Graduate student Haomin Wang of the Xu Research Group has received the 2018-2019 Roy R. HonorFellowship. This fellowship is awarded to a graduate student for original research in metallurgy and inorganic chemistry.
Uncovering Bacterial Cell Wall Secrets to Combat Antibiotic Resistance
Representation of Staphlococcus aureus
Cell walls—the jacket-like structures that surround all known bacteria—may turn out to be bacteria’s undoing, holding the key to developing new drugs that target it for destruction.
That perspective is shared by many in the medical and scientific communities, including Marcos Pires, a biochemist at Lehigh University. Pires is spearheading a novel approach to understanding bacterial cell wall changes in response to antibiotics that could be critical to new drug design—an urgent need in light of the growing threat of antibiotic resistance. His approach is so promising it has recently been recognized by the National Institutes of Health with a Maximizing Investigators’ Research Award (MIRA).
Antibiotic resistance occurs when bacterial cells adapt to evade a drug designed to kill it. Making changes to the cell wall is one way bacteria accomplish this. Little is known, however, about just how these structures respond when under attack.
With the five-year $1.94 million MIRA grant, Pires’s group will delve deeply into this process through a unique approach that essentially tricks bacteria into revealing where its cell wall is most vulnerable. Such knowledge could help scientists design next-generation antibiotics that circumvent drug resistance mechanisms.
The centerpiece of the research is a process that Pires and his team conduct facilitating live bacteria’s absorption of synthetic cell wall fragments constructed in the lab. These fragments are modified with reporter units, which then allow researchers to observe, in live bacteria, components of the cell wall machinery under various conditions.
“Bacterial cell walls are unique in their structure and function and are essential to bacterial cells—making them unique targets for the development of antibiotics,” said Pires, assistant professor in the Department of Chemistry. “By ‘tricking’ bacteria into using some of our cell wall building blocks, we get an unprecedented perspective on how they change when challenged with antibiotics.”
MIRA is a program of the National Institute of General Medical Science (NIGMS), a division of NIH that provides support for basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention. According NIGMS, the goal of MIRA is to increase the efficiency of NIGMS funding by providing investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs.
Identifying Bacterial Cell Wall Changes that Cause Antibiotic Resistance
The stakes for drug design breakthroughs to treat drug-resistant bacteria are high. Every year in the United States, more than two million people are afflicted with resistant bacterial infections. An estimated 23,000 American lives—and 700,000 lives worldwide—are lost yearly as a result of bacterial infections resistant to current antibiotic treatments. These numbers are only expected to grow.
Bacterial cell walls are the target of some of the most powerful antibiotics discovered to date. Cell wall-targeting antibiotics include some commonly prescribed treatments such as penicillin and amoxicillin. Drugs that target bacteria’s cell walls are also among the safest as human cells do not have cell walls and are thus unaffected by the treatment.
According to Pires, individual components of the bacterial cell wall machinery are key to bacteria’s adaptation response and, therefore, to drug-resistance. One of his team’s goals is to identify the cell wall components that bacteria need to successfully adapt and evade the drugs designed to destroy it.
“If we can identify these ‘weak spots,’ said Pires, “we should be able to find ways to inactivate or circumvent them.”
Another focus area is learning more about the crucial “bottleneck step” in the construction of new bacterial cells. For infections to take hold, bacterial cells need to grow and divide. To do this, the components of new cell walls must be produced inside the cell and then transported outside it. This transport step is known as the “bottleneck” of cell wall production or biosynthesis.
Lipid II, the membrane-anchored cell wall precursor that is essential for this step, is the focus of at least four different classes of antibiotics. The treatment works by interrupting the transport process, thus impeding a bacterial cell’s ability to grow and divide. It is also this transport process that bacteria change in response, rendering antibiotics ineffective.
“We are the first group to be able to ‘pierce in’ and study this ‘bottleneck step’ in live bacteria,” said Pires. “We plan to use our technique to understand it more and to discover how bacteria alter this step to become resistant to antibiotics.”
The Chemistry Department welcomes Dr. Elizabeth Young as Assistant Professor of Chemistry. A native of Macungie, Pennsylvania, Dr. Young received her B.S. in Chemistry (with a minor in German) from Haverford College. After spending a year abroad in Germany, she returned to the U.S. to begin her graduate work at the Massachusetts Institute of Technology in the laboratory of Daniel G. Nocera where she conducted research regarding proton-coupled electron transfer in model systems utilizing electrochemistry and both steady-state and time-resolved spectroscopies. After completing her Ph.D., she received an NSF American Competitiveness in Chemistry Fellowship to sponsor her post-doctoral work with Vladimir Bulovic in the Electrical Engineering and Computer Science Department at MIT. During her post-doc, she learned solid state device fabrication and gained insight about how engineers design organic solar cells.In 2011, Dr. Young joined the Amherst College Chemistry Department as an Assistant Professor. Her research involves investigations of photo-induced proton-coupled electron transfer reactions in model systems and studies of charge transfer dynamics in molecules and materials of interest for next generation photovoltaics. Her work has been funded by the National Science Foundation as well as the American Chemical Society Petroleum Research Fund. At Lehigh, she will establish an experimental physical chemistry laboratory that will include a laser facility for ultrafast transient absorption spectroscopy.
Lehigh University has accepted Electronic Fluorocarbons (EFC) for participation in the Industrial Liaison program at the Lehigh Chemistry Department. In addition, the University has appointed EFC’s Chief Scientist, Dr. Robert Syvret, as a University Research Fellow.
The Industrial Liaison program gives industry participants access to the University’s laboratories and other support services and encourages scientific interactions between the University’s staff and students and the industrial participant.
Congratulations to Dr. Tesia Chciuk of the Flowers Group! She has became the first Lehigh student to receive the Anna Louise Hoffman Award for Outstanding Achievement in Graduate Research from Iota Sigma Pi, the National Honor Society for Women in Chemistry. The award is given annually to one graduate student in the United States.
Six College of Arts and Sciences faculty were recognized for excellence in service and advising when the college hosted its annual faculty awards dinner March 30, 2017 in the University Center’s Asa Packer dining room.
“I continue to be inspired by the service activities produced by our faculty,” said Donald Hall, dean of the college. “Lehigh’s reputation for academic excellence is not possible without the passion and commitment of our faculty. As I reviewed the nominees for recognition in our three different college sectors— arts/humanities, natural sciences/mathematics, and social sciences—I was extremely impressed with the contributions these faculty have made toward the college’s academic mission.”
Dr. James Roberts and two others were recognized for their service to college.
Dr. Roberts, associate professor and vice chair of chemistry, serves as sole Head Usher, assisting the University Marshal at university events such as commencement, doctoral hooding ceremonies, Founders’ Day, Honors Convocation, and Presidential installations. He served head liaison with the university’s technology services during an upgrade of the networking system in Mudd building, overseeing the installation of more than 900 cables in the building and ensuring connections for every room in the building, and serves as chair of the department’s safety committee. At the college level, he serves as an advising mentor and is a member of Alpha Chi Sigma, a national professional organization supporting the chemistry profession. Roberts is also a member of the Lehigh Philharmonic Orchestra, playing in the French horn and trumpet sections. He also performs with various community musical organizations, and serves as scoutmaster for a local troop.
The March for Sciencewas held all throughout the world on Earth Day (Saturday, April 22)! The march demonstrated our passion for science and show our concerns for recent policy changes. The mission was to “unite as a diverse, nonpartisan group to call for science that upholds the common good and for political leaders and policy makers to enact evidence based policies in the public interest.”