Lytic phages target biofilm-forming Staphylococcus lugdunensis in chronic rhinosinusitis
Staphylococcus lugdunensis, a coagulase-negative staphylococci (CoNS), was traditionally regarded as a harmless human commensal. However, increasing evidence demonstrates that it is an important opportunistic pathogen capable of causing skin and soft tissue infections, infective endocarditis, osteomyelitis, device-associated infections and is also associated with chronic rhinosinusitis (CRS). Unlike most CoNS, S. lugdunensis possesses numerous virulence determinants shared with S. aureus, contributing to its moderate-to-high pathogenic potential. Although it has a relatively closed pangenome and limited horizontal acquisition of virulence genes, its pathogenicity is largely attributed to intrinsic virulence factors, biofilm-forming ability, and coexistence with other staphylococci, particularly S. aureus. Until recently, S. lugdunensis remained susceptible to most clinically relevant antibiotics. However, the emergence of methicillin-resistant S. lugdunensis (MRSL) since 2003 has raised clinical concern. Biofilm formation is a major contributor to the persistence and pathogenicity of S. lugdunensis, although its molecular mechanisms remain incompletely understood. While all sequenced strains possess the ica locus responsible for PNAG (poly-beta-1,6-N-acetyl-D-glucosamine) synthesis, experimental studies suggest that mature biofilms are predominantly proteinaceous rather than polysaccharide-based. Recent analyses have shown that extracellular proteins, polysaccharides, and extracellular DNA can all contribute to the biofilm matrix, although proteins often represent a major structural component .Bacteriophages (phages) are viruses that specifically infect bacteria and are increasingly recognised as promising alternatives or adjuncts to antibiotics due to their high host specificity and bactericidal activity. Among staphylococci, phages infecting S. aureus have been extensively investigated, with well-established applications in phage therapy. In contrast, only a limited number of S. lugdunensis-associated phages have been reported. These include the prophage-derived integrase system phiSL01, which has been utilised as a site-specific chromosomal integration tool, and the recently described lytic phage APTC-SL.1 which exhibits lytic activity against clinical S. lugdunensis isolates. Furthermore, several phages originally isolated from other staphylococcal species have demonstrated infectivity against selected S. lugdunensis strains during large-scale host-range studies. Nevertheless, the diversity, biology, host range, and genomic characteristics of S. lugdunensis phages remain largely unexplored, representing a significant gap compared with the extensive knowledge available for S. aureus and S. epidermidis phages. Expanding the repertoire of S. lugdunensis phages is important for both fundamental and translational research. Their ability to replicate at infection sites, lyse biofilm-associated bacteria, and in some cases biofilm matrix-degrading enzymes makes them particularly attractive for treatments where conventional antibiotics often fail.