Small but Mighty: Cell Size and Bacteria

Our view of bacteria is overwhelmingly shaped by their diminutive nature. The most ancient of organisms, their very presence was not appreciated until the 17th century with the invention of the microscope. Initially, viewed as “bags of enzymes,” recent advances in imaging, molecular phylogeny, and, most recently, genomics have revealed incredible diversity within this previously invisible realm of life. Here, we review the impact of size on bacterial evolution, physiology, and morphogenesis.Humanity has always experienced the impact of microorganisms, most obviously through their ability to cause devastating disease. For the vast majority of human history, we were unaware of their presence, much less the fundamental microbial processes to which we owe our existence: from the production of energy by our ancient bacterial endosymbionts (the mitochondria) to the generation of oxygen in our atmosphere. Despite their astounding global abundance (∼10³⁰ cells) and their substantial contribution to the total biomass of planet earth (Whitman et al. 1998; Kallmeyer et al. 2012), our inability to see these tiny life forms shrouded their nearly limitless diversity in mystery. It was not until the 17th century, with the careful observations and reports of Anton van Leeuwenhoek, that we became aware of this previously invisible world on and around us. Today, we know that there are more bacteria living in our intestinal tract than stars in the Milky Way galaxy (and that they far outnumber all the people who have ever lived). We also know now that we thrive because of their metabolic support. Although less than 1% of bacteria can be cultured readily in the laboratory (Amann et al. 1995), the biochemical versatility among these tiny creatures exceeds that of the plants, animals, and fungi combined (Pace 1997).Anton van Leeuwenhoek’s illustrations in a letter to the Royal Society of London in the late 17th century provide one of the earliest records of bacterial cell form (Dobell 1960). Viewed through a single lens, Leeuwenhoek pioneered studies of the human microbiome, describing motile bacilli, cocci, and spirochetes he found in scrapings taken from between his teeth (and the teeth of others). This triumph was made possible by incomparable curiosity, lens construction, and exceptional lighting. The simple cellular structure and glassy nature of most unstained bacteria viewed with a light microscope generated little interest in bacterial cell biology with the exception of objects of unusual contrast, such as endospores described by Robert Koch and the wonderfully colorful and large cyanobacteria. The bacterial nature of the latter was itself only appreciated late in the 20th century (Oren 2004). For the most part, bacteria were viewed as primitive “bags of enzymes” until the 1990s, when the complexity of bacterial subcellular structure and regulators of cell reproduction finally began to emerge. Tools and reagents developed for eukaryotic cell biology (e.g., stains for DNA, membranes, and fluorescent protein tags), once applied to bacterial cells, revealed astonishing insights including the specific and even dynamic localization patterns of proteins, and the accuracy of chromosome organization.