Illustration of person pouring prescription medicine into a vat

Angela Brown Leverages Understanding of Bacteria to Combat Antibiotic Resistance

Brown’s research seeks to hijack bacteria’s machinery to develop targeted drug delivery and combat antibiotic resistance.

Story by

Lori Friedman

Photography by

Illustration by Raymond Biesinger

Bacterial infections can take hold in the body when a pathogenic, or disease-causing, microorganism enters and delivers toxins to healthy human cells. One way bacteria accomplish this is by releasing vesicles, which act as tiny envelopes transporting toxins and other virulence factors―molecules that help infection take hold―to host cells. The virulence factors allow the bacteria to effectively infect healthy human cells and make people sick.

The rapid emergence of antibiotic-resistant bacteria―bacteria that do not respond to currently available antibiotic treatment―is a worldwide problem that is only expected to worsen. The Centers for Disease Control and Prevention (CDC) estimates that almost three million people in the U.S. develop antibiotic-resistant bacterial infections each year, with more than 35,000 dying as a result. Developing new antibiotic drugs is a long and expensive process and not widely seen as an effective long-term solution. Anti-virulence strategies that seek to disarm bacteria’s virulence factors are one possible approach.

“The idea of an anti-virulence strategy is to eliminate those virulence factors or inhibit the function of those so the bacteria don’t have those advantages,” says Angela Brown, an associate professor of chemical and biomolecular engineering whose research has focused on anti-virulence strategies. “Then the immune system could have time to clear the infection before it takes hold.”

Illustration

Recently, Brown’s research has taken a promising turn. She is now leveraging her extensive knowledge of bacterial vesicles to develop a better drug-delivery system that could help combat antibiotic resistance.

Brown and her team are harnessing the power of outer membrane vesicles―which are continuously shed by Gram-negative bacteria, the most difficult to treat―to deliver drugs directly to cells. Such a system could decrease the rate of resistance by, among other outcomes, improving delivery to bacteria that are particularly difficult to treat with antibiotics, including those that have developed certain resistance traits.

“Bacterial vesicles as a delivery system have a number of advantages,” says Brown. “They are really stable and they have a natural ability to deliver large molecules to other cells.”

Although other researchers have demonstrated the feasibility of using outer membrane vesicles to deliver medicines, the method has its limitations. Brown’s team is working on a way to overcome those limitations by combining the best properties of outer membrane vesicles with another promising drug delivery strategy: liposomes. Liposomes are synthetically created, nanometer-scale, spherical vesicles that are attractive as drug delivery vehicles because of their solubility and low toxicity. Liposomes’ stability, however, is limited.

“We want to combine liposomes and outer membrane vesicles to create ‘semi-synthetic outer membrane vesicles,’” says Brown. “This will result in a delivery system that maintains the advantages of each system while overcoming the limitations of each.”

Currently, Brown and her team are focused on optimizing the process of loading the drugs into the semi-synthetic vesicles.

“We want to investigate different molecular weights and different hydrophobicities―molecules’ tendency to dissolve or not dissolve in water―and determine what is the best technique to get those particular drugs loaded,” says Brown. “The idea is to make the vesicles more easily modifiable in the future by developing a method that could be applied to a broad range of bacterial infections and antibiotic treatments.”

Illustration of bacteria

Brown is already laying the groundwork to apply her group’s knowledge to address the challenge of treating an emerging multidrug resistant pathogen, Stenotrophomonas maltophilia, that can cause a variety of severe infections in immunocompromised patients.

“The membrane of Stenotrophomonas maltophilia is especially difficult for antibiotics to penetrate so only certain antibiotics can cross,” says Brown. “But if we have these vesicles that naturally fuse with the membrane, like outer membrane vesicles do, we could overcome that resistance pathway.”

Brown’s novel biomaterials-based strategy could become a useful tool for slowing down the rate of antibiotic resistance. If successful, it could even prove to be a new way to repurpose antibiotics that are already in use.

Angela Brown’s research focuses on understanding the mechanisms of bacterial virulence factors during disease pathogenesis to identify targets for the prevention of bacterial diseases and develop biologically inspired therapeutic agents. She received her Ph.D. from Drexel University. 

Story by

Lori Friedman

Photography by

Illustration by Raymond Biesinger

Related Stories

The Center for Gender Equity.

Center for Gender Equity Celebrates 30th Anniversary

The center will mark the anniversary with a ‘ Walk Down Memory Lane’ on Sept. 22 and Sept. 23 from 10 a.m. to noon.

The Rally 2021 with alumni carrying class flags

The Rally Marks Milestone Lehigh Moment

Karen Stuckey ’75 represents Lehigh’s first coed class as it adopts the Class of 2025. It is also the first time that a woman alum presents an incoming class with its official flag.

Rally image

My Soaring Together Story: John O'Hara ’73

Advice from an “Old Timer”