Antibacterial agents and release of periplasmic pertussis toxin from Bordetella pertussis

K A Craig-Mylius1, A A Weiss

  • 1Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524, USA.

Insights

Antimicrobial agents targeting bacterial membranes, not protein synthesis or transcription, inhibited pertussis toxin release from Bordetella pertussis. This suggests membrane integrity is crucial for toxin secretion.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Pertussis toxin is a key virulence factor secreted by Bordetella pertussis.
  • The toxin accumulates in the periplasm before secretion.
  • Understanding the secretion mechanism is vital for developing targeted therapies.

Purpose of the Study:

  • To investigate the effects of various antimicrobial agents on the release of preformed pertussis toxin.
  • To determine the role of protein synthesis, transcription, and membrane integrity in toxin secretion.

Main Methods:

  • Bordetella pertussis cultures were treated with antibiotics inhibiting protein synthesis (erythromycin, chloramphenicol), transcription (rifampin), cell wall biosynthesis (cefoperazone, piperacillin), or magnesium sulfate.
  • The impact of membrane-affecting agents (polymyxin B, lidocaine, procaine, ethanol) on toxin release was assessed.

Main Results:

  • Antibiotics targeting protein synthesis, transcription, or cell wall biosynthesis did not prevent pertussis toxin release.
  • Magnesium sulfate inhibited toxin gene transcription but not the release of preformed toxin.
  • Agents disrupting bacterial membranes significantly inhibited the release of preformed pertussis toxin.

Conclusions:

  • New protein synthesis is not required for the secretion of preformed pertussis toxin.
  • A functional bacterial membrane complex is essential for the release of pertussis toxin.
  • Targeting bacterial membrane integrity may represent a novel strategy to inhibit pertussis toxin secretion.

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
Bacterial Toxins01:12

Bacterial Toxins

Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
Diphtheria01:28

Diphtheria

Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific β-corynephage. This phage...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...