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Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
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Bacterial and archaeal cells exhibit remarkable diversity in shape and structure, critical in their adaptability and functionality. Among bacteria, the most commonly observed shapes include cocci and bacilli. Cocci are spherical and may exist singly or in groupings such as pairs (diplococci), chains (streptococci), clusters (staphylococci), or tetrads. Bacilli, in contrast, are rod-shaped and can also occur as single cells, in pairs, or chains, depending on their environmental and genetic...
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Application of Genetically Encoded Fluorescent Nitric Oxide (NO&#8226;) Probes, the geNOps, for Real-time Imaging of NO&#8226; Signals in Single Cells
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Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells

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Nitric Oxide-Induced Morphological Changes to Bacteria.

Huan K Nguyen1, Samantha L Picciotti1, Magdalena M Duke1

  • 1Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

ACS Infectious Diseases
|October 13, 2023
PubMed
Summary
This summary is machine-generated.

Nitric oxide (NO) donors damaged Gram-negative bacteria cell walls, with slow-release donors causing more harm. Positively charged dendrimers were needed to penetrate Gram-positive bacteria cell walls.

Keywords:
ESKAPE pathogensNO-releasing dendrimerantimicrobial resistancemorphological Changesnitric oxidepositively charged quaternary ammonium

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Area of Science:

  • Microbiology
  • Biochemistry
  • Materials Science

Background:

  • Antimicrobial resistance is a global health crisis requiring novel therapeutic strategies.
  • Nitric oxide (NO) plays a role in pathogen response and has potential antimicrobial applications.
  • Exogenous NO donors offer a promising avenue for developing new anti-infective treatments.

Purpose of the Study:

  • To investigate the impact of nitric oxide (NO) delivered by various exogenous donors on bacterial cell envelopes.
  • To assess how NO donor architecture influences bacterial wall degradation in Gram-negative and Gram-positive pathogens.
  • To evaluate the efficacy of different NO delivery systems against antibiotic-resistant strains.

Main Methods:

  • Microscopy and fluorescence-based techniques were used to examine bacterial cell envelopes after NO treatment.
  • Transmission electron microscopy (TEM) visualized structural changes in bacterial cell walls and membranes.
  • Depolarization assays measured cell wall permeation in response to NO donors.

Main Results:

  • NO donors caused significant membrane damage and cell wall disruption in Gram-negative bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa).
  • Slow NO release (t1/2 = 120 min) from small molecules resulted in greater damage to Gram-negative bacteria compared to rapid release (t1/2 = 24 min).
  • NO treatment did not drastically alter Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecium) morphology, but QA-modified dendrimers penetrated their cell walls.

Conclusions:

  • The architecture of NO donors significantly impacts their efficacy against bacterial cell envelopes.
  • Slow-releasing NO donors are more effective at degrading Gram-negative bacterial cell walls.
  • Positively charged NO-releasing dendrimers are uniquely capable of penetrating the peptidoglycan layer of Gram-positive bacteria, offering a potential strategy for treating these infections.