deaths of five people. Clostridium tetani is another sporeformer. Its spores can remain dormant in the soil for years, but when they enter the anaerobic environment of an open wound, they can reactivate and cause tetanus.
Figure 3. Caulobacter crescentus is used as a model for the study of differentiated cell division. When these bacteria split, they give birth to two slightly different cells, one with a stem and the other with a flagellum.
Because spores are highly resistant to adverse conditions and can spread easily, it is hard to get rid of them; spores are therefore very dangerous. Take for example the bacterium Clostridium difficile. “C. diff," as it is commonly called, is part of the human intestinal microbiome and is highly resistant to most antibiotics. When a patient is treated with antibiotics, the normal intestinal microbiome changes, leaving the resistant C. difficile to dominate and cause severe colitis and diarrhea. These bacteria are capable of producing spores that can survive almost anywhere for years. Hence, they are becoming a more and more common cause of health care-associated infections, particularly in hospitals.
Figure 4. Bacillus anthracis. Under conditions of stress, some bacteria produce spores that contain the bacteria's complete DNA. Spores can survive indefinitely in nature until more favorable conditions trigger them to germinate and replicate normally again.
Bacteria also have lesser-known survival strategies. For example, some bacteria can halt their peptidoglycan synthesis in order to produce progeny that lack peptidoglycan and are not recognized by the immune system. These are called L-form bacteria, from the name of the English surgeon Joseph Lister. Like the mycoplasmas described earlier, they are resistant to many antibiotics and can survive in an infected host for a long time, even during treatment.
It is now possible to watch bacteria divide and to examine the location, the behavior, or the fate of some bacterial proteins. Indeed, new imaging technologies—particularly time-lapse microscopy and superresolution microscopy, both of which use various fluorescent markers—have made it possible to study bacteria in real time. One can observe the precise location of fluorescently linked bacterial proteins (such as the pole or site of division) and see whether they become more intense or disappear during bacterial growth. Combining these imaging techniques with microfluidics—the study of the flow of microquantities of liquids—allows for the real-time observation of bacterial behavior, for example, during changes in cultures or temperature.
Bacterial cell biology is a new discipline that will allow the understanding of bacterial physiology in previously unobtainable detail. It will undoubtedly result in understanding important issues such as the persistence of pathogenic bacteria or the proliferation of some bacteria in certain environments.
CHAPTER 3
The RNA Revolution
Genes of a bacterium—its genetic ID card that distinguishes it from other bacteria—are, like our own, carried by the DNA of its chromosome. Bacterial chromosomes are usually circular in shape. Generally, bacteria have a single chromosome, though some bacteria such as Vibrio cholerae have two, and other uncommon genera can have more. Borrelia, which is carried by ticks and causes Lyme disease, has many linear chromosomes.
Many bacteria, in addition to their main chromosomes, also have circular minichromosomes called plasmids. These chromosomes are not essential to bacterial multiplication but nevertheless may play a significant role in bacterial survival and pathogenicity.
The DNA of a chromosome or a plasmid is a two-stranded polymer. Each strand is a succession of nearly identical components called nucleotides, made of a base plus a sugar, that differ only in their base: A, T, G, or C (adenine, thymine, guanine, and cytosine). The two strands of the DNA twist around each other in a helical ladder owing to the affinity of A for T and of G for C. The genes situated along the chromosome are made up of hundreds, sometimes thousands, of nucleotides. They carry within them the information needed to synthesize proteins. In other words, these genes encode proteins. In between the genes are found “intergenic” sequences of nucleotides that do not encode proteins.
The DNA present in bacteria is either identically copied or “read.” In the first case, the process of replication, both strands of the DNA are duplicated exactly, to be passed on to the daughter cells during cell division. In the second case, during transcription, the information carried on one DNA strand is “read” by a mechanism that creates a similar but different molecule called a transcript RNA molecule, a messenger RNA (mRNA) (Fig. 5). It is called “messenger” because it carries a message from the chromosome that will allow the cell to make a protein. RNAs typically have only one strand of ribonucleotides composed of one base and one sugar, as in DNA, but the four bases in RNA are A, U (for uracil), G, and C. RNAs contain the sugar ribose (which gives RNA its name, ribonucleic acid), whereas DNA has deoxyribose (which likewise gives DNA its name, deoxyribonucleic acid).
Replication begins in the part of a chromosome called the origin of replication and moves in two directions along the chromosome. As the chromosome is composed of two strands of DNA, each is thus duplicated. Once replication begins, the whole chromosome is replicated. Transcription, in contrast, is a process that moves in one direction only. It can begin at any point in a chromosome but only “upstream” of the gene(s) being transcribed, in regions that François Jacob and Jacques Monod named promoters. Only certain regions of each DNA strand are transcribed onto RNA. The RNA transcript—the mRNA—is then read during translation.
Figure 5. Schematic representation of a double strand of DNA, of its transcribed messenger RNA (mRNA), and of the small protein encoded by the mRNA.
Translation is a fairly sophisticated process that is achieved by several bacterial actors and in particular a big machine called the ribosome. Ribosomes read the nucleotide sequence of the mRNA transcript by recognizing successive triplets of nucleotides or codons. Each of the 64 possible triplets of nucleotides (AUG, UAC, or ACC, for example) corresponds to one of the 20 amino acids that are the building blocks for proteins; thus each amino acid can be encoded by more than one codon. This genetic code is the same for all bacteria and most other organisms. Thus, from their DNA, bacteria produce RNA that is ultimately translated into proteins by this universal code. Bacteria produce thousands of mRNAs, each of which produce proteins.
The results that led François Jacob, André Lwoff, and Jacques Monod to their 1965 Nobel Prize in Physiology or Medicine concerned the discovery that several successive genes, generally involved in the same physiological function, are transcribed together from a single promoter in a single mRNA and thus form a cluster of coregulated genes that they termed an operon.
Transcription is not a permanent process. It depends on many environmental factors (such as pH or temperature). It also depends on bacterial factors. In the simplest situation, transcription is regulated by
