Candida lusitaniae, a relatively uncommon yeast, has been associated with nosocomial (hospital-acquired) infections, particularly in individuals with compromised immune systems. Understanding its epidemiology is still limited, but notable data sheds light on its prevalence and impact. A study conducted in 2019 analyzed candidemia cases occurring from 2004 to 2008, revealing that Candida lusitaniae accounted for just 1.2% of the cases.

The crude 12-week mortality rate for candidemia caused by this yeast was approximately 34.8%, a figure closely aligned with the overall candidemia mortality rate of 35.2%. Another investigation spanning 1998 to 2006 at the University Children’s Hospital Münster showed that C. lusitaniae was the causative agent in 7.1% of candidemias among patients under 20 years old.  

A specific instance in 2003 marked 55 reported cases of C. lusitaniae-caused candidiasis, predominantly bloodstream infections. An intriguing aspect of this study was the prevalence of underlying medical conditions in three-quarters of the subjects, contributing to a 5% mortality rate. Further insight from a Texas cancer center’s analysis between 1988 and 1999 revealed that 75% of patients afflicted by C. lusitaniae infection were neutropenic, with a 25% mortality rate likely linked to the yeast’s notable resistance to amphotericin B.  

Instances of outbreaks have also been documented, like a neonatal intensive-care unit outbreak in 1991, where the same yeast strain infected 11 infants. This outbreak was traced back to a contaminated bottle of liquid soap, resulting in a 6.6% infection rate among exposed infants and an 18.2% mortality rate. A retrospective study encompassing 1985 to 1990, involving 98 patients with nosocomial acquisition of Candida lusitaniae, demonstrated an incidence rate of 0.3 instances per 1000 patients.

Predominantly affecting blood (54%), urine (23%), and the respiratory tract (10%), the overall mortality rate stood at 29%, with an attributable mortality rate of 14%. In general, the prevalence of this yeast among clinical Candida isolates ranges from 0.2% to 5%.  

Several risk factors for Candida lusitaniae infections have been identified, including hematologic malignancy, bone marrow transplantation, neutropenia, prior use of antifungal agents, and central venous catheters. These factors contribute to the vulnerability of certain patient populations to C. lusitaniae-related infections. 

Classification and Structure: 

Kingdom: Fungi 

Division: Ascomycota 

Class: Saccharomycetes 

Order: Saccharomycetales 

Family: Saccharomycetaceae 

Genus: Candida 

Species: Candida lusitaniae   

Candida lusitaniae exhibits a dimorphic nature, displaying both yeast and pseudohyphal forms.   

The yeast cells take on oval, ellipsoidal, or elongated shapes, measuring around 2–6 by 2–10 µm. On the other hand, the pseudohyphae consist of elongated cells with constricted budding necks dividing the compartments.   

Much like its Candida counterparts, the structure of C. lusitaniae encompasses a cell wall comprising mannosylated glycoproteins, β-glucans, and chitin alongside a cell membrane enriched with ergosterol. 

Certain strains of Candida lusitaniae exhibit unique characteristics that set them apart. For instance, strains like CBS4413 and CBS1944 are distinguished by their opposite mating types, enabling conjugation and spore formation. Conversely, ATCC38533 stands out for its resistance to the antifungal amphotericin B. Additionally, strains like Kw2611/17, isolated from patients in Kuwait, highlight geographical associations that could suggest varying virulence or resistance patterns.  

Genomic analyses have further illuminated Candida lusitaniae‘s attributes. The nuclear genome sequence of C. lusitaniae ATCC 42720 spans 12.11 mb, boasting a 44.5% GC content, 6153 protein-encoding genes, and five pseudogenes. A recent study extended this understanding, sequencing five strains, including DSY4606 (P1). This strain encompasses 12.08 mb, with a GC content of 44.53%, harboring 5676 protein-encoding genes among 5882 predicted genes, along with nine rRNA genes and 197 tRNA genes.

C. lusitaniae‘s mannan structure mirrors C. albicans, with distinct β-1,2-mannose residues within N-linked mannan side chains. Essential polysaccharides, β-1,3-glucan, and chitin, reside beneath cell wall proteins, anchored by glycosylphosphatidylinositol. These proteins are pivotal for cell wall integrity and environmental interactions.

Essential genetic elements in C. lusitaniae include E0198_001093, modulating phagocytosis, A9F13_12g01265 as a survival signaling mucin, and CLUG_01501 for thermotolerance. Adhesins like CLUG_03274 and FOB63_002933 facilitate oral mucosa adherence, underlining their colonization potential. 

Despite being a less common pathogen among Candida species, Candida lusitaniae has distinctive attributes influencing its pathogenic potential. Candida lusitaniae, like other Candida species, employs adhesins, specialized cell wall glycoproteins, to adhere to host cells.

Adhesion is a critical initial step in the infective process, allowing the fungus to attach to surfaces like epithelial cells. Although C. lusitaniae does not cause damage as other Candida species do upon colonization, it still attaches to host epithelial cells. However, compared to species like C. albicans, its lower adhesion properties contribute to its relatively lower virulence.   

Biofilms are complex microbial communities encased in a protective matrix, enabling resistance to host immune responses and antifungal treatments. While C. lusitaniae‘s ability to form biofilms has been explored, it is less effective in forming mixed biofilms with certain species like C. tropicalis. The biofilm formation process in C. lusitaniae is influenced by temperature and growth phases. 

Cell surface hydrophobicity plays a role in fungal adhesion. Interestingly, C. lusitaniae displays higher wall hydrophobicity than other species, but this doesn’t correlate directly with its adhesion properties. Phenotypic switching, a phenomenon where fungal cells switch between hydrophilic and hydrophobic phenotypes, contributes to Candida‘s ability to adapt to changing environments.

In C. lusitaniae, this phenomenon is associated with drug resistance, impacting its overall virulence. C. lusitaniae possesses a set of virulence factors, including hydrolytic enzymes like secreted aspartyl proteinases (SAPs), phospholipases, and lipases. These factors enable the fungus to penetrate host tissues and evade the immune response. However, the activity of these factors in C. lusitaniae is comparatively subdued, possibly contributing to its reduced virulence.

The initial step in mounting an immune response against Candida species involves recognizing invading fungi through pattern recognition receptors (PRRs). The overarching framework remains consistent despite variations in how different innate immune cells identify Candida. This framework centers on detecting conserved PAMPs (pathogen-associated molecular patterns) by various families of PRRs, including C-type lectin receptors, NOD-like receptors, and Toll-like receptors. Extracellular TLRs like TLR4 & TLR2 trigger the release of pro-inflammatory cytokines in response to infections.   

Intracellular TLRs such as TLR9 & TLR3 may also contribute to anti-Candida host responses. Notably, chitin from Candida albicans has found to induce interleukin-10 production via a nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-dependent mechanism, potentially attenuating pro-inflammatory host reactions during C. lusitaniae infection.   

Significant receptors, including Fc receptors for IgG (FcγRs), dectin 3, dectin 2, and dectin 1, activate responses dependent on SYK or spleen tyrosine kinase. Dectin 1’s interaction with TLR2 triggers intracellular signaling via RAF1- & SYK-dependent pathways. CR3 or Complement receptor 3 recognizes unopsonized Candida, while FcγRs facilitate opsonized Candida recognition by activated neutrophils.   

Candida hyphae’s penetration of epithelial cells involves induced endocytosis and active penetration mechanisms. Epithelial cells respond to Candida colonization from TLR4-dependent pathways, activating JUN & NF-κB. As Candida transitions to hyphae, it triggers MAPK1 and FOS signaling, enabling detection of tissue invasion. Epithelial cells also produce β-defensins responding to IL-22, controlling Candida‘s commensal state. Macrophages & monocytes serves essential roles in controlling disseminated fungal infections.  

Neutrophils employ oxidative and non-oxidative mechanisms to counter Candida, with compensatory mechanisms mitigating NADPH oxidase and MPO deficiencies in vivo. These multifaceted defense strategies ensure a robust response against Candida lusitaniae.  The NLRs, notably the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome, hold crucial roles. Candida hyphae, but not yeasts, activate the NLRP3 inflammasome, allowing the host to differentiate between colonization and invasion.

Activation of NLRP3 by Candida hyphae or secreted aspartic protease (Sap) proteins triggers caspase 1-mediated cleavage of pro-IL-18 & pro-IL-1β into active cytokines. Additionally, cleavage of pro-IL-1β by caspase 8 results in active IL-1β with response to Candida. Serine proteases derived from neutrophils convert pro-IL-1β to functional IL-1β. Candida promotes IL-1 activity by unleashing proteases that cleave pro-IL-1β. DC-SIGN, a dendritic cell-specific ICAM3-grabbing non-integrin, detects Candida‘s N-linked mannans and contributes to T helper (TH) cell responses.

While Candida-derived ligands for the C-type lectin receptors MINCLE are yet to be identified, galectin 3 binds Candida-derived -mannans. Although the importance of melanoma differentiate-associated protein 5 (MDA5) in anti-Candida host reactions is well recognized, the exact ligand that activates MDA5 remains unknown. This complex network of signaling pathways regulates the secretion of chemokines and cytokines, culminating in phagocytosis to eradicate Candida infections.   

Candida lusitaniae, a yeast species capable of causing human infections, primarily targets individuals with compromised immune systems. The infections it induces can present various clinical manifestations associated with distinct symptoms.

One common manifestation is fungemia, where the yeast enters the bloodstream, leading to fever, chills, rapid heart rate, and low blood pressure. Notably, C. lusitaniae‘s resistance to the antifungal drug amphotericin B can complicate treatment, potentially resulting in severe complications such as endocarditis, osteomyelitis, and septic shock.  

Another perilous manifestation is meningitis, a brain and spinal cord infection. This condition can evoke severe headaches, neck stiffness, confusion, sensitivity to light, and nausea. Swift intervention is imperative, as Candida lusitaniae meningitis risks fatality if left untreated. 

Additionally, this yeast can provoke localized infections in various body sites, including the respiratory tract, vagina, skin, and wounds. Symptoms vary based on the infection site: 

• Respiratory tract infections may yield coughing, shortness of breath, chest pain, and sputum production. 
• Vaginal infections might lead to itching, burning, discharge, and pain during intercourse. 
• Skin infections could result in redness, swelling, warmth, and pus formation. 
• Wound infections may exhibit delayed healing, increased drainage, and heightened inflammation. 

Culture method: Chromogenic agars like Candida ID agar and CHROMagar Candida agar offer a visual approach to identify Candida species presumptively. Candida ID agar uses an indolyl glucosaminide substrate that generates distinct colony colors upon hydrolysis by different Candida species.

While C. lusitaniae colonies appear pink, this color can also be seen in other species like C. tropicalis and C. guilliermondii. CHROMagar Candida agar, utilizing a chromogenic substrate of β-glucosaminidase, shows purple and white colonies. However, the similarity in coloration with C. krusei and C. parapsilosis raises challenges in accurate C. lusitaniae identification.   

Blood Culture for Invasive Candidiasis: Blood culture remains a primary diagnostic tool for invasive candidiasis, a severe infection affecting the bloodstream and organs. A blood sample from the patient is cultured to detect Candida growth. Although effective, this method may take several days for results and might not detect low yeast levels sensitively.   

Morphology Analysis: Corn meal agar serves as a valuable medium for 

morphological identification of Candida species, including C. lusitaniae. Under microscopic examination, C. lusitaniae displays ovoid yeast cells arranged in pairs or chains. Abundantly branched and curved pseudohyphae can also be observed. Some strains may exhibit rudimentary or absent pseudohyphae, contributing to the variability in morphological features.   

Molecular identification using Species-Specific Probes: Advancements in molecular techniques enable early and precise Candida species identification. Specific probes targeting the ITS2 region of the rRNA-encoding gene have been designed, allowing the differentiation of over 18 Candida species, including C. lusitaniae. Universal fungal primers and species-specific probes enhance the accuracy of this approach, reducing the time required for identification.   

Phenotypic Identification: It relies on the physical and biochemical characteristics of C. lusitaniae. Instruments like VITEK 2 YST, API 20C, BD Phoenix yeast identification system, MicroScan, RapID Yeast Plus, or cornmeal agar are employed. However, risks of misidentification exist, as C. lusitaniae can be confused with other Candida species or Rhodotorula glutinis. To ensure accuracy, phenotypic identification should be corroborated by molecular detection or alternative methods.  

Molecular detection techniques, such as PCR, offer rapid and precise identification of Candida lusitaniae in biological samples like blood, urine, or swabs. The absence of yeast growth or mixed Candida species does not hinder this method’s accuracy. MycoScreen™ is another option, identifying a range of yeast-like fungi, including C. lusitaniae. 

• Conduct regular surveillance cultures in high-risk healthcare settings like intensive care, neonatal, and hemodialysis units. Early detection of Candida lusitaniae colonization or infection through surveillance can guide timely interventions, proper treatment, and infection control strategies. 

• Implement rigorous infection control measures to prevent the cross-transmission of Candida lusitaniae among patients and healthcare workers. These practices include meticulous hand hygiene, appropriate use of personal protective equipment, thorough environmental cleaning and disinfection, and isolation protocols for infected or colonized patients. 

• Administer appropriate antifungal prophylaxis to individuals at high risk of Candida lusitaniae infections, such as those with hematologic malignancies, neutropenia, bone marrow transplantation, or a history of antifungal use. Fluconazole, with its in vitro activity against C. lusitaniae, is a common choice for prophylaxis and is available in both oral and intravenous forms. 

Candida Lusitaniae – an overview | ScienceDirect Topics  

Candida lusitaniae: Biology, Pathogenicity, Virulence Factors, Diagnosis, and Treatment – PMC (nih.gov)