Person:

Vyas, Jatin

Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi.

Background: Dectin-1 is able to recognize and phagocytose the fungal carbohydrate, β-1,3-glucan, but its contribution to phagosomal maturation has not been explored.

Results: Dectin-1-dependent Syk activation promotes phagolysosomal fusion and acidification.

Conclusion: Dectin-1-dependent Syk-activation permits egress of early phagosomes to mature phagolysosomes.

Significance: The surface recognition receptor, Dectin-1 shapes anti-fungal responses by controlling fungal phagosome maturation.

Abstract Background: Procalcitonin (PCT) is a biomarker that is finding increasing diagnostic and prognostic utility in lower respiratory infections. It remains unclear, however, whether it can be helpful in predicting the bacterial etiology of pneumonia, with a view to informing antibiotic choice and duration. This study examines the relationship between serial PCT measurements and microbial etiology in patients hospitalized for pneumonia to determine whether changes in PCT levels provide discriminatory information on microbial etiology. Methods: We performed a subgroup analysis of data from a prospective cohort study of 505 patients admitted to a tertiary care center with findings concerning for pneumonia. Microbial etiology of pneumonia was determined from high quality respiratory samples, blood cultures or other relevant diagnostic tests according to standard protocols. Procalcitonin levels were measured serially during the first four days of hospitalization. We compared procalcitonin levels between different bacterial etiologies over the first four days of admission, using the Mann–Whitney-U test to assess for statistical significance. Results: Out of 505 patients, the diagnosis of pneumonia was adjudicated in 317, and bacterial etiology determined in 62 cases. The predominant pathogens were Staphylococcus aureus (N = 18), Streptococcus pneumoniae (N = 6), Pseudomonas aeruginosa (N = 11) and Haemophilus influenza (N = 5). Admission levels of PCT were lowest in Pseudomonas infections and highest in pneumococcal infections, though not reaching statistical significance. On hospital days two and three, pneumococcal procalcitonin levels were significantly higher than all other etiologies, but on day four, there was no statistically significant difference in PCT values for different microbial etiologies. Conclusion: Serial procalcitonin levels during the early course of bacterial pneumonia reveal a difference between pneumococcal and other bacterial etiologies, and may have an adjunct role in guiding antibiotic choice and duration. Disclosures All authors: No reported disclosures.