Biosynthesis

  1. Bacterial metabolism results in products that are used for the synthesis of cellular constituents, like peptidoglycan, LPS, proteins, nucleic acids, etc..  You learned about the mechanisms of bacterial transcription of mRNA, DNA replication (including types of mutations that can occur), and translation of proteins in biochemistry.
  2. Since bacteria do not have a nuclear membrane, transcription and translation are coupled.
  3. The bacterial cytoplasmic membrane is the site for many of the functions carried out by specialized eukaryotic organelles, including electron transport and energy production.
  4. Synthesis of peptidoglycan occurs in 3 phases, each of which can be inhibited by various antibiotics:
    1. Precursor subunits are synthesized and assembled inside the cell
      • the antibiotics, fosfomycin and cycloserine, inhibit precursor synthesis in the cytoplasm.
    2. At the membrane the units are attached to the bactoprenol “conveyer belt”.
    1. The bactoprenol molecule translocates the subunits to the outside of the cell, where they are attached to the polysaccharide chain (the antibiotic, vancomycin, inhibits this polymerization reaction). Crosslinking of the tetrapeptide chains between the NAM-NAG glycan chains of peptidoglycan is catalyzed by enzymes called transpeptidases.  These enzymes are also called penicillin-binding proteins (PBP) because they are the target of β-lactam antibiotics, such as penicillin, which bind to them.  Transpeptidases are present in the cell membrane of Gram-positive and Gram-negative bacterial cells.
      • Bactoprenol is normally recycled; the antibiotic, bacitracin, inhibits the re-use of bactoprenol.

Teichoic acid is synthesized from precursors in a similar manner as peptidoglycan.

 

Lipopolysaccharide (LPS) Synthesis

    1. Lipid A and core portions are enzymatically synthesized at the inside surface of the cytoplasmic membrane.
    1. Repeating units of the O antigen are assembled on a bactoprenol molecule and transferred to a growing O antigen chain.
    1. The completed O antigen chain is transferred to the core lipid A structure.
    1. The LPS molecule is then translocated through adhesion sites to the outer surface of the outer membrane.

Photo by phylofigures

Frequently Asked Questions

What is bacterial metabolism and why is it important?

Bacterial metabolism refers to the chemical processes that occur within bacteria, allowing them to grow, reproduce, and maintain their cellular functions. This includes synthesizing cellular constituents like peptidoglycan and proteins. Understanding bacterial metabolism is crucial as it helps in identifying targets for antibiotics, which can inhibit specific bacterial processes.

How does the synthesis of peptidoglycan occur in bacteria?

Peptidoglycan synthesis in bacteria occurs in three phases: precursor synthesis in the cytoplasm, attachment to bactoprenol at the membrane, and polymerization outside the cell. Antibiotics like fosfomycin and vancomycin can inhibit different stages of this process, making peptidoglycan synthesis a key target for antibacterial treatments.

What role does bactoprenol play in bacterial cell wall synthesis?

Bactoprenol is a lipid molecule that acts as a 'conveyor belt' during bacterial cell wall synthesis. It transports peptidoglycan precursor subunits across the cytoplasmic membrane to the outside of the cell, where they are integrated into the cell wall. Bactoprenol’s recycling can be inhibited by the antibiotic bacitracin, disrupting cell wall synthesis.

How are transcription and translation different in bacteria compared to eukaryotes?

In bacteria, transcription and translation are coupled, meaning they occur simultaneously because bacteria lack a nuclear membrane. This is different from eukaryotes, where transcription (in the nucleus) and translation (in the cytoplasm) are separate processes. This coupling allows for faster protein synthesis in bacteria.

What are penicillin-binding proteins and why are they significant?

Penicillin-binding proteins (PBPs) are enzymes involved in the crosslinking of peptidoglycan chains during bacterial cell wall synthesis. They are targets for β-lactam antibiotics, such as penicillin, which bind to these proteins and inhibit their activity, preventing cell wall construction and leading to bacterial cell death.

What is the role of lipopolysaccharide (LPS) in bacteria?

Lipopolysaccharide (LPS) is a molecule found in the outer membrane of Gram-negative bacteria. It consists of lipid A, a core polysaccharide, and O antigen. LPS plays a crucial role in protecting bacteria from hostile environments and can trigger immune responses in humans. Understanding LPS synthesis can help in developing treatments against Gram-negative bacterial infections.

How do antibiotics like vancomycin affect bacterial cells?

Vancomycin is an antibiotic that inhibits the polymerization of peptidoglycan chains by preventing the addition of new subunits to the growing polymer. This disrupts the structural integrity of the bacterial cell wall, ultimately leading to cell lysis and death. It is particularly effective against Gram-positive bacteria.

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