Related Experiment Video

Updated: Nov 2, 2025

High-throughput Screening of Chemical Compounds to Elucidate Their Effects on Bacterial Persistence
07:25

High-throughput Screening of Chemical Compounds to Elucidate Their Effects on Bacterial Persistence

Published on: February 23, 2021

4.3K

Macrophage-Produced Peroxynitrite Induces Antibiotic Tolerance and Supersedes Intrinsic Mechanisms of Persister

Jenna E Beam1, Nikki J Wagner1, John C Shook1

  • 1Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.

Infection and Immunity
|June 7, 2021
PubMed

Insights

Host immune cells, specifically macrophages, induce antibiotic tolerance in Staphylococcus aureus via peroxynitrite. This finding suggests targeting host responses could resensitize bacteria to antibiotics.

Area of Science:

  • Microbiology
  • Immunology
  • Infectious Diseases

Background:

  • Staphylococcus aureus is a major cause of persistent human infections.
  • Antibiotic tolerance in persister cells contributes to treatment failures.
  • Macrophages are a key host niche during S. aureus bacteremia.

Purpose of the Study:

  • To identify the host-derived factors mediating antibiotic tolerance in S. aureus within macrophages.
  • To investigate the role of oxidative burst products in S. aureus antibiotic tolerance.
  • To determine if host-induced tolerance overrides bacterial persister formation mechanisms.

Main Methods:

  • Exposure of S. aureus clinical isolates to activated macrophages.
  • Analysis of bacterial antibiotic tolerance following host cell internalization.
  • Identification of host-derived reactive nitrogen species involved in tolerance.

Main Results:

  • Host-derived peroxynitrite, a product of superoxide and nitric oxide, is the primary mediator of S. aureus antibiotic tolerance within macrophages.
  • All tested S. aureus clinical isolates showed similar enrichment for antibiotic tolerance after macrophage internalization, irrespective of in vitro persister levels.
  • Host interaction significantly enhances S. aureus antibiotic tolerance, potentially masking intrinsic bacterial persister formation strategies.

Conclusions:

  • Bacterial interaction with the host immune environment, particularly macrophages, is critical for inducing antibiotic tolerance.
  • Peroxynitrite generated by host macrophages is a key factor driving S. aureus antibiotic tolerance.
  • Modulating host immune responses may offer novel therapeutic strategies to overcome antibiotic tolerance in S. aureus infections.
Keywords:
Staphylococcus aureusantibiotic tolerancemacrophagesperoxynitritepersister cellsreactive oxygen species

More Related Videos

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes07:44

Time-Lapse Epifluorescence Microscopy Imaging of Pseudomonas aeruginosa and Staphylococcus aureus Heterogeneous Phenotypes

Published on: February 14, 2025

1.2K
Population and Single-Cell Analysis of Antibiotic Persistence in Escherichia coli12:29

Population and Single-Cell Analysis of Antibiotic Persistence in Escherichia coli

Published on: March 24, 2023

2.4K

Related Concept Videos

Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
1.7K
Development of Antibiotic Resistance01:30

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
688
Antibiotic Selection00:57

Antibiotic Selection

Overview
56.9K
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,...
180
Oxygen Requirements and Growth Patterns01:29

Oxygen Requirements and Growth Patterns

Microorganisms exhibit diverse oxygen requirements and growth patterns driven by their metabolic strategies and environmental adaptations. Oxygen, while essential for many organisms, can also be toxic under certain conditions, shaping how microorganisms grow and survive.Oxygen Requirements of MicroorganismsMicroorganisms are classified based on their ability to use or tolerate oxygen:● Obligate aerobes like Mycobacterium tuberculosis need oxygen for energy production, as it serves as the...
746
Transduction01:16

Transduction

Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
417