ABSTRACT
[This corrects the article DOI: 10.1371/journal.pntd.0010078.].
ABSTRACT
Azoles were used as the primary antifungal agents to treat the Cryptococcus gattii infection. Evidence showed that subtypes of C. gattii respond differently to azoles, but the mechanism is largely elusive. In this study, we aimed to find the mechanisms of differences in azole drug susceptibility in different subtypes of C. gattii. Eight clinical strains of C. gattii were collected for molecular typing, multilocus sequence typing (MLST) analysis, and antifungal susceptibility testing. Based on drug susceptibility differences, the RNA sequencing data were analyzed to find candidate azole drug susceptibility genes, and qPCR validation was performed. Five VGI subtypes and three VGII subtypes were identified among the eight strains of C. gattii. The clinical isolates showed high genetic diversity, and seven sequence types (STs) were identified. The geometric mean (GM) of minimum inhibitory concentration (MIC) for fluconazole, voriconazole, and itraconazole of VGI subtype was significantly lower than that of VGII subtype, and genes related to transporter activities were differentially expressed between VGI and VGII strains. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs (differential expressed genes) were found to be enriched in multiple ABC transporters. We further performed qPCR to quantify the expression level of seven ABC transporters. We found that ABC transporters ATM1, MDR1, PDR5, PDR5-3, and PXA2 were expressed significantly higher in VGII strains than in VGI strains. Our work revealed four novel ABC transporters, ATM1, PDR5, PDR5-3, and PXA2, promising candidate targets regulating azole susceptibility in C. gattii strains. LAY SUMMARY: Azoles were used as the primary antifungal agents for treating Cryptococuss gattii infection. Since subtypes of C. gattii respond differently to azoles. We analyzed mRNA expression profiles of different subtypes and identified four ABC transporters that could be potential genes regulating azole sensitivity.
Subject(s)
Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , ATP-Binding Cassette Transporters/genetics , Animals , Antifungal Agents/pharmacology , Azoles/pharmacology , Cryptococcosis/microbiology , Cryptococcosis/veterinary , Microbial Sensitivity Tests/veterinary , Multilocus Sequence Typing/veterinaryABSTRACT
Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China.
Subject(s)
Cryptococcosis , Cryptococcus gattii , Animals , Antifungal Agents , Cryptococcosis/microbiology , Genotype , Humans , Male , Mice , Molecular Epidemiology , Multilocus Sequence Typing , PhylogenyABSTRACT
OBJECTIVE: This study was performed to compare the radiologic characteristics and pathological presentations of primary pulmonary lymphoma (PPL), explore the possible mechanism underlying its development, summarize its radiologic characteristics, and improve the accuracy of its diagnosis. METHODS: The medical records of 22 patients pathologically diagnosed with PPL were retrospectively analyzed. RESULTS: Chest computed tomography (CT) demonstrated single or multiple nodules and masses in the lungs, patchy opacities or consolidation along the bronchovascular bundle, and no significantly enlarged mediastinal or hilar lymph nodes. All 22 cases of PPL were classified as non-Hodgkin's lymphoma (NHL) by transbronchial biopsy, CT-guided needle biopsy, and postoperative pathology. Most (16 cases) were marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). Twelve patients had air bronchograms within the lesion, and 13 showed ill-defined lesions with ground-glass brush-like changes. CONCLUSION: PPL is a rare lung tumor, and most are classified as MALT lymphoma, a subtype of NHL. Chest CT can help to diagnose this disease. Positron emission tomography (PET)/CT is of great clinical value for evaluation of the lesion and patient's general condition. The possibility of PPL should be considered in patients with characteristic CT and PET/CT findings and mild clinical symptoms, and early treatment should be administered.
Subject(s)
Lung Neoplasms , Lymphoma, B-Cell, Marginal Zone , Humans , Lung Neoplasms/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Positron Emission Tomography Computed Tomography , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
In the title coordination polymer, [Sr(C(16)H(13)O(3))(2)(H(2)O)(2)](n), the Sr(II) cation is eight-coordinated by six O atoms from four different 2-(3-benzoyl-phen-yl)propano-ate ligands and two O atoms of two water mol-ecules in a distorted dodeca-hedral geometry. Adjacent Sr(II) cations are bridged by two 2-(3-benzoyl-phen-yl)propano-ate ligands, forming an infinite chain along the b axis; the chains are further linked by inter-molecular O-H-O hydrogen bonds into a three-dimensional supra-molecular network.