Ecology of Anti-Biofilm Agents I: Antibiotics versus Bacteriophages

Abstract

Bacteriophages, the viruses that infect bacteria, have for decades been successfully used to combat antibiotic-resistant, chronic bacterial infections, many of which are likely biofilm associated. Antibiotics as anti-biofilm agents can, by contrast, be inefficacious against even genetically sensitive targets. Such deficiencies in usefulness may result from antibiotics, as naturally occurring compounds, not serving their producers, in nature, as stand-alone disruptors of mature biofilms. Anti-biofilm effectiveness by phages, by contrast, may result from a combination of inherent abilities to concentrate lytic antibacterial activity intracellularly via bacterial infection and extracellularly via localized population growth. Considered here is the anti-biofilm activity of microorganisms, with a case presented for why, ecologically, bacteriophages can be more efficacious than traditional antibiotics as medically or environmentally applied biofilm-disrupting agents. Four criteria, it can be argued, generally must be met, in combination, for microorganisms to eradicate biofilms: (1) Furnishing of sufficiently effective antibacterial factors, (2) intimate interaction with biofilm bacteria over extended periods, (3) associated ability to concentrate antibacterial factors in or around targets, and, ultimately, (4) a means of physically disrupting or displacing target bacteria. In nature, lytic predators of bacteria likely can meet these criteria whereas antibiotic production, in and of itself, largely may not.

Keywords: Lanchester’s laws; antibiotics ecology; biocontrol; biofilm control; biofilm eradication; biofilms; ecology; phage therapy.

Figure 1

Diagrammatic representation of material presented in Table 1. Arrows point in the direction of antibacterial action, from antibacterial producer to antibacterial target. As abbreviated: “ω” refers to “Offense”, “δ” to “Defense”, “B” to “Before”, “D” to “During”, and “A” to “After”. Orange “Pacman”-like symbols refer to antibacterial deployment that is followed by consumption of target organisms for nutrients, turquoise lightning bolts refer to antibacterial-mediated killing of target organisms for the sake of protection of producing organisms, and yellow crosses refer to antibacterial action against target organisms for the sake of obtaining colonizable surfaces (i.e., “Space”) by producer organisms. The solid, blue horizontal lines refer to intact colonizable surfaces while the brown dashed line refers to an equivalent but disrupted surface. The arrow labeled with ωD-3 (see also Table 1) refers to as effected by either disseminating or instead biofilm-associated bacteria. A second δB arrow, equivalent in placement to the second-from-the-left ωB arrow, has been omitted from the figure to reduce clutter. The actions indicated in the right-hand third of the figure are as potentially effected by fungi.

Figure 2

Overview of phage advantages as anti-biofilm agents in comparison to antibiotics. Bacteria are presented primarily as pink circles and extracellular polymeric substance (EPS) is represented as a blue background. Toward the upper left is a single, lysing, phage-infected bacterium, presented as a gray circle. Arrows emanating from that phage-infected bacterium represent free phages that have been produced, released, and which otherwise are diffusing towards neighboring phage-sensitive bacteria. The loss of blue background, as seen towards the upper-left of the figure, represents the action of EPS depolymerase. These depolymerase enzymes are displayed by phage virions and/or are released locally upon lysis from phage-infected bacteria. Callouts describe properties of obligately lytic phages versus antibiotics as anti-biofilm agents. See Table 3 for additional discussion of these properties.