Surveillance of drug-resistant strains of MRSA
As strains of staph continue to adapt and change over time, it is critical for healthcare workers to track these changes. They need to know which strains are present within a community at any point in time, to which antibiotics the strains are resistant, and the severity of disease caused by the circulating strains. Two researchers affiliated with the Department of Molecular Virology Microbiology at Baylor College of Medicine, Drs. Edward Mason and James Versalovic and their colleagues have been conducting surveillance of both HA-MRSA and CA-MRSA in pediatric patients at Texas Children’s Hospital beginning in 2001. By analyzing strains isolated from these patients, the scientists have found that CA-MRSA accounts for an increasing percentage and number of infections. This information can help doctors select the optimal antibiotic treatment for infected patients.
Genetics changes in MRSA
Scientists would further like to understand the genetic changes in MRSA that allow the bacterium to cause serious illness in otherwise healthy individuals. To begin to answer this question, MVM scientists and others at Baylor College of Medicine initiated a project to obtain the DNA sequence of a strain of CA-MRSA called USA300. They chose the USA300 strain, one of two strains that cause the majority of CA-MRSA cases, because it has emerged as the predominant strain causing skin infections, as well as more serious infections, in both pediatric and adult patients in many states. Before 2000 this strain was rarely found in the community; today it accounts for 70 percent of CA-MRSA patients at Texas Children’s Hospital. Another reason for the interest in the USA300 strain is that it appears to be more virulent than other strains.
Drs. Sarah Highlander and Joseph Petrosino and colleagues at the Baylor Human Genome Sequencing Center sequenced the genome of this MRSA-resistant strain from a pediatric patient along with a community-associated staph strain that is susceptible to methicillin. They then compared the DNA sequences. They also compared the DNA sequence of these strains with the previously published staph genomes of isolates obtained elsewhere.
Based on the results of this analysis, the scientists concluded that the USA300 strain that they sequenced was very similar to other staph strains. This suggests that the increased virulence of the USA300 strain is due to subtle genetic changes within its genome. One intriguing finding of their study is that the bacterium has picked up a plasmid that contains a gene that confers resistance to bacitracin, an antibiotic commonly found in over-the-counter skin ointments.
With the genetic information describing USA300 in hand, the scientists can now zoom in on the regions that differ from other strains to pinpoint genes that may account for the ability of USA300 to cause serious illness in some people.
Mechanism of resistance to methicillin
Beta-lactam antibiotics are the most widely used class of drugs for the treatment of bacterial infections. They include penicillin and its derivatives, such as methicillin and amoxicillin. The beta-lactam ring portion of the antibiotic targets the penicillin-binding proteins (PBP), found in the bacterial cell membrane, which function in the synthesis of the cell wall. Binding of the antibiotic to the PBPs prevents the PBPs from performing their essential role and results in the death of the bacterial cell.
Dr. Timothy Palzkill, professor of Pharmacology and Chemical Biology and Molecular Virology and Microbiology, and his research team have been studying mechanisms of resistance to methicillin and other beta-lactam antibiotics. Gram-positive bacteria acquire resistance to beta-lactam antibiotics through the production of a protein called PBP2a, which is able to avoid the inhibitory effects of the antibiotics. This is the mechanism by which MRSA is able to persist despite treatment with multiple beta-lactam antibiotics.
Dr. Palzkill and coworkers conducted a study in which they found that the protein BLIP-II was able to weakly bind and inhibit PBP2a, making it susceptible to beta-lactam antibiotics. They are continuing this line of research by searching for mutations that increase the affinity of BLIP-II to PBP2a.
- Information about symptoms, prevention, and treatment of MRSA from the CDC as well as specific information for athletes, healthcare providers, and school officials
- Information about MRSA from the National Institutes of Health
- More information about MRSA from the National Institutes of Health
- MRSA information from the Texas Department of State Health Services