Related Experiment Video
Updated: Oct 16, 2025

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity
Miki Kawada-Matsuo1, Mi Nguyen-Tra Le1, Hitoshi Komatsuzawa1
1Department of Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Abstract:
Staphylococcus aureus is a bacterium that mainly colonizes the nasal cavity and skin. To colonize the host, it is necessary for S. aureus to resist many antibacterial factors derived from human and commensal bacteria. Among them are the bacteria-derived antimicrobial peptides (AMPs) called bacteriocins. It was reported that some two-component systems (TCSs), which are signal transduction systems specific to bacteria, are involved in the resistance to several bacteriocins in S. aureus. However, the TCS-mediated resistance is limited to relatively low concentrations of bacteriocins, while high concentrations of bacteriocins still exhibit antibacterial activity against S. aureus. To determine whether we could obtain highly bacteriocin-resistant mutants, we tried to isolate highly nisin A-resistant mutants by exposing the cells to sub-minimum inhibitory concentrations (MICs) of nisin A. Nisin A is one of the bacteriocins produced by Lactococcus lactis and is utilized as a food preservative worldwide. Finally, we obtained highly nisin A-resistant mutants with mutations in one TCS, BraRS, and in PmtR, which is involved in the expression of pmtABCD. Notably, some highly resistant strains also showed increased pathogenicity. Based on our findings, this review provides up-to-date information on the role of TCSs in the susceptibility to antibacterial peptides. Additionally, the mechanism for high antimicrobial peptides resistance and its association with pathogenicity in S. aureus is elucidated.
Insights
Highly nisin A-resistant Staphylococcus aureus mutants were developed using specific mutations in two-component systems (TCSs) and PmtR. Some resistant strains exhibited increased pathogenicity, highlighting a link between resistance and virulence.
Area of Science:
- Microbiology and Molecular Biology
- Bacterial Pathogenesis
- Antimicrobial Resistance
Background:
- Staphylococcus aureus colonizes human hosts by resisting antibacterial factors, including bacteriocins.
- Two-component systems (TCSs) in S. aureus confer resistance to bacteriocins, but only at low concentrations.
- Nisin A, a bacteriocin used as a food preservative, is produced by Lactococcus lactis.
Purpose of the Study:
- To isolate highly nisin A-resistant Staphylococcus aureus mutants.
- To investigate the genetic basis of high-level bacteriocin resistance.
- To explore the association between antimicrobial peptide resistance and bacterial pathogenicity.
Main Methods:
- Exposure of S. aureus to sub-inhibitory concentrations of nisin A to select for resistant mutants.
- Identification of mutations in identified resistant strains.
- Assessment of pathogenicity in highly resistant S. aureus isolates.
Main Results:
- Isolation of highly nisin A-resistant S. aureus mutants.
- Identification of mutations in the BraRS two-component system (TCS) and PmtR regulator in resistant strains.
- Observation of increased pathogenicity in some highly nisin A-resistant S. aureus strains.
Conclusions:
- The BraRS TCS and PmtR play crucial roles in conferring high-level resistance to nisin A in S. aureus.
- High-level antimicrobial peptide resistance in S. aureus can be associated with enhanced pathogenicity.
- Findings provide insights into TCS-mediated resistance mechanisms and their link to virulence in S. aureus.
Related Concept Videos
Defense Against Bacterial Pathogens
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...
Gene Regulation in Microbial Communities: Quorum Sensing
Development of Antibiotic Resistance
Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Antibiotic Selection
Gram-negative Bacterial Protein Secretion Systems

