As individual oral bacteria multiply and grow into a dense and sticky biofilm, such as the community that forms dental plaque, their growth patterns and dynamics mirror those seen in the growth of cities, according to researchers using super-resolution imaging technology with a computational algorithm at the University of Pennsylvania School of Dental Medicine.
“We take this ‘satellite-level’ view, following hundreds of bacteria distributed on a surface from their initial colonization to biofilm formation,” said Hyun (Michel) Koo, DDS, MS, PhD, of the Department of Orthodontics and senior author of the work.
“And what we see is that, remarkably, the spatial and structural features of their growth are analogous to what we see in urbanization,” said Koo.
This new perspective on how biofilms grow could help inform efforts to either promote the growth of beneficial microbes or break up and kill undesirable biofilms with therapeutics, the researchers said.
“Usually when people study biofilms, they analyze a single cell in a narrow field of view as it multiples, becomes a cluster, and starts to build up,” said Koo. “But we wondered if we followed multiple individual cells simultaneously whether we could identify some patterns at large length-scales.”
Geelsu Hwang, PhD, an assistant professor in the Department of Preventive and Restorative Sciences, developed time-lapse imaging tools that use confocal laser scanning microscopy capable of analyzing surface topography and tracking bacteria populating a surface down to the individual cell in three dimensions over time.
Amauri J. Paula, PhD, an assistant professor in the Department of Physics at the Universidade Federal do Cearáin Brazil, built an algorithm that could analyze the behavior of this growth over time.
For their study, the researchers used Streptococcus mutans, which causes cavities when it forms dental plaque and releases acids that decay enamel. The researchers distributed the bacteria on an enamel-like material and followed hundreds of individual microbes during several hours as they divided and grew.
The growth patterns were reminiscent of the formation of urban areas, the researchers found. Some individual “settlers” grew, expanding into small bacteria “villages.” As the boundaries of the villages grew and in some cases met, they joined to form larger villages and eventually “cities.” Some of these cities then merged to form “megacities.”
However, only a subset of the bacteria grew.
“We thought that the majority of the individual bacteria would end up growing,” said Koo. “But the actual number was less than 40%, with the rest either dying off or being engulfed by the growth of other microcolonies.”
The researchers also didn’t expect a lack of inhibition when this engulfment took place. They thought that, as different microcolonies met, they might compete with each other, causing the two edges to perhaps repel.
“Instead, the merge and begin to grow as a single unit,” said Koo.
On both the individual bacteria and biofilm-wide scale, the researchers confirmed that the gluelike secretion known as extracellular polymeric substances (EPS) enabled bacteria to pack together closely and firmly in the biofilm. When they introduced an enzyme that digested EPS, the communities dissolved and returned to a collection of individual bacteria.
“Without EPS, they lose the ability to densely pack and form these cities,” said Koo.
Finally, the researchers experimented to see how the addition of a microbial friend or foe would influence the original bacteria’s growth.
The foe, Streptococcus oralis, can inhibit the growth of S mutans. This addition dramatically impaired the ability of S mutansto form larger cities, like disruptive neighbors that can affect the collective growth of the community.
The friend, the fungus Candida albicans, which Koo and others have found to interact with S mutansin biofilms and to contribute to tooth decay, did not affect the biofilm’s growth rate but did help bridge adjacent microcolonies, enabling the development of larger cities.
Koo cautioned against taking the urbanization metaphor of biofilm growth too far but underscores the useful lessons that can result from studying the system holistically and by looking at the events under both close-up and bird’s eye views.
“It’s a useful analogy, but it should be taken with a grain of salt,” said Koo. “We’re not saying these bacteria are anthropomorphic. But taking this perspective of biofilm growth gives us a multiscale, multidimensional picture of how they grow that we’ve not seen before.”
The study, “Dynamics of Bacterial Population Growth in Biofilms Resemble Spatial and Structural Aspects of Urbanization,” was published by Nature Communications.
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