Researchers Discover the Key to Pseudomonas aeruginosa Virulence

In a recent study, researchers from the University of Georgia have discovered what makes one common bacterium trigger the human immune response and how that microbe can be so pathogenic.

Pseudomonas aeruginosa are Gram-negative, rod-shaped bacteria commonly found in the environment. As an opportunistic human pathogen, P. aeruginosa bacteria causes particularly virulent lung and bloodstream infections in immunocompromised individuals, such as patients with cancer, HIV/AIDS, cystic fibrosis, and burn victims. Hospital patients using breathing machines or catheters, or with surgical or burn wounds are at greater risk for serious healthcare-associated P. aeruginosa infections, and the bacteria can be spread easily through contaminated equipment or the hands of healthcare workers. A 2013 report from the Centers for Disease Control and Prevention (CDC) listed infections from P. aeruginosa at a threat level of "serious," noting that of the 51,000 such infections occurring in the United States each year, about 6,700 are multidrug-resistant, and 440 result in death. Each year, P. aeruginosa infections account for 8% of all healthcare-associated infections in the country, and a study earlier this year found that the rate of drug-resistant P. aeruginosa infections is rising in children.

The way the human immune system responds to pathogenic bacteria in the body may have to do with bacterial structure and motility, according to a new study recently published in the journal PLOS Pathogens. The authors investigated what triggers the first line of defense in the immune response to P. aeruginosa, involving the activation of white blood cells called neutrophils. In the presence of the bacteria, the immune system releases neutrophil extracellular traps (NETs), DNA-based scaffolds affixed to antimicrobial proteins, which work to trap and kill P. aeruginosa bacteria.

Prior to the study, the exact mechanism responsible for NET release was unknown, but the research team discovered that the antimicrobial traps are activated by the organelle that the pathogen uses to swim through the human body. P. aeruginosa bacteria are powered by whip-like flagella that propel the microbes to help them move through the human body and by observing the interplay between the bacteria, and the NETs the research team discovered that the motion of the flagella trigger neutrophils into pathogen-fighting mode, an observation unrecognized until now. "It's a step along the way to direct research attention toward bacterial motility," said author and study leader Balázs Rada in a recent press release from the University of Georgia. "It's an important feature of the bacterium that has been neglected in the past."

The researchers’ first clue to this finding was the observation that conditions in the early bacterial growth stage were activating NET release. Strong swimming powered by flagella is characteristic to the early growth phase of bacteria such as P. aeruginosa. When the researchers tested the immune response reaction to immobilized bacteria with paralyzed flagella, they found that neutrophils did not activate to release NETs. While this immune response is crucial to fighting, the pathogen the authors noted that NETs can also cause tissue damage in those with P. aeruginosa infections and airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease.

"It is important to illuminate the cellular-molecular details of P. aeruginosa-induced NET formation to better understand its clinical relevance in various disorders," noted the authors in the paper. "Our data show that early growth-phase bacteria are the strongest NET-inducers. Our data identify flagellum as the main component of bacteria triggering NETs, thereby filling in a major gap in our understanding of the molecular details of bacterium-triggered NET formation."

As the CDC continues to study antibiotic-resistant P. aeruginosa strains and their impact on hospital patients in the United States, these new findings could help inform how to prevent and fight these infections in those most vulnerable, including individuals with CF. "Loss of the flagellum is one of the characteristic changes accompanying the adaptation of P. aeruginosa in CF airways," the authors concluded. "Our studies provide a potential, novel explanation as to why it is advantageous for P. aeruginosa to lose its flagellar motility early on in colonization of the airways in CF."