A Research team led by scientists from The University of Texas Health Science Center at Houston (UTHealth) published a paper in the Sept. 8 issue of the New England Journal of Medicine, showing that Antibiotic resistance of a superbug called vancomycin-resistant enterococci (VRE) is being caused by a specific change in its genome.
Bacterial Superbugs that have become resistant to different types of antibiotics are presenting an increasing challenge to the world of healthcare; in fact one could go so far as to say that they will be one of the leading health problems of this century. Antibiotic resistance is becoming a more commonly seen problem that cannot be easily treated with other medicines. The associated problems of the superbug infection often lead to longer illnesses, extended hospital stays and in some cases death.
VRE is an intestinal bacterium that has become resistant to many antibiotics, particularly vancomycin, the drug of choice in dealing with hospital associated infections.
By analyzing the genome of this superbug Cesar Arias M.D., Ph.D., the study’s lead author and principal investigator, (an associate professor of medicine at the UT Health Medical School) found interesting and alternative ways that could be used to combat the bacterium’s resistance to the antibiotic treatment of last resort.
“It is the second most common bacterium isolated from patients in U.S. hospitals after staphylococci. . . .. 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 has been observed to become resistant to daptomycin during the treatment cycle. To investigate the cause, Arias’s research team compared the genomes of bacterial samples taken from the blood of a patient with VRE bloodstream infection receiving daptomycin. The bacteria developed resistance ultimately leading to the patient’s death.
By comparing the genetic makeup of the bacterium before and after it developed resistance to daptomycin, the researchers were able to pin point changes in the bacterium’s genes directly linked to its antibiotic resistance.
Arias said:
“Our research provides direct substantiation that changes in two bacterial genes are sufficient for the development of daptomycin resistance in VRE during therapy.”
Barbara Murray, M.D., coauthor and director of the Division of Infectious Diseases at the UT Health Medical School, 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. This would be a step toward the development of much needed new drugs. That is, once we understand the exact mechanism for resistance, one can start to develop strategies that block or attack the resistance mechanism.”
Murray, holder of the J. Ralph Meadows Professorship in Internal Medicine, continues by clarifying that the study identified genes never before linked to antibiotic resistance in enterococci. She goes on to state that the genomic approach used is very powerful and able to pinpoint the specific genes and mutations within them that resulted in the failure of daptomycin (CUBICIN®) therapy and show how the changes contributed to the fatal outcome of the patient.
Arias’ laboratory is now undertaking additional research to determine the exact mechanisms by which the gene changes allow the bacterium to defeat the antibiotic.
Arias said:
“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.”
Herbert DuPont, M.D. (holder of the Mary W. Kelsey Distinguished Professorship in the Medical Sciences and director of the Center for Infectious Diseases at The University of Texas School of Public Health) goes on to state that:
“Twenty years ago antibiotic-resistant bacteria more often caused hospital-acquired infections in people with underlying illness or advanced age. Now, resistant bacteria are often seen in the community in otherwise healthy people, making treatment very complicated.”
Written by: Rupert Shepherd BSc.