Chapter Introduction

20: The Regulation of Gene Expression in Bacteria

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  • 20.1 Transcriptional Regulation

  • 20.2 Beyond Transcription: Control of Other Steps in the Gene Expression Pathway

  • 20.3 Control of Gene Expression in Bacteriophages

MOMENT OF DISCOVERY

Bonnie Bassler

For me, science is all about those moments of clarity, when years of struggling to figure something out finally pay off with an incredible insight about how nature works. I am fascinated by how bacterial cells communicate with each other in the regulatory process known as quorum sensing. Quorum-sensing bacteria make, release, and detect chemical signal molecules that increase in concentration in proportion to increasing cell population numbers. Cells respond to these chemicals with synchronous population-wide changes in behavior; community behavior allows bacteria to carry out tasks that could never be accomplished if a single bacterium acted alone. We suspect that the evolution of cell-cell communication in bacteria is one of the first steps in the development of multicellular organisms.

Vibrio harveyi is a bioluminescent gram-negative marine bacterium that regulates light production in response to two distinct chemical “words,” or autoinducers. As a new professor, I wanted to answer a question that had baffled the field for several years: Why does V. harveyi need two chemical signals for communication, when one should be sufficient? The identity of one autoinducer, AI-1 (autoinducer-1), had been determined, but the other, AI-2, remained an enigma. Our lab cloned the gene that encodes the protein responsible for synthesizing AI-2, and sequenced the gene. At that time, there were no extensive databases of bacterial genome sequences available, only partial genomes for 40 or 50 different bacterial species. Nonetheless, we searched the incomplete database for a match to our sequence.

I recall sitting in front of the computer as the name of bacterium after bacterium scrolled up the screen. In the end, every single bacterium in the database contained a gene that closely matched our sequence! I realized at that moment that the bacteria were talking across species. The mysterious autoinducer AI-2 was, in fact, a chemical that enables different species to communicate with each other, a system that would obviously be very useful in natural settings where many different kinds of bacteria live together. This discovery changed the entire course of research in the field and led me to focus over the past decade on the mechanisms of interspecies communication.

—Bonnie Bassler, on her discovery of interspecies quorum sensing

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As we discussed in Chapter 19, cells typically express just a subset of their genes at any given time. Some gene products are synthesized in large amounts, and many others in only small amounts or not at all, depending on the needs of the cell. For example, in bacteria, proteins directly involved in DNA replication and protein biosynthesis are required continuously during active growth, whereas proteins that mediate DNA repair or the metabolism of rare sugars may be needed only sporadically. Furthermore, requirements for many gene products change over time. The need for enzymes that participate in various metabolic pathways increases or decreases as nutrient types and levels change. The regulation of gene expression is essential for making optimal use of available energy and for enabling cells to adapt to a wide variety of environmental changes.

Much of what we know about gene regulation comes from studies that focused, at least initially, on bacterial systems. Microbes are masters at regulating gene expression, due to their need to adapt quickly to changing conditions. Thus they have provided investigators with many opportunities to discover fundamental mechanisms that, as it turns out, also characterize the gene regulatory pathways in humans, plants, and other eukaryotes. Recall that there are seven points in the flow of biological information where regulation can take place (see Figure 19-1). Not all of these occur in bacteria, however, due to the absence or rarity of certain of the processes, such as pre-mRNA splicing, in bacterial cells.

In this chapter, we focus on some of the central aspects of bacterial gene regulation by examining specific examples. Although much of the classic research in this field concentrated on the regulation of transcription, more recent investigations have revealed that other stages of gene expression, notably translation, provide bacterial cells with exquisite tools to fine-tune their protein levels. In addition to the roles of regulatory proteins in altering gene expression levels, regulatory RNAs are ubiquitous in controlling how, when, and where proteins are made. The multiple levels of gene regulation observed in the bacteriophage λ (λ phage) infection and replication cycle set the stage for explaining the kinds of complex regulatory interactions found in eukaryotes—the topic of Chapters 21 and 22.