Acinetobacter baumannii is an opportunistic pathogen that has caused a global outrage in the world of clinicians. The recent rise in the incidence of infections with these bacteria has resulted in an increase of infectious diseases that are extremely difficult to cure. Research has not been able to conclude much about the possible mechanisms by which the bacteria cause pneumoniae, bloodstream infections, and other hospital-acquired diseases. With the severity of the pathogen’s antibiotic resistance, Dr. Edward Geisinger, a biology professor at Northeastern, has taken the initiative of studying Acinetobacter baumannii to solve the problems that this bacterium creates. The Geisinger Lab investigates the molecular basis of antibiotic resistance and disease development in infections with hospital-acquired pathogens. Their research primarily focuses on the bacterium’s biology using animal models and novel research techniques.
Dr. Geisinger graduated from Duke University as a biology major on a pre-med track. During his undergraduate years, he studied abroad in France, taking immunology classes and doing research. He discovered his love for research after working in a biochemistry lab through a course in his freshman year.
“I got hands on experience. I really enjoyed it; I wanted to become a physician scientist,” said Geisinger when asked about his first research experience.
Research is not an easy field to work in, as there is always something new happening every day. Geisinger loves having “the ability to solve a big problem about the unknown, and by doing research you can solve them. Different pieces of puzzles come together.”
His passion for bacteria began during his medical school training in microbial pathogenesis and microbiology training.
While pursuing a MD-PhD at New York University School of Medicine, he conducted various research projects on developmental biology, signal transduction, and cancer biology. His passion for bacteria began during his medical school training in microbial pathogenesis and microbiology training.
“I love pathogens and the different types of diseases associated with them. You see that these little microbes can do these crazy disease processes on host organisms which are many times their size,” he said.
Geisinger transferred his passion for pathogens into his lab work. “I was reading a book by Paul Farmer called Infections and Equalities, while taking the microbiology course in medical school, so the pathology and big picture of social and economic implications of infectious diseases got me interested in microbiology as a research focus,” said Geisinger as he raved about his interest in bacteria.
Geisinger began working with intercellular communication in Staphylococcus. These bacterium communicates with molecules to produce toxins and cause disease. He studied the mechanisms of this pathogen and its different strains, in addition to how they send out signals, and how they are detected by the cells. With this experience, he went to Tufts Medical School for his postdoctoral research and was continued his focus to antibiotic resistance after participating in the treatment of various diseases during clinical trials in medical school.
“I came across a couple of patients who were infected with this one microbe called Acinetobacter baumannii. I recognized it was an emerging problem, so I decided to study their antibiotic resistance and what makes these infections so intractable,” he said.
Geisinger focuses his work on two questions: (1) Does antibiotic resistance influence the ability to cause disease, and (2) could bacterial response to stress be the cause of their ability to spread disease and withstand the innate immune system of the host?
Acinetobacter baumannii experiences a stress response, and the influence of antibiotics make it more aggressive.
Acinetobacter baumannii experiences a stress response, and the influence of antibiotics make it more aggressive. The Geisinger Lab observed that the bacterium alters virulence factors. The bacterium grew more capsule, or the outer layer of a bacterial cell, when subjected to certain antibiotics. These results had them questioning if antibiotics influence the ability of the bacterium to produce an important virulence factor, something it uses to resist the immune system. Geisinger conducted an experiment and found that when bacteria are experiencing stress, a resulting regulatory response makes them more virulent. When experiencing this form of stress, injecting it into a mouse model would make the bacteria lethal and virulent, making it capable of causing disease. Geisinger’s research found that in the presence of antibiotics, microbes can demonstrate augmented virulence, and this further stresses the importance of using the correct drugs. The main question the Geisinger Lab investigates is, “What is the control network that is sensing this type of antibiotic stress and changing the virulence of the pathogen and its resistance?”
Geisinger’s research found that in the presence of antibiotics, microbes can demonstrate augmented virulence, and this further stresses the importance of using the correct drugs.
Dwelling at the molecular level, Dr. Geisinger also aims to identify the resistance genes. He has been successful in identifying a “two-protein system” at the center of the response. It involves a receptor and transcription factor component. The idea is to use this system to learn more about the transduction of signals by this system and the genes it targets to allow for augmented virulence.
A novel tool being used in the lab is Next-Generation DNA Sequencing (NGS) combined with transposon mutagenesis. The transposons are used to produce bacterial mutants which are introduced in Acinetobacter baumannii. Transposons are jumping genes that inactivate by creating a knockout mechanism on whatever gene it jumps to. Normally, the mutants would be isolated and grown in a culture and tested for their phenotype. However, Dr. Geisinger’s used NGS to pool together many transposon mutants to test them out in a single test tube. NGS can be used to see where the mutant is inserted. This sequencing process is done before and after the selective influence of an antibiotic. With this, they conclude which gene was important to grow in the presence of a certain antibiotic. The question then becomes, “Can we identify novel resistance genes in the bacterium?” For which Dr. Geisinger said, “By doing a combined transposon and mutagenesis approach, we can do a mutant hunt of the entire genome and find genes important for virulence and antibiotic resistance.”
When asked about limitations in his research, Dr. Geisinger said, “In order to make Acinetobacter baumannii more amenable to genetics, most of my research employs an older strain not currently present in the clinic. It is important to go back and validate work in a more contemporary isolate, and connect our findings to what is happening in patients.”
The Geisinger Lab is only in its beginning phases at Northeastern, but Dr. Geisinger is eager to recruit a new team of scientists for his lab with fresh perspectives on his research. He is looking for passionate people who are interested in immunology and pathology, and is excited to work with people who can apply their knowledge from classes to a practical lab setting.