Moamen Elmassry is focusing on the pathogen Pseudomonas aeruginosa, which can lead to sepsis if it gets into a patient’s blood.
Sepsis is one of the most troubling conditions in the medical community today. It's the leading cause of death in intensive care units, with an estimated 1 million new cases in hospitalized patients each year in the United States alone.
The condition, in which the body's immune system goes into overdrive trying to kill a blood-borne bacterial infection, is easily treated with antibiotics – the trouble is that the detection time has, in the past, taken longer than it takes for sepsis to kill a patient. So why not just treat every patient with antibiotics to prevent sepsis before it happens? Because overuse of antibiotics leads to increased drug resistance, which makes antibiotics less effective in the future.
It's a tricky situation that researchers the world over have been trying to address in a variety of ways, including a novel, faster-detection device developed in the Texas Tech University Department of Chemistry & Biochemistry. But many of these methods focus on detection and treatment.
What if you could know, ahead of time, why certain patients are more likely to get sepsis? That was the basis of new research being conducted by Moamen Elmassry, a graduate teaching assistant and doctoral candidate in microbiology in the Texas Tech Department of Biological Sciences, in collaboration with the Texas Tech University Health Sciences Center (TTUHSC).
Elmassry's research, which has been accepted for publication in the peer-reviewed journal mSystems, is looking not at sepsis itself, but at the harmful bacteria – called pathogens – that cause the body's exaggerated response. One in particular, Pseudomonas aeruginosa, stood out to him.
"Trauma patients are highly susceptible to blood infections because they have all these injuries and open wounds," Elmassry explained. "We want to identify a new approach or new kind of therapeutic treatment for this pathogen. The best way to do this is actually to see how this pathogen changes its behavior in the blood of trauma patients, and try to see if there are any potential weaknesses we can target. If we can find these kind of changes in the pathogen, we can find new ways to fight it."
Pseudomonas aeruginosa, he said, frequently causes infections in burn and trauma patients. If the infection gets into the patient's bloodstream, it can lead to sepsis. An added danger with Pseudomonas aeruginosa, Elmassry said, is that it's resistant to most of the antibiotics available.
"My research is looking at how this pathogen infects trauma patients and causes sepsis," he said, "and why it has an advantage with these immunocompromised patients."
To do that, Elmassry is examining the genetic response – which genes are activated – when the pathogen gets into the bloodstream.
"We may be able to use these genes as the bacteria's Achilles heel, something that we can target in the future," he said. "We are not sure, but if we find a certain gene that gets activated or deactivated, we can use that as a target for the development of new vaccines or therapeutic treatments."
To do that, of course, he has to study the pathogen in blood, both the blood of people who have undergone trauma and the blood of healthy individuals. Following Institutional Review Board protocols and obtaining informed consent from trauma patients or their family at University Medical Center, Elmassry gets a small sample of the patient's blood.
"Our approach is to simulate sepsis in the lab," he said. "We grow the pathogen directly in the blood of trauma patients, and as a control, we also grow it in blood from healthy volunteers. Using new technologies like next-generation sequencing at the Center for Biotechnology & Genomics that we have here, we identified what genes get activated when it's grown in the blood of trauma patients and in the blood of healthy volunteers.
"We can see from this comparison what genes are really important for the pathogen to grow in the blood of trauma patients. By simulating in the lab the sepsis that happens in patients, we hope to predict, for example, if it's going to be more sensitive to certain antibiotics or more resistant to others, or if it takes advantage of certain chemicals or molecules in the patient's blood to grow, causing sepsis."
Elmassry's requirements for the trauma patient blood are quite specific: it has to be from a physical trauma with multiple injuries, the patient should survive the trauma, and the patient should not already have sepsis.
"The body responds to trauma in different ways, so we needed to see the effect when someone had a major trauma," he explained. "It shouldn't be like someone just fell down – it's probably like a major car accident.
"There is something called the Injury Severity Score, where physicians can score the injury the patient has. It goes from 1 to 75, and 75 is really bad. We were looking at injuries rated at least 15 on this scoring system, because over 15 means it's caused by multiple injuries and there are probably some fractures, while below 15 is a minor trauma, which wasn't the focus of our study."
However, he doesn't take valuable blood from someone who's already lost a lot through a major trauma.
"Also, you try to find the patients who didn't actually develop sepsis in the hospital," he added.
One drawback of the nature of his research, at least from a humane perspective, is that it requires someone to have a relatively severe injury.
"We're looking for blood from trauma patients, so we're very limited with that – you have to wait for someone to get hurt," Elmassry said. "When there's not much to do, sometimes I feel like, 'I guess there aren't any accidents,' which is good – just not for this research."
After some samples had to be discarded, Elmassry was left with a total of seven samples from healthy volunteers and eight from trauma patients. These 15 blood samples were then examined using next-generation sequencing – a DNA-sequencing technology that has revolutionized genomic research – to see what genes were activated or deactivated with the addition of the pathogen.
"Using this tool, we can examine what genes are required for the bacteria to grow in the blood and others that are not," he said. "We have to do this because this bacterium has about 6,000 genes. You can, in theory, look at all of them in the lab, but it would take forever."
A secondary benefit of growing sepsis in a lab environment is that Elmassry can look for ways to detect the condition early in its development.
"One critical point in limiting the treatment of these patients is, whenever these patients get sepsis in their blood, it's hard to detect, so we're trying to see if there is any unique marker for this pathogen that we can detect early on," he said. "If you detect it earlier, you can treat it faster and more efficiently. So we're trying to see if there are any molecules associated with this pathogen that get released in the blood. If so, we can take these markers for early diagnosis of sepsis in these patients."
While Elmassry hopes his work will make a difference in the detection and treatment of sepsis, he doesn't anticipate doing it himself, because he knows it will probably be years, if not decades, before enough research and testing have been done to determine the best method.
"I'm not delusional," he laughed. "I know that, hopefully, we're going to get to something, but we're not going to get to the treatment itself soon. These are just building blocks that someone else is going to continue on."
On that note, Elmassry wanted to thank his collaborators on the research.
"This is a collaborative work between Professor Michael San Francisco in the Department of Biological Sciences and Professor Abdul Hamood in the TTUHSC's Department of Immunology and Molecular Microbiology," he said, "and we want to acknowledge the tremendous support we received as researchers from the Department of Surgery and the Clinical Research Institute at the TTUHSC."