Nitric Oxide – A Newly Discovered Potential Target for Biofilm Control

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Bacterial Biofilm: Image courtesy of the CDC, Photo credit: Rodney M. Donlan and Janice Carr

Like most humans, bacteria prefer urban environments: cooperation makes earning a living easier, and life in the company of friendly others is generally safer than going it alone. Biofilms, where cells from the same or different species crowd together embedded in a protective glue-like substance called an “extracellular polysaccharide matrix (EPS),” are the bacterial cities of choice. These tiny, yet extraordinarily complex microbes have been building biofilms for billions of years, 3.5 billion years to be precise; they know exactly what they’re doing.

Brush your teeth at night and that pesky film housing billions of bacteria will be back in the morning

From the human perspective, biofilms cause a multitude of problems ranging from dental disease, implant colonization, and chronic urinary tract infections, to the fouling of ship hulls and environmental sensors. Such surface-attached bacterial communities are widespread, persistent and highly resistant to antibiotics, according to Elizabeth M. Boon, PhD, which is why she and her colleagues at Stony Brook University in New York are searching for novel biochemical pathways to use as growth-regulating targets.

Bacteria swim, crawl, walk and chat over dinner

Pseudomonas aeruginosa, for example, swims to find or start a biofilm, crawls to get from one place to another quickly once inside, and then stands up and walks upright to look around. However, survival in crowded, multi-cell environments demands more than just exploring:  it requires extensive maneuvering and negotiation which, in turn, necessitates a sophisticated set of languages. This cell-to-cell communication process, known as quorum sensing (QS), involves the synthesis of small regulating molecules called autoinducers which initiate and sustain a great number of functions; among the best studied are biofilm formation and bioluminescence.

S. woodyi illuminates NO modulation of biofilm building at the molecular level

How bacteria go about establishing a biofilm is widely debated; most scientists agree that the ubiquitous signaling molecule, bis-(3’-5’)-cyclic dimeric guanosine monophosphate (cyclic-di-GMP; c-di-GMP), is involved, says Boon.  Working with the luminous marine bacterium Shewanella woodyi, Boon and collaborators recently identified a previously unknown piece of the puzzle; it appears that nitric oxide (NO), a well-known signaling molecule in mammals, is also a molecular regulator in bacteria and has a significant impact on biofilm formation.

In S. woodyi, as in many bacteria, a heme-nitric oxide/oxygen binding gene known as H-NOX is found near a c-di-GMP gene and the two directly interact.  In the presence of NO, c-di-GMP is degraded and in its absence, c-di-GMP activity is up-regulated, As the intracellular concentration of c-di-GMP goes up, bacteria enter biofilms and as it drops, bacteria become hyper-mobile and more likely to express virulence genes which they’ll need to fend off predators in the outside world, she explains. Although such a mechanism has been suggested by others, this is the first study to demonstrate how NO fine-tunes c-di-GMP metabolism and influences biofilm formation at a molecular level.

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