Human Antimicrobial Peptide LL-37 Inhibits Adhesion of Candida albicans by Interacting with Yeast Cell-Wall Carbohydrates

Candida albicans is the major fungal pathogen of humans. Fungal adhesion to host cells is the first step of mucosal infiltration. Antimicrobial peptides play important roles in the initial mucosal defense against C. albicans infection. LL-37 is the only member of the human cathelicidin family of antimicrobial peptides and is commonly expressed in various tissues and cells, including epithelial cells of both the oral cavity and urogenital tract. We found that, at sufficiently low concentrations that do not kill the fungus, LL-37 was still able to reduce C. albicans infectivity by inhibiting C. albicans adhesion to plastic surfaces, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. Moreover, LL-37-treated C. albicans floating cells that did not adhere to the underlying substratum aggregated as a consequence of LL-37 bound to the cell surfaces. According to the results of a competition assay, the inhibitory effects of LL-37 on cell adhesion and aggregation were mediated by its preferential binding to mannan, the main component of the C. albicans cell wall, and partially by its ability to bind chitin or glucan, which underlie the mannan layer. Therefore, targeting of cell-wall carbohydrates by LL-37 provides a new strategy to prevent C. albicans infection, and LL-37 is a useful, new tool to screen for other C. albicans components involved in adhesion

Viral, bacterial, and fungal infections of the oral mucosa:Types, incidence, predisposing factors, diagnostic algorithms, and management

For millions of years, microbiota residing within us, including those in the oral cavity, coexisted in a harmonious symbiotic fashion that provided a quintessential foundation for human health. It is now clear that disruption of such a healthy relationship leading to microbial dysbiosis causes a wide array of infections, ranging from localized, mild, superficial infections to deep, disseminated life-threatening diseases. With recent advances in research, diagnostics, and improved surveillance we are witnessing an array of emerging and re-emerging oral infections and orofacial manifestations of systemic infections. Orofacial infections may cause significant discomfort to the patients and unnecessary economic burden. Thus, the early recognition of such infections is paramount for holistic patient management, and oral clinicians have a critical role in recognizing, diagnosing, managing, and preventing either new or old orofacial infections. This paper aims to provide an update on current understanding of well-established and emerging viral, bacterial, and fungal infections manifesting in the human oral cavity.</p

Right ventricular functional recovery assessment with stress echocardiography and cardiopulmonary exercise testing after pulmonary embolism: a pilot prospective multicentre study

Background Data on right ventricular (RV) exercise adaptation following acute intermediate and high-risk pulmonary embolism (PE) remain limited. This study aimed to evaluate the symptom burden, RV functional recovery during exercise and cardiopulmonary exercise parameters in survivors of intermediate and high-risk acute PE. Methods We prospectively recruited patients following acute intermediate and high-risk PE at four sites in Australia and UK. Study assessments included stress echocardiography, cardiopulmonary exercise testing (CPET) and ventilation–perfusion (VQ) scan at 3 months follow-up. Results Thirty patients were recruited and 24 (median age: 55 years, IQR: 22) completed follow-up. Reduced peak oxygen consumption (VO2) and workload was seen in 75.0% (n=18), with a persistent high symptom burden (mean PEmb-QoL Questionnaire 48.4±21.5 and emPHasis-10 score 22.4±8.8) reported at follow-up. All had improvement in RV-focused resting echocardiographic parameters. RV systolic dysfunction and RV to pulmonary artery (PA) uncoupling assessed by stress echocardiography was seen in 29.2% (n=7) patients and associated with increased ventilatory inefficiency (V̇E/V̇CO2 slope 47.6 vs 32.4, p=0.03), peak exercise oxygen desaturation (93.2% vs 98.4%, p=0.01) and reduced peak oxygen pulse (p=0.036) compared with controls. Five out of seven patients with RV–PA uncoupling demonstrated persistent bilateral perfusion defects on VQ scintigraphy consistent with chronic thromboembolic pulmonary vascular disease. Conclusion In our cohort, impaired RV adaptation on exercise was seen in almost one-third of patients. Combined stress echocardiography and CPET may enable more accurate phenotyping of patients with persistent symptoms following acute PE to allow timely detection of long-term complications.Full Tex