The pathogenicity of the opportunistic human fungal pathogen Candida albicans depends on its ability to escape destruction by the host immune system. Using mutant strains that are defective in cell surface glycosylation, cell wall protein synthesis, and yeast-hypha morphogenesis, we have investigated three important aspects of C. albicans innate immune interactions: phagocytosis by primary macrophages and macrophage cell lines, hyphal formation within macrophage phagosomes, and the ability to escape from and kill macrophages. We show that cell wall glycosylation is critically important for the recognition and ingestion of C. albicans by macrophages. Phagocytosis was significantly reduced for mutants deficient in phosphomannan biosynthesis (mmn4⌬, pmr1⌬, and mnt3 mnt5⌬), whereas O-and N-linked mannan defects (mnt1⌬ mnt2⌬ and mns1⌬) were associated with increased ingestion, compared to the parent wild-type strains and genetically complemented controls. In contrast, macrophage uptake of mutants deficient in cell wall proteins such as adhesins (ece1⌬, hwp1⌬, and als3⌬) and yeast-locked mutants (clb2⌬, hgc1⌬, cph1⌬, efg1⌬, and efg1⌬ cph1⌬), was similar to that observed for wild-type C. albicans. Killing of macrophages was abrogated in hypha-deficient strains, significantly reduced in all glycosylation mutants, and comparable to wild type in cell wall protein mutants. The diminished ability of glycosylation mutants to kill macrophages was not a consequence of impaired hyphal formation within macrophage phagosomes. Therefore, cell wall composition and the ability to undergo yeast-hypha morphogenesis are critical determinants of the macrophage's ability to ingest and process C. albicans.
Bronchiectasis is a heterogeneous, chronic condition with many aetiologies. It poses a significant burden on patients and healthcare practitioners and services. Clinical exacerbations often result in reduced quality of life, increased rate of lung function decline, increased hospitalisation, and mortality. Recent focus in respiratory research, guidelines, and future management options has improved this clinical field in evidence-based practice, but further work and phase III clinical trials are required. This article aims to summarise and explore advances in management strategies in recent years and highlight areas of research and future focus.
Esophageal malignancy is a disease with poor prognosis. Curative therapy incorporates surgery and is burdensome with high rates of infection morbidity and mortality. The role of yeast as causative organisms of post-esophagectomy infections is poorly defined. Consequently, the benefits of specific antifungal prophylactic therapy in improving patient outcome are unclear. Therefore, this study aimed at investigating the incidence of yeast infections at the University Medical Center Groningen among 565 post-esophagectomy patients between 1991 and 2017. The results show that 7.3% of the patients developed a yeast infection after esophageal resection with significantly increased incidence among patients suffering from diabetes mellitus. For patients with yeast infections, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, more frequent intensive care unit readmissions, prolonged hospital stays and higher mortality rates were observed. One-year survival was significantly lower for patients with a yeast infection, as well as diabetes mellitus and yeast-positive pleural effusion. We conclude that the incidence of yeast infections following esophagectomy is considerable, and that patients with diabetes mellitus are at increased risk. Furthermore, yeast infections are associated with higher complication rates and mortality. These observations encourage further prospective investigations on the possible benefits of antifungal prophylactic therapy for esophagectomy patients.Esophageal cancer is an aggressive disease associated with poor prognosis and a 5-year survival of 10% 1,2 . The curative treatment, when applicable, is neo-adjuvant chemoradiotherapy with surgical resection and radical lymphadenectomy. Although some benign disorders can result in esophagectomy, esophageal malignancy is the main reason for resection. Despite medical, surgical, nutritional and critical care advances, esophagectomy remains an operative intervention with high morbidity and mortality even when compared to other complex surgical procedures. Mortality rates vary depending on many factors and have been reported as 5-10% 3-5 . However, morbidity occurs in over 50% of cases and pulmonary complications, are almost universally seen as the greatest post-operative challenge for healthcare providers 6 . Moreover, patients who suffer from pneumonia show a seven-fold increase in mortality 7 . Causative microorganisms for pulmonary infection usually belong to the oropharyngeal flora, as this is likely the result of cervical anastomosis leakage.Risk factors for yeast infections can be split into host, pathogen and health-care associated aspects. In the former category, immune-compromising conditions, older age, malignancy, corticosteroid or cytotoxic therapy and neutropenia have all shown to increase the risk of invasive Candida infections 8 . Mechanically ventilated, critically ill patients suffer from colonization with Candida species in 25% of cases, whereas colonization occurs in 50% of the patients suspected of ventilator-associa...
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