Staphylococcus lugdunensis: An Overview of an Atypical Coagulase-Negative Pathogen
Staphylococcus lugdunensis is a species of Gram-positive bacteria that belongs to the group of coagulase-negative staphylococci (CoNS). For decades, most CoNS species, such as *S. epidermidis*, were considered relatively low-virulence pathogens primarily causing opportunistic infections in immunocompromised patients or those with implanted medical devices. *S. lugdunensis*, however, stands out from its counterparts. Since its first identification in the late 1980s in Lyon, France (Lugdunum being the city’s Latin name), this organism has been recognized as an atypically virulent pathogen. Its clinical profile and severity of infection often resemble those caused by the much more dangerous *Staphylococcus aureus*, leading to its description as a “wolf in sheep’s clothing” or an “emerging high-virulent pathogen” that necessitates specialized clinical attention and laboratory identification protocols.
Microbiology and General Characteristics
*S. lugdunensis* is a Gram-positive, non-motile, non-spore-forming coccus that typically occurs singly, in pairs, or in irregular grapelike clusters, with an average diameter of 0.8–1.0 μm. It is a facultative anaerobe. The key microbiological feature distinguishing *S. lugdunensis* from *S. aureus* is the absence of secreted coagulase, which is why it is classified as a CoNS. However, some isolates possess a membrane-bound form of the enzyme, which has historically resulted in its misidentification as *S. aureus* in clinical laboratories using certain agglutination tests. Like other staphylococci, it is catalase-positive and oxidase-negative.
In terms of culture characteristics, *S. lugdunensis* often exhibits unique phenotypic markers that aid in its distinction from other CoNS. On Columbia agar with 5% sheep blood, *S. lugdunensis* colonies frequently display prominent beta-hemolysis after 48 hours of incubation, a trait it shares with *S. aureus* but not with most other CoNS. Furthermore, cultures of *S. lugdunensis* can emit a characteristic *Eikenella corrodens*-like odor, which, when combined with colony pleomorphism and beta-hemolysis, can significantly increase the detection rate of the organism in clinical settings. The organism can tolerate high salt concentrations (e.g., 10% NaCl) but is a non-fermenter of mannitol.
Habitat, Colonization, and Spectrum of Infection
*S. lugdunensis* is a constituent of the normal human skin flora, but its colonization is not evenly distributed across the body. It preferentially colonizes areas with higher humidity and thinner skin layers, and it is most commonly associated with the lower parts of the body and the extremities. Primary sites of carriage are the perineal, inguinal (groin), and pelvic girdle regions, as well as the nail bed of the first toe. Estimates suggest physiological colonization in 30% to 50% of the population, with a lower frequency found in the nasal cavity or nares compared to other body sites.
Despite being a common commensal, *S. lugdunensis* is an opportunistic pathogen responsible for a wide spectrum of infections. The most frequent type of infection it causes is **Skin and Soft Tissue Infections (SSTI)**, which dominate cases found in general practice. These typically manifest as abscesses, cellulitis, wound infections, and paronychias, with a high proportion of these infections occurring below the waist. SSTIs caused by *S. lugdunensis* are often invasive and may require surgical intervention in addition to antibiotic therapy.
Crucially, *S. lugdunensis* is notorious for causing **Infective Endocarditis (IE)**, particularly an acute and highly destructive form involving the native heart valves, rather than the prosthetic valve endocarditis more typical of other CoNS. Although it accounts for a small percentage of IE cases (around 1%), these infections are fulminant, frequently require urgent cardiac surgery, and are associated with a significant mortality rate, sometimes reported as high as 40%. Other invasive infections include bloodstream infections (bacteremia/sepsis), bone and joint infections, prosthetic joint infections (PJI), urinary tract infections, and infections of vascular catheters and other implanted medical devices.
Pathogenic Mechanisms and Virulence Factors
The heightened virulence of *S. lugdunensis* compared to other CoNS is attributed to a unique set of virulence factors, some of which are analogous to those found in *S. aureus*. The organism encodes an array of factors for adhesion and cytotoxicity. One key mechanism is the **Iron-Regulated Surface Determinant (Isd) system**, which, combined with a novel energy-coupling factor (ECF) mechanism, allows the bacterium to efficiently extract and utilize iron/heme from host hemoproteins, a process essential for survival and proliferation during infection.
Furthermore, *S. lugdunensis* produces **Small *S. lugdunensis* Synergistic Hemolysins (SLUSH)**, which are cytolytic peptides structurally related to the phenol-soluble modulins of *S. aureus*. These peptides can act synergistically with beta-toxin to effectively lyse erythrocytes, contributing to its prominent beta-hemolysis phenotype on blood agar and likely playing a role in tissue damage during infection. A unique virulence feature is the production of **lugdunin**, a novel peptide antibiotic. Lugdunin acts against other bacteria, including *S. aureus*, and may influence the microbial community balance on the skin and mucosal surfaces, potentially giving *S. lugdunensis* a competitive advantage in its colonization niche, though its role during invasive infection is still under investigation. The organism also demonstrates the capacity to form biofilms, an important virulence factor, particularly in device-related infections. Unlike *S. aureus*, which actively grows and often causes membrane damage in macrophages, *S. lugdunensis* has been shown to survive silently within the mature phagolysosomes of macrophages, only being released following host cell apoptosis, suggesting a fundamentally different mechanism for survival in the infected host.
Antimicrobial Susceptibility and Clinical Management
A notable and highly favorable characteristic of *S. lugdunensis* is its generally high susceptibility to a wide gamut of antibacterial therapies, which is atypical for CoNS species. Coagulase-negative staphylococci are often associated with high rates of methicillin resistance; however, *S. lugdunensis* isolates remain susceptible to many antimicrobial agents. Infections can usually be treated successfully with antibiotics traditionally used for methicillin-susceptible *S. aureus* (MSSA), such as oxacillin or cephalexin. The strict barriers to horizontal gene transfer, including the presence of CRISPR/Cas loci and toxin/antitoxin systems in its genome, are hypothesized to contribute to this slow development of antibiotic resistance. Given the potential for aggressive disease, especially infective endocarditis, prompt and accurate microbiological identification of *S. lugdunensis* is critical to ensure appropriate and effective antibiotic treatment is initiated quickly, minimizing the risk of severe clinical outcomes.