By Maria-Elizabeth Baeva, Jefferies Lab & Morgan Alford, Hancock Lab
In Fast and Furious, one of the greatest films of all time, Paul Walker almost wins the race against secret villain (spoiler alert) Vin Diesel. Paul activates the “nitro boost” in his car and speeds past his competitor with confidence. What Paul does not realize is that Vin’s car is also nitro-equipped. With a boost of nitrous oxide, both cars move quickly and smoothly and Vin glides across the finish line just moments before Paul.
What if bacteria also had the ability to use nitrogen for a “boost”? Alford et al. recently examined the role of a two-component system called NtrBC in Pseudomonas aeruginosa. They found that this general nitrogen regulator may “boost” the bacteria’s ability to adapt to complex conditions during infection, not unlike the famous Fast and Furious “nitro boost.”
P. aeruginosa is an opportunistic pathogen found ubiquitously in the environment. It is responsible for most infections associated with cystic fibrosis, a genetic disorder that results in excess mucus in the respiratory tract. P. aeruginosa is a successful pathogen in part due to its broad repertoire of adaptive mechanisms which contribute to its ability to thrive in a variety of environments. For example, using techniques such as swarming or surfing, P. aeruginosa can exhibit rapid surface motility and migrate from unfavorable conditions to matrix-encapsulated communities known as biofilms. Biofilms account for many life-threatening infections. They are extremely difficult to get rid of, since bacteria like P. aeruginosa can sustain themselves within biofilms for extended periods of time.
The focus of the study by Alford et al. was a system consisting of two proteins called NtrB and NtrC, previously thought to be involved primarily in nitrogen metabolism. Using a murine cutaneous abscess model for chronic infection, Alford et al. show that NtrBC is also required for P. aeruginosa’s establishment in the host and its spread to other organs. P. aeruginosa NtrBC mutants (∆ntrB, ∆ntrC, and ∆ntrBC) demonstrated a decreased ability to invade and cause damage in the abscess model. In vitro experiments also indicated that the double knockout (∆ntrBC) significantly inhibited biofilm formation, bacterial growth and mechanisms of motility, such as surfing or swarming.
Taken together, these data suggest that NtrBC contributes directly to P. aeruginosa’s broad repertoire of adaptive mechanisms. The authors propose that NtrBC in fact, acts as a global regulator, with RNA transcription profiles of the mutants indicating dysregulated expression of hundreds of genes implicated in infections, in addition to those involved in nitrogen and carbon metabolism. These results suggest that the NtrBC system is particularly important for maintaining P. aeruginosa’s physiological balance, and for enabling the bacteria to adapt to complex conditions during infection.
So, what does this mean for P. aeruginosa infections? What was initially thought to be a simple system for nitrogen metabolism also enables these bacteria to be deadly pathogens. Since the NtrBC system helps the bacteria invade and cause disease, drugs that interfere with NtrBC functionality could be promising therapeutic candidates. Think about it this way: NtrBC could be the difference between P. aeruginosa successfully establishing an infection, or not making us sick. We wouldn’t have ten Fast and Furious movies if Paul and Vinny didn’t have the famous “nitro boost” – perhaps we could prevent sequential bacterial infections if P. aeruginosa didn’t either.
Reference:
- Alford MA, Baghela A, Yeung ATY, Pletzer D, and Hancock REW (2020). NtrBC regulates invasiveness and virulence of Pseudomonas aeruginosa during high-density infection. Front. Microb. 11: 773. doi: 10.3389/fmicb.2020.00773