Microbial Gene Regulation and Viral Pathogenesis: Study Notes

Gene Regulation in Prokaryotes

Overview of Prokaryotic Gene Regulation

Gene regulation in prokaryotes is essential for adapting to environmental changes and efficiently utilizing resources. Unlike eukaryotes, prokaryotes often regulate genes at the transcriptional level, allowing rapid responses to stimuli.

• Regulation at Prokaryotic Level: Bacteria regulate mRNA translation through multiple mechanisms, primarily at the transcriptional level.

• Gene Arrangement: Bacterial and archaeal genomes differ from eukaryotes, often lacking introns and featuring operons.

• Operons: Two or more genes transcribed under the control of a single promoter region, resulting in a polycistronic mRNA.

• Promoters and Operators: Promoters are DNA sequences where RNA polymerase binds; operators are regions where regulatory proteins bind to influence transcription.

DNA Binding Proteins and Regulatory Sequences

Regulatory proteins interact with specific DNA sequences to control gene expression.

• DNA Binding Proteins: Proteins that interact with nucleic acids to regulate transcription.

• Inverted Repeats: DNA sequences arranged in opposite orientations, often serving as binding sites for regulatory proteins.

• Homodimeric Proteins: Regulatory proteins often function as homodimers, with each polypeptide binding to an inverted repeat.

Transcriptional Control Mechanisms

Transcriptional regulation involves both positive and negative control mechanisms, mediated by small molecules and regulatory proteins.

• Positive Control: Activator proteins enhance transcription by facilitating RNA polymerase binding.

• Negative Control: Repressor proteins inhibit transcription by blocking RNA polymerase binding.

• Inducers and Corepressors: Small molecules that modulate the activity of regulatory proteins. Inducers promote gene expression, while corepressors inhibit it.

• Examples:

  • Lac Operon: Negative control; lac repressor binds operator to block transcription. Inducer (allolactose) inactivates repressor, allowing transcription.

  • Arginine Operon: Negative control; arginine acts as a corepressor, enabling the repressor to block transcription when arginine is abundant.

  • Maltose Operon: Positive control; activator protein binds in presence of maltose, recruiting RNA polymerase.

Summary Table: Types of Gene Regulation in Prokaryotes

Type	Regulatory Protein	Effector Molecule	Effect on Transcription	Example
Negative Control (Inducible)	Repressor	Inducer	Inducer inactivates repressor, transcription proceeds	Lac operon
Negative Control (Repressible)	Repressor	Corepressor	Corepressor activates repressor, transcription blocked	Arginine operon
Positive Control	Activator	Inducer	Activator recruits RNA polymerase, transcription proceeds	Maltose operon

Gene Regulation in Archaea

Archaeal Gene Regulation

Gene regulation in Archaea shares similarities with both bacteria and eukaryotes. Promoters and regulatory proteins control transcription, but the mechanisms can be more complex.

• Promoters: Archaeal promoters are more similar to eukaryotic promoters but use regulatory strategies akin to bacteria.

• Regulons: Sets of operons and genes under the control of a single regulatory protein.

Noncoding RNA and Post-Transcriptional Regulation

Noncoding RNA (ncRNA)

Noncoding RNAs are RNA molecules that are not translated into proteins but play crucial roles in gene regulation.

• Types: Includes rRNA, tRNA, small regulatory RNAs (sRNAs), and signal recognition particle RNA.

• Small RNA (sRNA): 40-400 nucleotides; regulate gene expression by base pairing with mRNAs, affecting translation and stability.

Mechanisms of Post-Transcriptional Regulation

• Altering mRNA Translation: sRNAs can block or open ribosome binding sites, change mRNA secondary structure, or target mRNA for degradation.

• mRNA Stability: sRNAs can increase or decrease mRNA degradation rates.

• Inhibition of Translation: sRNAs prevent ribosome binding, inhibiting protein synthesis.

• Promotion of Degradation: sRNAs recruit ribonucleases to degrade target mRNAs.

Two-Component Regulatory Systems and Quorum Sensing

Two-Component Systems

These systems allow bacteria and archaea to sense and respond to environmental changes.

• Components: Sensor kinase (detects signal) and response regulator (mediates response).

• Function: Phosphorylation cascade transmits signal, altering gene expression.

Quorum Sensing

Quorum sensing is a mechanism by which bacteria coordinate gene expression based on population density.

• Signaling Molecules: Autoinducers accumulate as cell density increases.

• Threshold: When a minimum concentration is reached, gene expression changes collectively.

• Applications: Biofilm formation, virulence, and pathogenesis.

• Positive Feedback: Signaling molecules activate genes necessary for their own production.

Viral Pathogenesis: Hepatitis and Influenza

Hepatitis Viruses

Hepatitis refers to liver inflammation caused by viral or bacterial infections. Several hepatitis viruses differ in transmission, severity, and outcomes.

• Hepatitis A: Infectious, mild, rare severe cases; first vaccine given in childhood.

• Hepatitis B: Acute and severe; can cause liver failure and death; vaccine available.

• Hepatitis C: Mild disease, can progress to chronic infection.

• Hepatitis D: Defective virus; requires co-infection with hepatitis B.

• Hepatitis E: Acute, self-limiting, variable severity.

Prevention: Vaccines are available for hepatitis A and B. Incidence of hepatitis A, B, and C has decreased significantly in the US in the last 20 years.

Viral Evasion of Host Immunity

• Immune Evasion: Viruses can disrupt pattern recognition receptors (PRRs) to avoid detection.

• Hepatitis C: Infects cells, shuts down PRR signaling, recruits immune cells, and allows the virus to remain hidden and replicate.

• Chronic Infection: Prolonged infection can exhaust the immune system, especially in the liver.

Influenza Virus

Influenza is a respiratory virus characterized by its ability to undergo genetic shift, leading to new strains and pandemics.

• Key Proteins: Hemagglutinin (attachment to host cells) and neuraminidase (release of new virions).

• Hemagglutinin: Binds to epithelial surface receptors, allowing viral entry.

• Neuraminidase: Cleaves sialic acid, facilitating viral release from host cells and reducing mucus viscosity.

• Neuraminidase Inhibitors: Prevent spread of virus but do not stop infection entirely.

• Genetic Shift: Influenza is unique among viruses in its ability to undergo genetic shift, resulting in major antigenic changes.

Additional Concepts

Allosteric Inhibition

Allosteric inhibition involves the binding of a molecule at a site other than the enzyme's active site, altering enzyme activity.

• Mechanism: Binding at the allosteric site changes the shape of the active site, preventing substrate binding and enzymatic function.

• Types: Competitive, noncompetitive, and uncompetitive inhibition.

Pho System

The Pho system is a global regulatory system in bacteria that senses and responds to phosphate availability.

• Components: Two-component system involving sensor kinase and response regulator.

• Function: Regulates genes involved in phosphate metabolism.

Glossary of Key Terms

• Operon: A cluster of genes under the control of a single promoter, transcribed as a single mRNA.

• Regulon: A collection of operons and genes regulated by the same regulatory protein.

• Repressor: Protein that binds to operator sequences to block transcription.

• Activator: Protein that enhances transcription by facilitating RNA polymerase binding.

• Inducer: Small molecule that inactivates a repressor or activates an activator.

• Corepressor: Small molecule that activates a repressor protein.

• Autoinducer: Signaling molecule used in quorum sensing.

• Hemagglutinin: Influenza virus protein responsible for binding to host cells.

• Neuraminidase: Influenza virus protein that facilitates viral release from host cells.