Aromatic Compound-Dependent Staphylococcus aureus Is Safe in a Nasal Colonization Leukopenic Murine Model

Area of Science:

• Microbiology
• Infectious Diseases
• Bacterial Genetics

Background:

• Staphylococcus aureus nasal carriage is a significant risk factor for infections in vulnerable populations.
• Previous research indicated that attenuated S. aureus mutants could reduce pathogenic S. aureus colonization via bacterial interference.
• Developing safe and effective strategies to prevent S. aureus infections in healthcare settings is crucial.

Purpose of the Study:

• To construct and assess the safety of a ΔaroA mutant of S. aureus for potential use in preventing pathogenic S. aureus colonization.
• To develop a method for discriminating the engineered mutant from clinical S. aureus isolates.

Main Methods:

• Construction of a ΔaroA mutant (RD17) of S. aureus.
• Determination of the mutant's virulence using LD50 assays in mice.
• Evaluation of mutant's colonization and safety in leukopenic mice.
• Utilizing SmaI pulsed-field gel electrophoresis (PFGE) typing for strain discrimination.

Main Results:

• The ΔaroA mutant RD17 exhibited significantly reduced virulence (LD50: 3.2 × 10^6 CFU) compared to the parental strain (LD50: 2.2 × 10^3 CFU).
• RD17 demonstrated safe colonization in mice, maintaining low levels in nasal passages irrespective of the host's immune status.
• PFGE typing successfully differentiated the RD17 mutant from nasal colonizing and osteomyelitis S. aureus isolates.

Conclusions:

• The ΔaroA mutant RD17 is a safe candidate for artificial nasal colonization, showing reduced pathogenicity and stable low-level growth.
• PFGE typing provides a reliable method to distinguish the engineered mutant from endogenous S. aureus strains, crucial for clinical and research settings.
• This attenuated S. aureus mutant holds promise as a tool to mitigate S. aureus infections in hospitalized patients.