Study of lug Operon, SCC mec Elements, Antimicrobial Resistance, MGEs, and STs of Staphylococcus lugdunensis Clinical Isolates Through Whole-Genome Sequencing

Abstract

Staphylococcus lugdunensis is a coagulase-negative staphylococcus known for its significant pathogenic potential, often causing severe infections such as endocarditis and bacteremia, with virulence comparable to S. aureus. Despite general susceptibility to most antibiotics, the emergence of oxacillin-resistant strains is increasingly concerning. This study conducted whole-genome sequencing on 20 S. lugdunensis isolates from Chang Gung Memorial Hospital to explore their genetic diversity, antimicrobial resistance mechanisms, and mobile genetic elements. The lugdunin biosynthetic operon, essential for antimicrobial peptide production, was present in multilocus sequence typing (MLST) types 1, 3, and 6 but absent in STs 4, 27, and 29. Additionally, IS256 insertion elements, ranging from 7 to 17 copies, were identified in four strains and linked to multidrug resistance. CRISPR-Cas systems varied across STs, with type III-A predominant in ST1 and ST6 and type IIC in ST4, ST27, and ST29; notably, ST3 lacked CRISPR systems, correlating with a higher diversity of SCCmec elements and an increased potential for horizontal gene transfer. Phage analysis revealed stable phage-host associations in ST1, ST6, and ST29, whereas ST4 displayed a varied prophage profile. Phenotypic resistance profiles generally aligned with genomic predictions, although discrepancies were observed for aminoglycosides and clindamycin. These findings highlight the complex genetic landscape and evolutionary dynamics of S. lugdunensis, emphasizing the need for genomic surveillance to inform clinical management and prevent the spread of resistant strains.

Keywords: IS256; MLST; SCCmec; Staphylococcus lugdunensis; lugdunin.

Figure 1

Structural organization of the lugdunin cassette between the rpsL and cobB genes. This figure shows the structural variation in the lugdunin (Lug) cassette located between the rpsI (left) and cobB (right) genes (green) across 20 strains. Eleven strains (SL36, SL118, SL249, SL131, SL138, SL220, SL99, SL135, SL47, SL71, and SL53) possess the full Lug cassette, while nine strains (SL195, SL29, SL35, SL37, SL167, SL248, SL30, SL149, and SL210) contain only the lugM gene (blue). An IS256 insertion (yellow) is observed in strain SL36, which interrupts the lugF gene. Genes encoding non-ribosomal peptide synthetase (NRPS) components (lugA–E) are colored red, and genes encoding the ABC transporter system (lugF–H) are colored pink.

Figure 2

IS256 copy numbers and specific insertion locations in four strains genome. (a) This figure illustrates the copy numbers of IS256 elements and the specific locations of these insertions in four strains: SL36, SL118, SL195, and SL220. Strain SL36 contains 17 copies of IS256. SL118 has 14 copies. SL195 contains 15 copies, and SL220 harbors 7 copies. For the remaining strains, no IS256 elements were detected. (b) This figure shows the structural organization of the SCCmec type II cassette (39.0 kbp) in S. lugdunensis strains SL118 and SL36. In strain SL118, two IS256 elements are present: one located near the mecI gene and the other adjacent to the IS431 element. In contrast, strain SL36 contains a single IS256 insertion located close to the mecI gene.