Staphylococcus aureus small colony variants originating from the lower respiratory tract are associated with...

Staphylococcus aureus small colony variants (SCVs) are responsible for pulmonary infections in cystic fibrosis patients globally, including regions such as Europe and the Americas.There is currently a lack of research in China on persistent pulmonary infections caused by S. aureus SCVs. In this study, we aimed to investigate the clinical and pathogenic characteristics of S. aureus SCVs in the lower respiratory tract of patients with Pseudomonas aeruginosa pneumonia.

From October 2024 to January 2026, normal phenotype S. aureus and S. aureus SCVs (characterized by small, slow-growing colonies with atypical morphology) were collected from lower respiratory tract specimens at two tertiary grade A hospitals in Fuzhou. Antibiotic susceptibility testing was performed using the VITEK^® 2 Compact system. Molecular characteristics were analyzed by multilocus sequence typing (MLST), virulence genes were screened by PCR, and biofilm formation capacity was assessed using a microtiter plate assay. Pathogenicity was evaluated through serum killing assays and a mouse pulmonary infection model. Patient characteristics were analyzed using the hospital information system.

A total of 46 S. aureus SCVs (2.2%) were isolated from 2130 lower respiratory tract specimens from patients with P. aeruginosa pneumonia. These SCVs exhibited small colonies, grayish-white color, and reduced hemolysis. More than half of the SCVs were methicillin-resistant S. aureus (MRSA), with the predominant genotype being ST1 (19.6%, 9/46). The positive rates of immune evasion-related genes (78.3% vs 53.5%) and the proportion of strong biofilm formation (65.2% vs 39.1%) were significantly higher in SCVs than in normal phenotype S. aureus. In addition, SCVs showed greater resistance to host serum and resulted in higher bacterial loads, inflammatory cytokine levels, and pathological damage in the lungs of mice at the late stage (day 28) compared to normal phenotype strains. Notably, patients with SCVs were more frequently treated with fluoroquinolones and mechanical ventilation and had longer hospital stays than those with normal phenotype strains.

S. aureus SCVs (often undetected) show a high prevalence of immune evasion genes and a strong ability to form biofilms, and may be associated with persistent pulmonary infection in patients.