Three-dimensional architecture of Vibrio cholera biofilms.

Microbes That Are out of Place Inspired by Lord Chesterfield, anthropologist Mary Douglas noted that what is classified as dirt in a given society is matter that is considered out of place. From this premise, Douglas went on to an analysis of ritual and religion, interrelations between perceptions of purity, contamination, defilement, and danger, and our anthropological need for symbolic boundary maintenance (1). (Judaic kosher dietary laws are wellknown examples of her analysis.) Douglas probably did not anticipate that these ideas may have an unexpected valence in the way we think about microbial communities. What happens when a microbe is “out of place” and what are the associated dangers? Because microbial communities are found in diverse terrestrial environments, from the earth to the ocean to the atmosphere to environmental niches in hosts, such as humans and other animals, they impact, transform, and sustain life as we know it on the planet. However, this ubiquity also gives plenty of opportunities for microbes to be found out of place, to adapt and precipitate diverse unexpected consequences. Staphylococcus epidermidis is normally an innocuous commensal microbe found on human skin, but it has also become the most common source of infections on implanted biomedical devices, such as vascular catheters (2). There is even evidence that its more virulent cousin, Staphylococcus aureus, became the “superbug” known as methicillin-resistant Staphyloccus aureus (MRSA) by acquiring the methicillin-resistance cassettes from S. epidermidis (2). Other examples of misplaced microbes that become dangerous or even lethal include Clostridium difficile infections in the gut, Pseudomonas aeruginosa infections in cystic fibrosis airways, and Vibrio cholera, the aquatic microbe that sometimes finds its way into a human host, and the subject of the present study by Drescher et al. in PNAS (3). Being out of place is not always bad: the commensal microbes in our gastro-intestinal tracts “train” our immune systems and allow us to digest vegetables. Engineered environmental microbes can degrade plant cell walls for generating biofuels. In current thinking, strategic management of microbial communities has the potential to impact diverse medical conditions, including asthma, diabetes, obesity, psychiatric illnesses, and (of course) infectious diseases (4, 5). Microbiomes can be targets for new drugs, but they can also be sources of new drugs (6), given the constant competition among community microbes in diverse environments. It is humbling that despite our long acquaintance, we have recognized only relatively recently how narrow our knowledge of microbial communities is. This knowledge gap is all the more keenly felt given the importance of microbes to current concerns in health, energy, the environment, and agriculture. In fact, the recently proposed Unified Microbiome Initiative seeks to address this need to understand microbiomes in a broad range of contexts (7, 8). We often do not know the precise compositions, roles, structures, interactions, and dynamics of microbial communities. One of the significant obstacles to progress is the general lack of appropriate tools. We need to have measurement technologies that can enable and speed up basic science discovery and translation to applications (9). Drescher et al. make an impressive contribution in this area, by visualizing 3D biofilms of V. cholera, and their intricate processes of formation (3).