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Ga-PpIX-Mediated Photodynamic Inactivation of Staphylococcus aureus Small-Colony Variants.

Badhu Prashanthika Sivasubramaniam1, Alexander Wei1

  • 1Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.

ACS Infectious Diseases
|October 29, 2025
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Summary
This summary is machine-generated.

Small-colony variants (SCVs) of Staphylococcus aureus, often found in persistent infections, are susceptible to antimicrobial photodynamic inactivation (aPDI) using a gallium porphyrin (Ga-PpIX) photosensitizer. This light-based therapy offers a promising new approach for treating difficult S. aureus infections.

Keywords:
SCVantimicrobialheminhydrogen peroxidephotodynamicstaphylococcal

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Area of Science:

  • Microbiology
  • Photomedicine
  • Antimicrobial Resistance

Background:

  • Small-colony variants (SCVs) of Staphylococcus aureus are associated with persistent and chronic infections.
  • SCVs exhibit increased tolerance to oxidative and antibiotic stress compared to wild-type strains.
  • Current treatment strategies for S. aureus SCVs are often limited due to their resilience.

Purpose of the Study:

  • To investigate the susceptibility of S. aureus SCVs to antimicrobial photodynamic inactivation (aPDI).
  • To evaluate the efficacy of a non-iron hemin analog, gallium porphyrin (Ga-PpIX), as a photosensitizer for aPDI against S. aureus SCVs.
  • To compare the aPDI susceptibility of different types of S. aureus SCVs (R-SCV, D-SCV, O-SCV) with wild-type S. aureus.

Main Methods:

  • Generation of S. aureus SCVs (R-SCV, D-SCV, O-SCV) under specific stress conditions (low H2O2, Fe-deficiency, oxacillin).
  • Treatment of S. aureus SCVs and wild-type strains with varying concentrations of Ga-PpIX and a 405 nm light source.
  • Quantification of bacterial viability using colony-forming units per milliliter (CFU/mL) post-aPDI treatment.
  • Flow cytometry analysis to characterize R-SCVs and their interaction with the ferric iron regulator (Fur).

Main Results:

  • S. aureus SCVs demonstrated significant susceptibility to Ga-PpIX-mediated aPDI, with reductions of up to 3-log CFU/mL.
  • R-SCVs, auxotrophic for hemin, were effectively inactivated at 1.5 μM Ga-PpIX.
  • D-SCVs showed even higher susceptibility, requiring only nanomolar levels of Ga-PpIX (0.06 μM) for a 3-log reduction.
  • O-SCVs, generated under oxacillin stress, were also susceptible to aPDI, potentially due to heightened reactive oxygen species (ROS) sensitivity.
  • Wild-type S. aureus cultured under standard conditions were largely unreceptive to the aPDI treatment.

Conclusions:

  • S. aureus SCVs can be effectively targeted and inactivated using Ga-PpIX-mediated aPDI.
  • The susceptibility of SCVs to aPDI varies depending on the SCV subtype and underlying resistance mechanisms.
  • Ga-PpIX-mediated aPDI presents a promising therapeutic strategy for combating persistent S. aureus infections, offering an alternative to conventional antibiotics.