Search Results (32)

Despite the critical role of lipid-mediated signaling in regulating host immunity, endorsed by growing evidence, the interaction between lipid metabolism and immune response remains largely unknown. This review aims to elucidate the immunomodulatory role of a lung-enriched lipid metabolic pathway mediated by the phospholipase A2 (PLA₂) family, which comprises a diverse range of lipid-hydrolyzing enzymes. Based on their location, structure, substrate specificity and physiological roles, PLA₂s can be classified into secreted PLA₂s (sPLA₂s), cytosolic PLA₂s (cPLA₂s), calcium-independent PLA₂s (iPLA₂s), and lysosomal-associated PLA₂s (lPLA₂s). These PLA₂ isoforms are similar in that they can all cleave cellular membrane-associated phospholipids, releasing free lysophospholipids and fatty acids such as arachidonic acid, which subsequently serve as precursors for a wide range of bioactive mediators responsible for physiological functions and pathological changes. Respiratory infections, especially those caused by bacteria and viruses, represent a substantial threat to the health of the population worldwide and cause billions of disease cases and millions of deaths annually. Respiratory infections provoke airway inflammation, characterized by increased vascular permeability and the influx of immune cells, resulting in tissue damage, impaired gas exchange, acute respiratory distress syndrome (ARDS) and even death. During infections and inflammatory milieu, airway-expressed PLA₂ can further increase and exhibit protection by restricting pathogens and inflammation or, in contrast, exacerbate the pathogenesis. In this manuscript, we will provide an overview of the current knowledge on the biological functions of PLA₂ isoforms, especially concerning membrane-associated isoforms in respiratory infections, and offer insight into the spatial and temporal regulation of immune responses mediated by PLA₂ and the subsequent modulation of host–pathogen interactions and the balance between protective effects and pathological outcomes. Full article

Despite the ethnobotanical significance of Chilean Colliguaja species, research on their biological activities and phytochemical composition remains limited. Among these species, Colliguaja odorifera Molina (Euphorbiaceae), traditionally used in folk medicine to alleviate toothaches, stands out for its potential for medicinal applications. This study aims to investigate the anti-inflammatory activity of the C. odorifera leaf extracts and their secondary metabolites isolated from the most active extract. A hydroalcoholic extract of C. odorifera leaves was prepared, and subsequently ethyl acetate (EA-E), n-butanol (B-E), and water (W-E) extracts were obtained by liquid–liquid partition. The extracts were first evaluated for their ability to inhibit lipoxygenase, and the most active extract was subsequently tested for hyaluronidase (HA) and secretory phospholipase A2 (sPLA₂). The most active extract was EA-E, with IC₅₀ values of 11.75, 31.09, and 6.60 µg/mL for anti-LOX activity, hyaluronidase, and sPLA₂, respectively. This extract was analyzed by chromatography coupled to mass spectrometry and ¹H and ¹³C NMR spectroscopy, allowing the identification, for the first time, of shikimic acid, gallic acid, methyl gallate, ethyl gallate, and a putative galloyl-luteolin. These results suggest that C. odorifera is a promising candidate for the development of natural alternatives to nonsteroidal anti-inflammatory drugs. Full article

Background: Physical activity (PA) provides significant health benefits, yet inactivity remains high in Spain, especially among adolescents and increasingly in children. Identifying barriers to PA is essential, but available tools are mainly designed for adolescents. This study aimed to adapt the “Brief Scale of Perceived Barriers to Physical Activity” for Spanish schoolchildren aged 6–12 and examine its validity and reliability. Methods: The “Brief Scale of Perceived Barriers to Physical Activity for Children” was linguistically and culturally adapted. Comprehension was assessed through cognitive interviews, and reliability was examined via a test–retest procedure with 137 Spanish schoolchildren. Several analyses were conducted, including confirmatory factor analysis (CFA) to assess the factor structure, along with reliability metrics: Cronbach’s alpha (α) for internal consistency and the intraclass correlation coefficient (ICC) for test–retest reliability. Results: CFA confirmed a four-factor structure (self-concept, motivation–interest, social support, and task incompatibility) in a sample of 137 with excellent fit indices (χ²/df = 1.394, RMSEA = 0.054, CFI = 0.976, TLI = 0.966). Internal consistency ranged from good to excellent (α = 0.831–0.979). Temporal stability was substantial to near perfect (ICC = 0.708–0.979). Measurement error was low for all items and the total score (SEM% = 6.1–37.2; MDC% = 17.0–103.0), demonstrating accuracy. Conclusions: The “Brief Scale of Perceived Barriers to Physical Activity for Children” was proven to be a reliable and valid tool for assessing perceived barriers to PA in Spanish children. It offers developmentally appropriate insights that can guide strategies to enhance supportive environments and promote long-term active behaviours. As part of the social domain, it contributes to the Spanish Physical Literacy Assessment for Children (SPLA-C) model, the first physical literacy (PL) assessment instrument developed in Spain. Full article

Background/Objectives: In Spain, a high proportion of children do not meet the recommended daily levels of physical activity (PA), which highlights the urgent need to understand the motivational factors that could influence PA behavior. Self-Determination Theory is a widely used approach for assessing motivation toward exercise, employing instruments such as the Behavioral Regulation in Exercise Questionnaire (BREQ-3). However, despite the cognitive and linguistic differences that limit its direct application, this tool has not yet been adapted for children aged 6–12 years. This study aimed to adapt the BREQ-3 for use with Spanish schoolchildren and to evaluate its validity and reliability in this age group. Methods: The BREQ-3 for children (BREQ-3C) was linguistically and culturally adapted. Comprehension was tested through cognitive interviews, and reliability was assessed via a test–retest with 125 Spanish schoolchildren. Statistical analyses: Confirmatory factor analysis (CFA), Cronbach’s alpha, and the intraclass correlation coefficient (ICC) were used to evaluate validity and reliability. Results: CFA supported the factorial structure of the adapted BREQ-3 for primary schoolchildren, showing acceptable model fit indices (chi-square minimum discrepancy/degrees of freedom (CMIN/df) = 1.552, root mean square error of approximation (RMSEA) = 0.053, comparative fit index (CFI) = 0.891, Tucker-Lewis index (TLI) = 0.870). Internal consistency ranged from poor to excellent for all items and the total score of the questionnaire (Cronbach’s alpha (α): 0.535 to 0.911), except for items 3, 13, 20, and 21, where the internal consistency was unacceptable. Test–retest reliability was generally satisfactory, with ICC values indicating fair to excellent temporal stability (ICC: 0.248 to 0.911). The measurement error indicators (standard error of measurement percentage (SEM%) and minimal detectable change percentage (MDC%)) varied widely, particularly for the less reliable items. Most item scores were not significantly different between the test and retest groups, although items 2, 3, 5, 9, 17, 19, and 20 were significantly different. Conclusions: The BREQ-3C has promising psychometric properties for assessing exercise motivation in children aged 6–12 years. This tool shows potential for use in research, education, and health interventions to understand and promote physical activity motivation in primary schools. Full article

This study aims to elucidate the synergistic antibacterial mechanism of benzyl isothiocyanate (BITC) and resveratrol (RES) on Staphylococcus aureus (S. aureus) at the transcriptional level. Compared with the individuals, the combination of BITC and RES (BITC_RES) reduced S. aureus growth, inhibited biofilm formation, and increased cell membrane disruption. The transcriptomic results showed that the BITC_RES group presented 245 and 1150 more DEGs than the BITC group and the RES group, respectively. In addition, some other key genes in the BITC_RES group, including serine protease (splA, splE), Sae regulatory system (saeR, saeS, tsaE, sau300), accessory gene regulator protein C (agrC), cysteine protease (sspB), glutamyl endopeptidase (sspA), and hemolysin toxin family-related genes (hly, lukDv, lukEv), and the relative expression of these 12 genes was downregulated by 2.2–259.8-fold, 0.8–259.8-fold and 1.2–158.2-fold greater than those in the BITC group and the RES group, respectively. Finally, a synergistic antimicrobial effect of this combination was also observed in fresh lean beef at 4 °C and 25 °C. These findings provide information for future studies on the synergistic antimicrobial effects of BITC and RES on S. aureus. Full article

Staphylococcus aureus (S. aureus) colonizes the nasal cavities of both healthy individuals and patients with chronic rhinosinusitis (CRS) with (CRSwNP) and without (CRSsNP) nasal polyps. Treatment-resistant S. aureus biofilms and intracellular persistence are common in CRS patients, requiring the expression of specific virulence factor genes to transition into these forms. We hypothesized that S. aureus isolates from non-diseased controls, CRSsNP patients, and CRSwNP patients would exhibit distinct virulence factor patterns contributing to persistence and intracellular survival in CRS patients. Nasal swabs from seventy-seven individuals yielded S. aureus cultures in eight non-diseased controls, eight CRSsNP patients, and five CRSwNP patients. Whole-genome sequencing analyzed stress, antimicrobial resistance, and virulence genes, including plasmids and prophages. Four virulence factor gene patterns emerged: a core set (hlgA, icaC, hlgB, hlgC, hld, and aur) present in all isolates, and accessory sets, including the enterotoxin gene cluster (seo, sem, seu, sei, and sen) and a partial/complete invasive virulence factor set (splE, splA, splB, lukE, and lukD) (p = 0.001). CRSwNP isolates exhibited incomplete carriage of the core set, with frequent loss of scn, icaC, and hlgA (p < 0.05). These findings suggest that S. aureus has clusters of virulence factors that may act in concert to support the survival and persistence of the bacteria, resulting in enhanced pathogenicity. This may manifest clinically with resistant disease and refractoriness to antibiotics. Full article

Cryptosporidium, a protozoan parasite affecting the gastrointestinal system, is primarily known for causing diarrhea, especially in those with weakened immune systems. However, there is increasingly persuasive evidence that it may be directly involved in tumorigenesis. This review examines some of the potential mechanisms through which Cryptosporidium infections can induce cancer, specifically chronic inflammation, manipulation of the immune system, and alteration of cell signaling pathways. Persistent inflammation with immune system changes due to chronic infection, particularly among immunocompromised hosts, leads to a microenvironment that facilitates tumorigenesis. Cryptosporidium manipulates important cellular pathways such as PI3K, NF-κB, Wnt, and p38/MAPK to promote cell survival, regulate immune responses, and foster tissue remodeling, all of which contribute to a tumor-friendly microenvironment. Moreover, Cryptosporidium virulence factors such as ROP1, sPLA2, and microRNAs disrupt host cellular stability and significantly alter host cellular gene expression, which also exacerbates inflammation and tissue damage. Epidemiological data have indicated higher rates of Cryptosporidium infection in cancer patients, especially patients with gastrointestinal cancers. This, among other observations, raises the possibility that the infection may be connected to cancer progression. In animal models, especially studies with C. parvum-challenged rodents, chronic inflammation, immune repression, and genetic mutations related to neoplasia have been reported. While this has provided us with valuable information, we still have a long way to go to fully understand the long-term ramifications of Cryptosporidium infection. These cover aspects such as the contribution of latent infections and the genetic diversity of Cryptosporidium strains in cancer. Further investigation is urgently needed to understand the molecular processes by which Cryptosporidium might contribute to carcinogenesis and explore potential strategies for therapy and prevention especially among immunocompromised populations. Full article

Integrins were originally identified as receptors for extracellular matrix (ECM) and cell-surface molecules (e.g., VCAM-1 and ICAM-1). Later, we discovered that many soluble growth factors/cytokines bind to integrins and play a critical role in growth factor/cytokine signaling (growth factor–integrin crosstalk). We performed a virtual screening of protein data bank (PDB) using docking simulations with the integrin headpiece as a target. We showed that several growth factors (e.g., FGF1 and IGF1) induce a integrin-growth factor-cognate receptor ternary complex on the surface. Growth factor/cytokine mutants defective in integrin binding were defective in signaling functions and act as antagonists of growth factor signaling. Unexpectedly, several growth factor/cytokines activated integrins by binding to the allosteric site (site 2) in the integrin headpiece, which is distinct from the classical ligand (RGD)-binding site (site 1). Since 25-hydroxycholesterol, a major inflammatory mediator, binds to site 2, activates integrins, and induces inflammatory signaling (e.g., IL-6 and TNFα secretion), it has been proposed that site 2 is involved in inflammatory signaling. We showed that several inflammatory factors (CX3CL1, CXCL12, CCL5, sPLA2-IIA, and P-selectin) bind to site 2 and activate integrins. We propose that site 2 is involved in the pro-inflammatory action of these proteins and a potential therapeutic target. It has been well-established that platelet integrin αIIbβ3 is activated by signals from the inside of platelets induced by platelet agonists (inside-out signaling). In addition to the canonical inside-out signaling, we showed that αIIbβ3 can be allosterically activated by inflammatory cytokines/chemokines that are stored in platelet granules (e.g., CCL5, CXCL12) in the absence of inside-out signaling (e.g., soluble integrins in cell-free conditions). Thus, the allosteric activation may be involved in αIIbβ3 activation, platelet aggregation, and thrombosis. Inhibitory chemokine PF4 (CXCL4) binds to site 2 but did not activate integrins, Unexpectedly, we found that PF4/anti-PF4 complex was able to activate integrins, indicating that the anti-PF4 antibody changed the phenotype of PF4 from inhibitory to inflammatory. Since autoantibodies to PF4 are detected in vaccine-induced thrombocytopenic thrombosis (VIPP) and autoimmune diseases (e.g., SLE, and rheumatoid arthritis), we propose that this phenomenon is related to the pathogenesis of these diseases. P-selectin is known to bind exclusively to glycans (e.g., sLex) and involved in cell–cell interaction by binding to PSGL-1 (CD62P glycoprotein ligand-1). Unexpectedly, through docking simulation, we discovered that the P-selectin C-type lectin domain functions as an integrin ligand. It is interesting that no one has studied whether P-selectin binds to integrins in the last few decades. The integrin-binding site and glycan-binding site were close but distinct. Also, P-selectin lectin domain bound to site 2 and allosterically activated integrins. Full article

The current work was conducted to synthesize several novel anti-inflammatory quinazolines having sulfamerazine moieties as new 3CLpro, cPLA2, and sPLA2 inhibitors. The thioureido derivative 3 was formed when compound 2 was treated with sulfamerazine. Also, compound 3 was reacted with NH₂-NH₂ in ethanol to produce the N-aminoquinazoline derivative. Additionally, derivative 4 was reacted with 4-hydroxy-3-methoxybenzaldehyde, ethyl chloroacetate, and/or diethyl oxalate to produce quinazoline derivatives 5, 6, and 12, respectively. The results of the pharmacological study indicated that the synthesized 4–6 and 12 derivatives showed good 3CLpro, cPLA2, and sPLA2 inhibitory activity. The IC₅₀ values of the target compounds 4–6, and 12 against the SARS-CoV-2 main protease were 2.012, 3.68, 1.18, and 5.47 µM, respectively, whereas those of baicalein and ivermectin were 1.72 and 42.39 µM, respectively. The IC₅₀ values of the target compounds 4–6, and 12 against sPLA2 were 2.84, 2.73, 1.016, and 4.45 µM, respectively, whereas those of baicalein and ivermectin were 0.89 and 109.6 µM, respectively. The IC₅₀ values of the target compounds 4–6, and 12 against cPLA2 were 1.44, 2.08, 0.5, and 2.39 µM, respectively, whereas those of baicalein and ivermectin were 3.88 and 138.0 µM, respectively. Also, incubation of lung cells with LPS plus derivatives 4–6, and 12 caused a significant decrease in levels of sPLA2, cPLA2, IL-8, TNF-α, and NO. The inhibitory activity of the synthesized compounds was more pronounced compared to baicalein and ivermectin. In contrast to ivermectin and baicalein, bioinformatics investigations were carried out to establish the possible binding interactions between the newly synthesized compounds 2–6 and 12 and the active site of 3CLpro. Docking simulations were utilized to identify the binding affinity and binding mode of compounds 2–6 and 12 with the active sites of 3CLpro, sPLA2, and cPLA2 enzymes. Our findings demonstrated that all compounds had outstanding binding affinities, especially with the key amino acids of the target enzymes. These findings imply that compound 6 is a potential lead for the development of more effective SARS-CoV-2 Mpro inhibitors and anti-COVID-19 quinazoline derivative-based drugs. Compound 6 was shown to have more antiviral activity than baicalein and against 3CLpro. Furthermore, the IC₅₀ value of ivermectin against the SARS-CoV-2 main protease was revealed to be 42.39 µM, indicating that it has low effectiveness. Full article

Coronavirus disease (COVID-19) has become a global pandemic. COVID-19 patients need immediate diagnosis and rehabilitation, which makes it urgent to identify new protein markers for a prognosis of the severity and outcome of the disease. The aim of this study was to analyze the levels of interleukin-6 (IL-6) and secretory phospholipase (sPLA2) in the blood of patients regarding the severity and outcome of COVID-19 infection. The study included clinical and biochemical data obtained from 158 patients with COVID-19 treated at St. Petersburg City Hospital No. 40. A detailed clinical blood test was performed on all patients, as well as an assessment of IL-6, sPLA2, aspartate aminotransferase (AST), total protein, albumin, lactate dehydrogenase (LDH), APTT, fibrinogen, procalcitonin, D-dimer, C-reactive protein (CRB), ferritin, and glomerular filtration rate (GFR) levels. It was found that the levels of PLA2, IL-6, APTV, AST, CRP, LDH, IL-6, D-dimer, and ferritin, as well as the number of neutrophils, significantly increased in patients with mild to severe COVID-19 infections. The levels of IL-6 were positively correlated with APTT; the levels of AST, LDH, CRP, D-dimer, and ferritin; and the number of neutrophils. The increase in the level of sPLA2 was positively correlated with the levels of CRP, LDH, D-dimer, and ferritin, the number of neutrophils, and APTT, and negatively correlated with the levels of GFR and lymphocytes. High levels of IL-6 and PLA2 significantly increase the risk of a severe course by 13.7 and 2.24 times, and increase the risk of death from COVID-19 infection by 14.82 and 5.32 times, respectively. We have shown that the blood levels of sPLA2 and IL-6 increase in cases which eventually result in death and when patients are transferred to the ICU (as the severity of COVID-19 infection increases), showing that IL-6 and sPLA2 can be considered as early predictors of aggravation of COVID-19 infections. Full article

Glioblastoma multiforme (GBM) is one of the most aggressive gliomas. New and more effective therapeutic approaches are being sought based on studies of the various mechanisms of GBM tumorigenesis, including the synthesis and metabolism of arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA). PubMed, GEPIA, and the transcriptomics analysis carried out by Seifert et al. were used in writing this paper. In this paper, we discuss in detail the biosynthesis of this acid in GBM tumors, with a special focus on certain enzymes: fatty acid desaturase (FADS)1, FADS2, and elongation of long-chain fatty acids family member 5 (ELOVL5). We also discuss ARA metabolism, particularly its release from cell membrane phospholipids by phospholipase A₂ (cPLA₂, iPLA₂, and sPLA₂) and its processing by cyclooxygenases (COX-1 and COX-2), lipoxygenases (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2), and cytochrome P450. Next, we discuss the significance of lipid mediators synthesized from ARA in GBM cancer processes, including prostaglandins (PGE₂, PGD₂, and 15-deoxy-Δ^12,14-PGJ₂ (15d-PGJ₂)), thromboxane A₂ (TxA₂), oxo-eicosatetraenoic acids, leukotrienes (LTB₄, LTC₄, LTD₄, and LTE₄), lipoxins, and many others. These lipid mediators can increase the proliferation of GBM cancer cells, cause angiogenesis, inhibit the anti-tumor response of the immune system, and be responsible for resistance to treatment. Full article

The aim of the study was to compare the morphological features of epicardial adipose tissue (EAT) adipocyte with the circulating inflammatory biomarkers and parameters of extracellular matrix remodeling in patients with coronary artery disease (CAD). We recruited 42 patients with CAD (m/f 28/14) who were scheduled for coronary artery bypass graft surgery (CABG). EAT adipocytes were obtained by the enzymatic method from intraoperative adipose tissue samples. Concentrations of secreted and lipoprotein-associated phospholipase A2 (sPLA2 and LpPLA2), TNF-α, IL-1β, IL-6, IL-10, high-sensitive C-reactive protein (hsCRP), metalloproteinase-9 (MMP-9), MMP-2, C-terminal cross-linking telopeptide of type I collagen (CTX-I), and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in blood serum. Patients were divided into two groups: group 1—with mean EAT adipocytes’ size ≤ 87.32 μm; group 2—with mean EAT adipocytes’ size > 87.32 μm. Patients of group 2 had higher concentrations of triglycerides, hsCRP, TNF-α, and sPLA2 and a lower concentration of CTX-I. A multiple logistic regression model was created (R_N² = 0.43, p = 0.0013). Concentrations of TNF-α, sPLA2 and CTX-I appeared to be independent determinants of the EAT adipocyte hypertrophy. ROC analysis revealed the 78% accuracy, 71% sensitivity, and 85% specificity of the model, AUC = 0.82. According to our results, chronic low-grade inflammation and extracellular matrix remodeling are closely associated with the development of hypertrophy of EAT adipocytes, with serum concentrations of TNF-α, sPLA2 and CTX-I being the key predictors, describing the variability of epicardial adipocytes’ size. Full article

The phospholipase A2 (PLA2) superfamily of phospholipase enzymes hydrolyzes the ester bond at the sn-2 position of the phospholipids, generating a free fatty acid and a lysophospholipid. The PLA2s are amphiphilic in nature and work only at the water/lipid interface, acting on phospholipid assemblies rather than on isolated single phospholipids. The superfamily of PLA2 comprises at least six big families of isoenzymes, based on their structure, location, substrate specificity and physiologic roles. We are reviewing the secreted PLA2 (sPLA2), cytosolic PLA2 (cPLA2), Ca²⁺-independent PLA2 (iPLA2), lipoprotein-associated PLA2 (LpPLA2), lysosomal PLA2 (LPLA2) and adipose-tissue-specific PLA2 (AdPLA2), focusing on the differences in their structure, mechanism of action, substrate specificity, interfacial kinetics and tissue distribution. The PLA2s play important roles both physiologically and pathologically, with their expression increasing significantly in diseases such as sepsis, inflammation, different cancers, glaucoma, obesity and Alzheimer’s disease, which are also detailed in this review. Full article

Introduction: Snakebite is an urgent, unmet global medical need causing significant morbidity and mortality worldwide. Varespladib is a potent inhibitor of venom secretory phospholipase A₂ (sPLA₂) that can be administered orally via its prodrug, varespladib-methyl. Extensive preclinical data support clinical evaluation of varespladib as a treatment for snakebite envenoming (SBE). The protocol reported here was designed to evaluate varespladib-methyl for SBE from any snake species in multiple geographies. Methods and Analysis: BRAVO (Broad-spectrum Rapid Antidote: Varespladib Oral for snakebite) is a multicenter, randomized, double-blind, placebo-controlled, phase 2 study to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl plus standard of care (SoC) vs. SoC plus placebo in patients presenting with acute SBE by any venomous snake species. Male and female patients 5 years of age and older who meet eligibility criteria will be randomly assigned 1:1 to varespladib-methyl or placebo. The primary outcome is the Snakebite Severity Score (SSS) that has been modified for international use. This composite outcome is based on the sum of the pulmonary, cardiovascular, nervous, hematologic, and renal systems components of the updated SSS. Ethics and Dissemination: This protocol was submitted to regulatory authorities in India and the US. A Clinical Trial No Objection Certificate from the India Central Drugs Standard Control Organisation, Drug Controller General-India, and a Notice to Proceed from the US Food and Drug Administration have been obtained. The study protocol was approved by properly constituted, valid institutional review boards or ethics committees at each study site. This study is being conducted in compliance with the April 1996 ICH Guidance for Industry GCP E6, the Integrated Addendum to ICH E6 (R2) of November 2016, and the applicable regulations of the country in which the study is conducted. The trial is registered on Clinical trials.gov, NCT#04996264 and Clinical Trials Registry-India, 2021/07/045079 000062. Full article

Staphylococcus aureus is a major cause of ocular infectious (corneal infection or microbial keratitis (MK) and conjunctivitis) and non-infectious corneal infiltrative events (niCIE). Despite the significant morbidity associated with these conditions, there is very little data about specific virulence factors associated with the pathogenicity of ocular isolates. A set of 25 S. aureus infectious and niCIEs strains isolated from USA and Australia were selected for whole genome sequencing. Sequence types and clonal complexes of S. aureus strains were identified by using multi-locus sequence type (MLST). The presence or absence of 128 virulence genes was determined by using the virulence finder database (VFDB). Differences between infectious (MK + conjunctivitis) and niCIE isolates from USA and Australia for possession of virulence genes were assessed using the chi-square test. The most common sequence types found among ocular isolates were ST5, ST8 while the clonal complexes were CC30 and CC1. Virulence genes involved in adhesion (ebh, clfA, clfB, cna, sdrD, sdrE), immune evasion (chp, esaD, esaE, esxB, esxC, esxD), and serine protease enzymes (splA, splD, splE, splF) were more commonly observed in infectious strains (MK + conjunctivitis) than niCIE strains (p = 0.004). Toxin genes were present in half of infectious (49%, 25/51) and niCIE (51%, 26/51) strains. USA infectious isolates were significantly more likely to possess splC, yent1, set9, set11, set36, set38, set40, lukF-PV, and lukS-PV (p < 0.05) than Australian infectious isolates. MK USA strains were more likely to possesses yent1, set9, set11 than USA conjunctivitis strains (p = 0.04). Conversely USA conjunctivitis strains were more likely to possess set36 set38, set40, lukF-PV, lukS-PV (p = 0.03) than MK USA strains. The ocular strain set was then compared to 10 fully sequenced non-ocular S. aureus strains to identify differences between ocular and non-ocular isolates. Ocular isolates were significantly more likely to possess cna (p = 0.03), icaR (p = 0.01), sea (p = 0.001), set16 (p = 0.01), and set19 (p = 0.03). In contrast non-ocular isolates were more likely to possess icaD (p = 0.007), lukF-PV, lukS-PV (p = 0.01), selq (p = 0.01), set30 (p = 0.01), set32 (p = 0.02), and set36 (p = 0.02). The clones ST5, ST8, CC30, and CC1 among ocular isolates generally reflect circulating non-ocular pathogenic S. aureus strains. The higher rates of genes in infectious and ocular isolates suggest a potential role of these virulence factors in ocular diseases. Full article