A new roundup of biofilms

Published September 01 2016

Biofilms are sticky. Often slimy and good at adhering to surfaces, these complex microbial communities thrive in moist environments. They can be disruptive. For example, they clog pipes, contribute to dental plaque and wreak havoc with implanted medical devices. Many pathogenic microorganisms that form biofilms pose serious medical problems, as the resulting infections are often difficult to treat.

Biofilms, which can be formed by both bacteria and fungi, create an extracellular matrix made up of proteins, DNA, lipids and sugars. The matrix facilitates molecular communication between the microorganisms within the biofilm to enable adherence to surfaces. The matrix also is involved in the development of antibiotic resistance. The Journal of Biological Chemistry recently published a five-part thematic minireview series that focuses on biofilms and their role in human health and disease. The series was edited by JBC associate editor Norma Allewell at the University of Maryland.

Exopolysaccharides provide functional and structural integrity to biofilms. The first minireview in the series, by Donald C. Sheppard at McGill University and P. Lynne Howell at the University of Toronto, describes their role in pathogenic fungi. Although the enzymes that form fungal biofilms of Candida albicans and Aspergillus fumigatus lack sequence homology with bacterial exopolysaccharide biosynthetic enzymes, they are functionally similar in many ways. The similarity extends to therapeutic targets; for example, a new class of anti-fungal drugs called echinocandins inhibits a beta-1-3 glucan synthase in C. albicans and shows potential anti-biofilm activity.

The second minireview, by John Gunn, Lauren Bakaletz, and Daniel Wozniak at Ohio State University, discusses the extracellular matrix of three bacteria, Pseudomonas aeruginosa, Haemophilus influenza and Salmonella enterica. The authors describe the variety of approaches researchers have taken to target the extracellular matrix, including matrix-degrading enzymes, small-molecule inhibitors and immunotherapeutics. They also suggest that a clearer understanding of the role of the matrix in biofilm production could come via the development of animal models that better mimic human infection.

Martina Valentini and Alain Filloux at Imperial College London investigate the role of cyclic-di-GMP signaling in biofilms with the model organism Pseudomonas aeruginosa in the third minireview. Cyclic-di-GMP is a second messenger that is involved in the life cycle of biofilm formation, which begins with surface attachment, then colony maturation and finally dispersion. Studies of two enzymes involved in cyclic-di-GMP metabolism, mutant diguanylate cylcases and phosphodiesterases, have demonstrated their role in biofilm development. For example, five diguanylate cylcases have been shown to be involved in the transition from the motile to the surface-attached stage.

In the fourth minireview, Jeffery S. Kavanaugh and Alexander R. Horswill at the University of Iowa discuss peptide-quorum sensing in the gram-positive bacterium Staphylococcus. The quorum sensing system is termed the accessory gene regulator, or agr, system. Kavanaugh and Horswill outline the influence of various environmental factors, such as pH, reactive oxygen species and nutrients that can influence the agr system. They also suggest that future work to understand key signaling molecules of the agr system could aid in the development of better therapies to treat staphylococcal infections.

Biofilms are involved in antibiotic resistance, but their involvement is not well understood. In the fifth minireview, Heleen Van Acker and Tom Coenye at Ghent University in Belgium describe two mechanisms of antibiotic resistance. First, they focus on efflux pumps that remove intracellular antibiotics to keep the concentration of the drug below a critical threshold. The authors note that little is known about the regulation and expression of efflux pumps in biofilm growth. The second mechanism they discuss involves persister cells that can tolerate high levels of antibiotic compounds. The authors also explore one confounding area of research, the question of whether persister cells are dormant cells with inactive antibiotic targets or have different metabolic states.

Hailey Gahlon Hailey Gahlon is a Marie Curie postdoctoral research fellow at Imperial College London.