The Scoop: A Publication of the University of Texas Medical School at Houston

Produced by the Office of Communications // September 15, 2011

Genomic analysis of superbug provides clues to antibiotic resistance

Dr. Cesar Arias

Dr. Cesar Arias

An analysis of the genome of a superbug has yielded crucial, novel information that could aid efforts to counteract the bacterium’s resistance to an antibiotic of last resort. The results of the research led by scientists from the Division of Infectious Diseases are published in the Sept. 8 issue of the New England Journal of Medicine.

Superbugs are bacteria that are resistant to multiple antibiotics and represent one of the most challenging health problems of the 21st century. Infections caused by these bacteria can lead to longer illnesses, extended hospital stays, and, in some instances, death. Antibiotic resistance is on the rise, and alternative treatments are frequently suboptimal.

Researchers focused on a superbug called vancomycin-resistant enterococci (VRE), which is an intestinal bacterium that is resistant to multiple antibiotics, particularly vancomycin, a drug that has been used for treatment of potentially lethal hospital-associated infections.

“It is the second most common bacterium isolated from patients in U.S. hospitals after staphylococci,” said Dr. Cesar Arias, the study’s lead author and principal investigator and associate professor of internal medicine.

“The problem is that VRE has become so resistant that we don’t have reliable antibiotics to treat it anymore,” Arias said. “Daptomycin is one of the few antibiotics left with activity against VRE and is usually used as a drug of last resort. Additionally, this particular superbug is frequently seen in debilitated patients, such as those in critical care units, receiving cancer treatment, and patients receiving transplants, among others; therefore, the emergence of resistance during therapy is a big issue.”

VRE itself can develop resistance to daptomycin during treatment. To find out why, researchers compared the genomes of bacterial samples drawn from the blood of a patient with VRE bloodstream infection receiving daptomycin. The bacterium developed daptomycin resistance, and the patient subsequently died.

By comparing the genetic makeup of the bacterium before and after it developed resistance to daptomycin, the researchers were able to identify changes in genes directly tied to antibiotic resistance. “Our research provides direct substantiation that changes in two bacterial genes are sufficient for the development of daptomycin resistance in VRE during therapy,” Arias said.

“These results lay the foundation for understanding how bacteria may become resistant to daptomycin, which opens immense possibilities for targeting the functions encoded by these mutated genes,” said Dr. Barbara Murray, coauthor and director of the Division of Infectious Diseases.

“This study identified genes never before linked to antibiotic resistance in enterococci,” said Murray, holder of the J. Ralph Meadows Professorship in Internal Medicine. “The genomic approach used in the study is very powerful and was able to pinpoint exactly the specific genes and mutations within them that resulted in the failure of daptomycin (CUBICIN®) therapy and contributed to the fatal outcome of the patient.”

Arias’ laboratory is doing additional research needed to determine the precise mechanisms by which the gene changes allow the bacterium to defeat the antibiotic.

“There are mutations that appear to alter the bacterial cell envelope, which is the target of the antibiotic. The modifications brought about by the gene mutations may change the cell envelope to avoid the killing by these antibiotics. We believe these changes are a general mechanism by which bacteria protect themselves,” Arias said.

“Twenty years ago antibiotic-resistant bacteria more often caused hospital-acquired infections in people with underlying illness or advanced age,” said Dr. Herbert DuPont, holder of the Mary W. Kelsey Distinguished Professorship in the Medical Sciences and director of the Center for Infectious Diseases at the School of Public Health. “Now, resistant bacteria are often seen in the community in otherwise healthy people, making treatment very complicated.”

This research would be a step toward the development of much-needed drugs, Murray added.

The study titled “Genetic Basis for In Vivo Daptomycin Resistance in Enterococci” received support from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Additional Medical School researchers in the study include Drs. Diana Panesso, Lorena Diaz, Truc Tran, and Jung Roh. Coauthors from The University of Texas MD Anderson Cancer Center include Drs. Danielle McGrath, E. Magda Barbu, Renata Pasqualini, and Wadih Arap. Others Houston-area contributors include Dr. Xiang Qin from Baylor College of Medicine and Corwin Miller and Dr. Yousif Shamoo of Rice University.

Other research contributors include Drs. Elizabeth Lobos, Erica Sodergren, and George Weinstock, all from Washington University in St. Louis; Dr. John Quinn from the Chicago Infectious Disease Institute; Maria Mojica from the Center for Medical Research and Training in Cali, Colombia; and Sandra Rincon and Jinnethe Reyes from Universidad El Bosque, Bogota, Colombia.

Arap, DuPont, Murray, and Pasqualini are on the faculty of Graduate School of Biomedical Sciences.

Arias leads the Medical School Laboratory for Antimicrobial Research and the Universidad El Bosque Molecular Genetics and Antimicrobial Resistance Unit in Colombia. Arias’ laboratories have collaborations with several Latin American countries to study specific types of antibiotic-resistant bacteria.

— Robert Cahill, Office of Advancement, Media Relations

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Bone marrow stem cell therapy safe for acute stroke

Dr. Sean Savitz

Dr. Sean Savitz

Using a patient’s own bone marrow stem cells to treat acute stroke is feasible and safe, according to the results of a ground-breaking Phase I trial conducted by Medical School researchers.

The trial was the first ever to harvest an acute stroke patient’s own stem cells from the iliac crest of the leg, separate them, and inject them back into the patient intravenously. The first patient was enrolled in March 2009 at Memorial Hermann-Texas Medical Center. This research, with additional funding from the National Institutes of Health, has been expanded to a larger trial to study safety.

“In order to bring stem cells forward as a potential new treatment for stroke patients, we have to establish safety first, and this study provides the first evidence in addressing that goal,” said Dr. Sean Savitz, principal investigator and associate professor of neurology. “Now we are conducting two other stroke cell therapy studies examining safety and efficacy, one of which can be administered up to 19 days after someone has suffered a stroke.”

The study’s findings were published in a recent issue of the Annals of Neurology. Of the 10 patients enrolled in the study, there were no study-related severe adverse events. Although the study was not intended to address efficacy, the investigators compared the study group with historical control patients, who admitted to the stroke service at Memorial Hermann-TMC before the trial began. In that comparison, the study team found a number of patients who did better compared with controls. However, Savitz said that type of analysis has limitations.

Stroke occurs when blood flow to the brain is interrupted by a blockage or a rupture in an artery, depriving brain tissue of oxygen. It is the third-leading cause of death behind heart disease and cancer and a leading cause of disability. According to the American Stroke Association, nearly 800,000 Americans suffer a stroke each year—one every 40 seconds. The only current treatment for ischemic stroke, the most prevalent kind, is the clot-buster tPA. But only one-third of patients respond well to tPA, so researchers continue to look at other therapies.

Savitz’s other stem cell studies for stroke are using a regenerative therapy developed by Aldagen that uses a patient’s own bone marrow stem cells injected into the carotid artery; and an umbilical cord-derived cell therapy that can be used “off-the-shelf,” which he said he hopes to bring to community hospitals so that a larger number of stroke patients in Houston have access to ground-breaking research testing new potential therapies.

The Stroke Team at UTHealth and Memorial Hermann-TMC was part of the original group of investigators who studied tPA. It is now researching Doppler ultrasound, endovascular treatment, neuroprotection (hypothermia), and new clot-busting medications for ischemic stroke. Clinical trials for intracerebral hemorrhage (bleeding stroke) include a commonly used diabetes drug shown in preclinical trials to speed the removal of blood from the brain, the first and only study of its kind in Houston.

The Department of Neurology is part of the National Institutes of Health’s Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network. The network centers perform early phase clinical projects, share data, and promote new approaches to therapy for acute stroke. The network currently includes eight stroke research centers across the country.

Memorial Hermann-TMC, a primary teaching hospital of UTHealth, was the first Primary Stroke Care Center in Houston, and is the only one to offer stem cell research for stroke. Researchers are affiliated with the Mischer Neuroscience Institute at Memorial Hermann.

For more information on stem cell therapies for stroke, call 713.500.7079 or visit the website.

— Deborah Mann Lake, Office of Advancement, Media Relations

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Faculty Wives and Women Faculty host annual membership tea

Faculty Wives and Women Faculty logo

The Organization of Faculty Wives and Women Faculty welcomes all returning members and those who are new to Houston and the Medical School with its annual membership tea to renew old friendships and make new ones.

Cathy Weisbrodt, the group’s membership chairwoman, and the rest of the Board invite all existing and new members to the annual Fall Tea, 10 a.m.–noon, Saturday, Sept. 17 at the home of Gerlind Wolinsky, 3311 Rice Boulevard.

Faculty Wives and Women Faculty would love to introduce the new women to the group and to Houston, offering help and friendship as they settle into their new home.

To attend, please respond by telephone to Cathy Weisbrodt at 281.565.0641, or just come!

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NIH announces new research scholars program

National Institutes of Health logo

Starting September 2012, the National Institutes of Health (NIH) will offer a new program that gives 40 medical and dental students the opportunity to work with intramural investigators across the NIH on a variety of research projects.

The Medical Research Scholars Program is designed to prepare clinician-scientists for leadership roles in biomedical research and will offer research experiences in basic science laboratories and in clinical and translational research conducted at the NIH Clinical Center.

— AAMC

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Celebrating research

Dr. Andrew Bean, chair of the Graduate Student Education Committee, left, stands with the winners of the 2011 Dean's Research Scholarship Awards, from left, Bryan Hansen, Jennifer Dulin, Anu Rambhadran, Rachel Reith, Caitlin Elmore, and Shiraj Sen, after the awards ceremony and presentations in the Dean's Conference Room Sept. 15.

Dr. Andrew Bean, chair of the Graduate Student Education Committee, left, congratulates the winners of the 2011 Dean's Research Scholarship Awards, from left, Bryan Hansen, Jennifer Dulin, Anu Rambhadran, Rachel Reith, Caitlin Elmore, and Shiraj Sen, after the awards ceremony and presentations in the Dean's Conference Room Sept. 15.

— Dwight C. Andrews, Office of Communications, Medical School

 

 

 

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Events to know

September 16

Deadline to submit abstracts for oncology poster presentations for the Nov. 12 Oncology CME Conference at Memorial Hermann–Texas Medical Center.
Submit following ASCO 2012 guidelines.

September 19

Bioterrorism and Emerging Infectious Disease Preparedness and Response Series: Dr. Kristy Murray, assistant professor, School of Public Health, presents, “Emerging viruses and consequences for public health: West Nile virus.”
Noon, MSB B.610.

Biochemistry Seminar Series: Dr. Hiro Furukawa (Cold Spring Harbor Laboratory) presents, “Structural Dissection of NMDA Receptor Pharmacology.”
Noon–1 p.m., MSB 2.135.

Department of Integrative Biology and Pharmacology Seminar Series: Dr. Sheng Zhang, assistant professor at the Brown Foundation IMM, presents, “Genetic and Genomic Approaches to Study Human Brain Degenerative diseases using the Fruit Fly.”
4 p.m., MSB 2.135.

September 21

TMC Library and the McGovern Center for Humanities and Ethics panel discussion and lunch, “Implications of Health Care Reform for the Future of Medicine.”
Noon–1:30 p.m., MSB 3.001.
This event is free and open to the public. Register here.

Department of Psychiatry & Behavioral Sciences Grand Rounds: Dr. Dawnelle Schatte, assistant professor of psychiatry, presents, “Update in Medical Student Education in Psychiatry.”
Noon–1 p.m., HCPC Auditorium.
Contact Kristi Rowell for details.

Topics in Neurobiology of Disease: Stem Cells and Regenerative Medicine: Dr. Sean Savitz, associate professor of neurology, presents, “Stroke and Cell Toxicity.”
Noon, MSB 7.037.
Sponsored by the Neuroscience Research Center and GSBS.

September 22

Department of Surgery Grand Rounds: Dr. Lillian Kao, associate professor of surgery, presents, “Disclosures of Surgical Errors.”
7 a.m., MSB 3.001.
CME credit is available.

Microbiology and Molecular Genetics Seminar Series: Dr. K.C. Huang (Stanford University) presents, “The sinister truth behind the E. coli cell wall.”
10:45 a.m., MSB 2.135.

September 26

Bioterrorism and Emerging Infectious Disease Preparedness and Response Series: Dr. Wendy Keitel (Baylor College of Medicine) presents, “Influenza Strains, Supply & Schedules: Giving the Right Dose at the Right Time.”
Noon, MSB B.603.

GSBS Town Hall Meeting with Presidents Giuseppe Colasurdo and Ronald DePinho.
Noon–1 p.m., Onstead Auditorium, BSRB, 6767 Bertner, Third Floor.
Bring lunch; drinks will be provided. Contact Brenda Gaughan, 713.599.9857.

Biochemistry Seminar Series: Dr. Matthew Baker (Baylor College of Medicine) presents, “Modeling Macromolecular Machines at Near-Atomic Resolutions.”
Noon, MSB 2.135.

September 27

Research Coordinator Forum: Lance Nickens, president, The Patient Recruiting Agency, presents, “Recruitment Practices for Clinical Trials.”
11:30 a.m.–1 p.m., MSB 2.135.
Lunch will be available for the first 50 attendees.

September 28

Department of Psychiatry & Behavioral Sciences Grand Rounds: Dr. Ian Butler, professor of neurology and pediatrics, presents, “One Observation Leads to Two Observations and a Case Report Leads to a Career in Child Neurology and Mentoring.”
Noon–1 p.m., HCPC Auditorium.
Contact Kristi Rowell for details.

Topics in Neurobiology of Disease: Stem Cells and Regenerative Medicine: Dr. Charles Cox, professor of pediatric surgery, presents, “Cellular Therapy for Traumatic Brain Injury.”
Noon, MSB 7.037.
Sponsored by the Neuroscience Research Center and GSBS.

September 29

Microbiology and Molecular Genetics Seminar Series: Dr. Slavena Vylkova (postdoctoral fellow, laboratory of Dr. Michael Lorenz) presents, “Environmental pH modulation by Candida albicans.”
10:45 a.m., MSB 2.135.

UTMost

The University of Texas-Houston STAT Neurosonology Laboratory has been granted a three-year term of accreditation in the areas of Intracranial Cerebrovascular Testing and Extracranial Cerebrovascular Testing by the Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL).

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