significant reason for the failure of antibiotics is due to a small fraction of pathogen cells evading antibiotics and forming persisters, which can reestablish the bacterial population after antibiotic treatment stops. How persisters are formed is not fully understood

“Our study reveals that bacteria use an active mechanism to fluctuate in the levels of protein synthesis errors among individual cells to facilitate adaptation to changing environments,” Dr. Ling said. “This opens the door for future studies to track protein synthesis errors in pathogen cells in their native environment and help understand how pathogens survive host immune responses and antimicrobial treatment.”

Dr. Yongqiang Fan, a postdoctoral fellow in the Department of Microbiology and Molecular Genetics, and Christopher Evans, a post-candidacy PhD student in the Microbiology and Infectious Diseases Program, are co-first authors of this study. Co-authors include Kalyn Weiss, a first-year graduate student in the Microbiology and Infectious Diseases Program, and Dr. Bill Margolin, professor of Microbiology and Molecular Genetics.

The study joins Dr. Ling’s 15 other published articles since starting his lab in 2013, which have appeared in journals such as the New England Journal of Medicine, American Journal of Human Genetics, Nucleic Acids Research and Nature Review in Microbiology.

“This project has seen many obstacles,” Dr. Ling said. “We are very happy that it is eventually accepted by Molecular Cell.”

Mike Hogg Antimicrobial Resistance Research Seminar Series

December 14, 2017, 4:30 pm

Bioscience Research Collaborative 1003

6500 Main St., Houston, TX 77030


“Ongoing Diversification of Carbapenem-resistant Enterobacteriaceae:

The Menace Continues”

 

Anne-Catrin Uhlemann, MD, PhD

Columbia University


With reception following

[button link= “http://www.gulfcoastconsortia.org/events/mike-hogg-antimicrobial-resistance-research-seminar-series-december-14/”]Register[/button]

Microbiologists find new strategy to combat thrush

From McGovern Medical School News, by Rob Cahill, Office of Public Affairs

From the left: Michael Lorenz, Ph.D., Carrie Graham, M.S, and Danielle Garsin, Ph.D.

An antimicrobial protein caused a dramatic reduction in the creamy white lesions associated with oral thrush in a preclinical study, report microbiologists with McGovern Medical School. Findings appeared recently in the Proceedings of the National Academy of Sciences of the United States of America.

Oral thrush is a fungal infection of the mouth and throat that affects millions worldwide. Babies, seniors and people with weakened immune systems are particularly susceptible.

“The long-term vision is to develop a new antifungal drug that takes a different approach to treating oral thrush,” said Danielle Garsin, Ph.D., the study’s co-principal investigator and an associate professor of microbiology and molecular genetics.

Garsin and her collaborator, Michael Lorenz, Ph.D., tested the effectiveness of the antimicrobial protein (EntV) in a mouse model of oral thrush. “The animals who were treated with the protein had far fewer symptoms than the control animals,” said Lorenz, a professor of microbiology and molecular genetics.

Because this particular type of fungus – Candida albicans- can develop resistance to medications over time, there is always going to be a need for new antifungals, Lorenz said.

“While thrush is normally not a major problem for patients with normal immune systems, it can be particularly severe and difficult to treat in immunocompromised patients who have been exposed to multiple antifungals and can develop resistant strains of yeast,” said Luis Ostrosky-Zeichner, M.D., director of the Laboratory of Mycology Research, professor of infectious diseases and vice-chair of internal medicine.

“Furthermore, development of new antifungals is encouraging in the face of emerging multidrug-resistant yeasts like Candida auris,” said Ostrosky, who is medical director of epidemiology for Memorial Hermann-Texas Medical Center.

Traditional antifungals stop Candida albicans from growing, but do not kill it, which leads to the rise of drug resistance. In contrast, the EntV protein appears to block the ability of Candida to cause disease but does not affect its growth. “The thought is that a treatment that just blocks virulence reduces the incentive for the microbe to evolve drug resistance. That’s one of several things that is different about our strategy,” Lorenz said.

Post-graduate doctoral student Carrie Graham, M.S., the study’s lead author, said EntV blocks the biofilm development that allows the fungus to grow in a complex community on the tongue and walls of the mouth and increases resistance to traditional antifungal drugs.

EntV is a protein made by Enterococcus faecalis, a bacterium found in the gastrointestinal tract.

“In an earlier test where we combined Candida albicans and Enterococcus faecalis, we thought they would make each other more virulent. Instead, they actually reduced the other’s virulence,” Garsin said.

Lorenz said the next step in the research will be to learn more about the molecular mechanisms by which EntV inactivates Candida. “We are also testing whether EntV will work against other types of fungal infections,” he said.

The study titled “Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans” was supported in part by by National Institutes of Health awards (R01AI075091, R01AI076406, R01AI110432 and F31AI1222725). McGovern Medical School senior research assistant Melissa Cruz, B.S., was a co-author.

Graham is a student at The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, where Garsin and Lorenz serve on the faculty.  Ostrosky, Lorenz and Garsin are members of the Center for Antimicrobial Resistance and Microbial Genomics (CARMiG) at UTHealth.

Antibiotic Resistance Symposium: Novel Frontiers in Antimicrobial Research

Photos by Dwight C. Andrews/ Office of Communications; Original Post on UTHealth Scoop


Faculty, researchers and students from McGovern Medical School participated in the Antibiotic Resistance Symposium : Novel Frontiers in Antimicrobial Research January 19-20 at the Rice University Bioscience Research Collaborative. The event was sponsored by the Gulf Coast Consortia, a seven member organization made up of  translational scientists, researchers, clinicians and students in the quantitative biomedical sciences.

 

UTHealth celebrates launch of collaborative superbug research center

Published: December 16, 2016 by Hannah Rhodes

Earlier this year, the United Nations designated antibiotic resistance as a global health priority and emphasized that collaboration would be key to slowing the spread of deadly superbugs. With that in mind, Cesar Arias, M.D., Ph.D., was already at work forming the Center for Antimicrobial Resistance and Microbial Genomics (CARMiG) at UTHealth, a multi-institutional effort to combat the global threat of antibiotic resistance.

UTHealth celebrates launch of collaborative superbug research center
Cesar A. Arias, MD, PhD

Arias was also recently named chair of the newly-formed Gulf Coast Consortia – Antimicrobial Resistance Cluster, an inter-institutional cooperative with a focus on building strong collaborative research groups and interdisciplinary training opportunities for Ph.D. and postdoctoral students.

“If the problem continues at this pace, we’re going to have a huge loss of life and economic output. It’s tremendously urgent for us to step up and do something about it,” Arias said during the opening ceremony for the new center on Nov. 29.

A number of local and global leaders praised Arias and UTHealth for the collaborative nature of the center and how it can help address a complex problem. Remarks were made during the opening ceremony by representatives from Rice University, The University of Texas MD Anderson Cancer Center, University of Houston, The University of Texas Medical Branch at Galveston, Baylor College of Medicine, Houston Methodist, Universidad El Bosque in Colombia and the British Consulate General.

“I think that we all can be proud, Cesar, of what you your team have accomplished and will accomplish with this new center,” said Barbara J. Stoll, M.D., dean of McGovern Medical School and H. Wayne Hightower Distinguished Professor in the Medical Sciences.

A common theme of the evening was the complexity of addressing antibiotic resistance. Keynote speaker Arjun Srinivasan M.D., associate director for Healthcare Associated Infection Prevention Programs at the Centers for Disease Control and Prevention (CDC), described the lack of cleanliness in hospital environments, overprescribing of antibiotics, lack of new antibiotics on the market and animal growth hormone use among farmers as the major causes of antibiotic resistance.

“About a third of all the antibiotics that we use, whether that is in emergency departments, outpatient clinics, hospitals or nursing homes, is completely unnecessary. They [illnesses] go away on their own without any detrimental effects to the patients,” said Srinivasan.

According to the CDC, 2 million people are infected with antibiotic-resistant bacteria in the United States each year and 23,000 of those infections lead to death. Srinivasan emphasized that behind these statistics lie individual tragedies.

Following the keynote address, filmmaker Michael Graziano presented the Netflix documentary “Resistance,” which he produced and directed. The film showed the personal stories of people whose lives were suddenly and detrimentally affected by antibiotic resistance. Among the stories was that of a teenager whose father took him to the hospital for what was originally thought to be pneumonia. Within days, his son was in a coma and not responding to antibiotics. The boy survived, but he is still on the road to recovery. The film also explored Denmark’s success in working with farmers to reduce the use of antibiotic growth hormones.

Collaboration is essential to improving the future of global health care, according to Michael Blackburn, Ph.D., executive vice president and chief academic officer at UTHealth.

“Take advantage of the momentum that is established by these new centers, these new collaborative projects, to really work with one another to do what you already do, except to do more of it,” Blackburn said to attendees.

CARMiG will host an Antibiotic Resistance Symposium: Novel Frontiers in Antimicrobial Research Jan. 19 – 20 at the BioScience Research Collaborative (BRC) Building Auditorium, 1st Floor, 6500 Main St. For more information about the event, abstract submission and registration, contact smtomlin@rice.edurosa.gonzalez@uth.tmc.edu or visit CARMiG.net.

Drs. Cesar A. Arias and Yousif Shamoo Interviewed on Houston Matters Radio

Drs. Cesar A. Arias and Yousif Shamoo were recently interviewed on the Houston Matters Radio Show on December 14, 2016.  Visit Houston Matters for the audio:

“How do we prepare for a “post-antibiotic world” – one in which common bacterial infections have become antibiotic-resistant? Some folks right here in Houston are already working on it.

We talk with Dr. Cesar Arias, professor of medicine, microbiology and molecular genetics at UTHealth, and Dr. Yousif Shamoo, vice provost of research and professor of biochemistry and cell biology at Rice University.”

Drs. Shelburne, Shamoo, and Arias published in Houston Chronicle’s Outlook

Drs. Samuel Shelburne III, Yousif Shamoo, and Cesar A. Arias were recently published in the Houston Chronicle’s Outlook.  Read the full article on the Houston Chronicle here, or below.


Shelburne, Shamoo and Arias: We must be smarter about antibiotics use

Thanks to antibiotic medicines, most Houstonians have never lived in a world where run-of-the-mill infections can be deadly. Our grandparents and, in many cases, great-grandparents were the last to live in such a world, but diseases resistant to antibiotics are spreading, and we all will be living in that world again soon.

Houston has the largest medical center in the world and is at the center of the antimicrobial resistance crisis. We and other leaders in the Texas Medical Center are calling for the formation of the Texas Initiative to Combat Antimicrobial Resistance, a statewide effort to galvanize research and make policy recommendations that state and local leaders can act upon to protect Texans from this growing threat.

Antibiotic medications have saved millions of lives since they became widely available in the 1940s, but on every continent, infections are on the rise from bacteria that are resistant to all or nearly all available antibiotics. This is not a problem of the developing world. Antibiotic resistance has a direct impact on health care delivery in the United States, particularly in Texas. Indeed, the U.S. Centers for Disease Control and Prevention conservatively estimates that at least 23,000 people in the U.S. die each year from these infections, and the United Nations estimates the worldwide death toll could reach 300 million by 2050, with a staggering economic toll of $100 trillion.

The first step in addressing the threat is understanding how it arose. For starters, consider that most antibiotic medications are derived from antimicrobial chemicals that are themselves produced by microbes. Single-celled organisms have competed with one another for more than 4 billion years, and just as some have evolved ways to produce chemicals that kill their competitors, others have evolved defenses against those chemicals. The overuse of antibiotic drugs by humans has accelerated how quickly disease-causing organisms have developed such defenses.

In the United States alone, more than 260 million courses of antibiotics are prescribed in outpatient clinics each year, with hundreds of millions more courses given in hospitals. But far more are used in agriculture. Indeed, more than 80 percent of all antibiotics used in the U.S. are given to farm animals, not to fight infection but simply to promote growth.

The problem is compounded by the economics of drug production. As more bacteria become resistant to antibiotics, they become less profitable for drug companies to produce. As a result, major pharmaceutical companies today have stopped investing resources to develop new antibiotics.

Developing new antibiotics should be a national and international priority, but it can take years to create new drugs. In the meantime, we must be smarter about using the antibiotics we have, and local leaders and state officials each have a role to play, as do doctors and citizens.

Building from the experience of Harris County Public Health in tackling infectious diseases such as HIV and tuberculosis, we should devote a similar approach to mitigating antimicrobial resistance in our community. We have only hospital-based, fragmentary knowledge about the problem of antimicrobial resistance in Houston. An active surveillance program should be implemented.

The Cancer Prevention and Research Institute of Texas, which has resulted in dramatic improvements in how cancer is prevented and treated in Texas and beyond, demonstrates how state support for specific health programs can be transformative. Texas can make a similar impact regarding antibiotic resistance.

Finally, the impact of antimicrobial use in farm animals cannot be overlooked. The widespread use of antibiotics in animals destined for human consumption means that we are exposed to antibiotic resistant bacteria in our daily meals. The Department of Agriculture has released a federal plan to combat antimicrobial resistant bacteria, and the state of Texas needs to step up and become a leader in this effort as well.

The entire community should also be aware of the problem and take antibiotics only as prescribed and for the indicated duration of time.

The “post-antibiotic” era is upon us, and Houstonians and Texans should help lead the global fight to halt the spread and minimize the loss of life from antibiotic-resistant disease. We should act now and help the Texas government make a difference in combating this problem.

Shelburne is an associate professor in the department of genomic medicine at MD Anderson Cancer Center. Shamoo is vice provost for research at Rice University. Arias is a professor in the department of internal medicine-infectious diseases at UTHealth.