Pseudomonas aeruginosa, which is commonly found in hospital settings and can quickly spread between patients, was responsible for 32,600 clinical cases and 2,700 deaths last year, according to a recent Centers of Disease Control report — ranking the pathogen as fifth among bacterial infections that pose a “serious threat” to humans.
While the origin of Pseudomonas aeruginosa infections still remains poorly understood, a Northwestern Medicine study has found that the gallbladder may play a crucial role in the transmission of the pathogen between hospital patients, according to recent findings published in Nature Communications.
“Our results using a mouse model indicate that a small number of Pseudomonas get to the gallbladder, but then they multiply to incredibly high numbers there; it’s almost like a privileged site for Pseudomonas replication because those high numbers are what’s necessary for the bacteria to spread to the intestines, through the feces and then into other hosts,” said Alan Hauser, MD, PhD, vice chair of the Department of Microbiology-Immunology and senior author of the study.
In a hospital setting, Pseudomonas aeruginosa is known to colonize some patient’s gastrointestinal tracts. The pathogen is often antibiotic resistant, posing a hard line of defense to current antimicrobial therapies as it discreetly spreads from patient to patient.
In order to dissect the inner workings of this transmission process, the investigators utilized a mouse model of the bloodstream infection, using a bioluminescent version of Pseudomonas aeruginosa. They then used a technique called sequence tag-based analysis of microbial populations, or STAMP, which utilizes barcoded strains of bacteria in combination with sequencing to track the spread of bacteria, assess infection bottlenecks and assess the relatedness of pathogen populations within different organs.
Through in vivo imaging, the investigators discovered unexpectedly that during bacteremia, Pseudomonas is transmitted from the bloodstream to the gallbladder and subsequently to the intestines and feces. Surgical removal of the gallbladder caused a dramatic decrease in the number of bacteria present in the mouse feces, suggesting that the bacteria used the gallbladder as a site to multiply.
“There are a few pathogens that thrive in the gallbladder, such as Salmonella, but Pseudomonas was not previously reported as one of them,” said Kelly Bachta, MD, PhD, instructor of Medicine in the Division of Infectious Diseases, and first author of the study.
“It’s my hope that we’ll be able to use our findings to begin to think differently about hospitalized patients. Bacteria in a patient’s lungs or in their bloodstream may promote transmission to additional patients in ways we don’t yet fully understand,” Bachta added.
The authors’ long-term goal is to better understand the molecular mechanisms of Pseudomonas aeruginosa that allow colonization in hospital patients and use those findings to develop preventive therapeutic interventions.
“Treatment of these infections is so difficult, but if we can prevent people from getting these infections, then treating them will no longer be necessary,” said Hauser, who is also a professor of Medicine in the Division of Infectious Diseases.
This work was supported by grants from the National Institutes of Health National Institute of Allergy and Infectious Disease (R01 AI118257, R01 AI053674, U19 AI135964, K24 104831, and R21 AI129167) and an American Cancer Society Postdoctoral Fellowship (130602-PF-17-107-01- MPC).