and multiply and invade different parts of the body such as the throat (Streptococcus), the lungs (Legionella), the intestines (Salmonella), or the nose and pharynx (Pneumococcus). Bacteria often can establish an infection only if the host’s immunity is weakened by fatigue by a viral or other infection (such as pneumococcal infections that often follow respiratory tract inflammation due to influenza), by medical treatment (such as immune suppression due to chemotherapy), or by a genetic mutation.
The importance of the genetic context with regard to a host’s susceptibility to infection is now the subject of extensive studies by scientists around the world. The laboratory led by Jean-Laurent Casanova is a strong proponent of the hypothesis that disease can be or is linked to the host’s genetics. These investigators have found evidence for genetic predisposition to several illnesses, for example, susceptibility to infection with low-pathogenicity mycobacterial strains including BCG, the live attenuated strain of Mycobacterium bovis used to vaccinate against tuberculosis. Some children have a defect in one of the genes coding for interferon or for interferon signaling, which can result in unanticipated and sometimes fatal illness after vaccination.
Throughout this book, we will learn that bacteria, both pathogenic and nonpathogenic, are living organisms with a range of diverse properties, some of which are quite unexpected. With their unique capacity to produce vital compounds or to transform or eliminate other compounds, bacteria contribute constantly to the everyday lives of their hosts and to the balance of the ecosystems where they live.
CHAPTER 2
Bacteria: Highly Organized Unicellular Organisms
Bacteria seem to be very simple cells, having neither a nucleus nor internal organelles as in animal or plant cells, but they actually have a highly structured internal organization. Their shape is very precise and their content is well organized. Each protein or group of proteins has its specific location, from one generation to the next.
Most bacteria have an outer layer consisting of a thin membrane that is covered by a cell wall made up of pep-tidoglycan, which gives each bacterium its shape and rigidity and allows it to survive drastic differences between its interior and its exterior environment, including differences in temperature, pH, and salinity. Some bacteria also have a second external membrane and also a capsule.
Bacteria are often classified into two categories, Gram positive and Gram negative. These terms derive from the staining technique developed by Hans Christian Gram, in which a purple dye binds to the pep-tidoglycan in bacteria that have a thick cell wall but no external membranes and is negative in all other cases. The Gram stain uses crystal violet, a purple stain that binds to the peptidoglycan in bacterial cell walls. The process concludes with a wash with a decolorizing agent and counterstain. Bacteria that have cell walls but no external membranes retain the stain (yielding a purple-colored “positive” cell) while bacteria with external membranes and a thinner cell wall do not retain the crystal violet (yielding pink-colored “negative” cells).
Mycoplasma
Mycoplasmas, of the genus Mycoplasma, are bacteria that have cell membranes but lack a cell wall. These relatively small bacteria have historically been difficult to locate and identify because the principal bacterial identification method, the Gram stain, is based on identification of the peptidoglycan in bacterial cell walls. Our inability to detect Mycoplasma has been a problem because many mycoplasmas, which are in most cases commensals (i.e., nonpathogenic) in the respiratory tract or vagina, can be responsible for sexually transmitted infections. Also, because these organisms have no cell walls, they are not affected by antibiotics that target peptidoglycan. Mycoplasmas have some of the smallest bacterial genomes, and the chromosome of Mycoplasma genitalium was the first to be synthesized by means of synthetic biology tools.
Flagella and other appendages
Flagella are found on the surface of bacteria. They are long helical filaments connected to small rotary motors that allow the bacteria to move and spread out in fluid environments. Hairlike appendages known as pili are also found on the surface of some bacteria. Pili allow bacteria to adhere to biological and abiotic surfaces or even to aggregate. Curli, similar to pili, are involved in adherence to surfaces and bacterial aggregation. They closely resemble the aggregating “amyloid” fibers found in the brains of Alzheimer patients.
The shape of bacteria is maintained by their cell wall, but their size depends on the volume of their interior, which expands during bacterial growth. Bacteria have a highly organized internal architecture thanks to molecules that are similar to those found in human or plant cells. It was discovered that bacteria even have skeletons, spiral-shaped cytoskeletons made of actin that are involved in the localization and activation of enzymes that create peptidoglycan and are crucial for cell division.
Bacterial shape and division: proteins similar to actin and tubulin in eukaryotes
Bacillus-type (rod-shaped) bacteria and their cell walls grow depending on the growth medium composition. Growth of the peptidoglycan, and thus also of the cell wall, is controlled by MreB, a protein anchored to the membrane that is similar to the protein actin in eukaryotes. MreB forms a sort of spiral structure that gives bacilli their elongated form. A protein known as crescentin is responsible for the crescent shape of Caulobacter cells. Bacterial growth has a limit. Once a bacterium reaches a certain size, it splits. This is a highly precise process that uses at least two other molecules similar to actin and tubulin, proteins that were once thought to be present only in eukaryotes. In addition, when a bacterium divides, every vital element of the bacterium, including the chromosome (more specifically the DNA), is duplicated and shared between the two resulting daughter cells. At the final phase of division, the key step in the separation of two daughter cells involves another actin-like protein, FtsA, which attaches to the site of division, FtsZ, a protein similar to the tubulin protein in eukaryotic cells. ParM is another protein similar to eukaryotic actin that is involved in the distribution of plasmid DNA between daughter cells.
Most bacteria produce two apparently identical daughter cells. However, some, such as Caulobacter crescentus, do not. Caulobacter is an aquatic bacterium that has become an impressive model for asymmetrical cell division (Fig. 3). A Caulobacter cell about to divide is immobile, attached by a short stem to a surface such as a rock or the ocean bottom. The unattached end generates a mobile daughter cell that uses a flagellum to propel itself away from the still-attached daughter cell, which will continue to grow and split off more daughters. The mobile cell eventually loses its flagellum and grows a stem that it uses to attach itself to a surface, where it will grow and eventually split off daughter cells of its own.
Are bacteria immortal? Do they have strategies for survival? When stressed by conditions such as desiccation or nutrient deficiency, some bacteria reproduce by forming spores. These are a type of dormant cell that is extremely resistant to heat, cold, dryness, and even some antiseptics. Spores allow bacteria to persist for years or even centuries—and to disseminate (Fig. 4). When a spore arrives in an appropriate environment, it can germinate and resume a normal binary cell division.
Not all bacteria produce spores, but several that do are considered some of the most dangerous to humans. In late 2001 in the United States, anthrax spores (spores of Bacillus anthracis) sent through the mail as an act of bioterrorism caused skin, intestinal,
