BackgroundIdiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease.MethodsIn this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls.ResultsA total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC analysis.ConclusionsOur results provided vital information regarding lipid metabolism in IPF patients and more importantly, a few potentially promising biomarkers were firstly identified which may have a predictive role in monitoring and diagnosing IPF disease.Electronic supplementary materialThe online version of this article (10.1186/s12890-017-0513-4) contains supplementary material, which is available to authorized users.
Background:The pneumococcal endo--N-acetylglucosaminidase LytB is required for cell division and colonization. Results: Structural analysis revealed that the catalytic domain of LytB consists of three structurally distinct modules. Conclusion: All three modules of LytB are necessary for its optimal activity toward peptidoglycan hydrolysis and for pneumococcal adhesion to respiratory epithelial cells. Significance: Provided is the structural insight into LytB-mediated pneumococcal cell wall remodeling and pathogenesis.
e Streptococcus pneumoniae is a major bacterial pathogen in humans. Its polysaccharide capsule is a key virulence factor that promotes bacterial evasion of human phagocytic killing. While S. pneumoniae produces at least 94 antigenically different types of capsule, the genes for biosynthesis of almost all capsular types are arranged in the same locus. The transcription of the capsular polysaccharide (cps) locus is not well understood. This study determined the transcriptional features of the cps locus in the type 2 virulent strain D39. The initial analysis revealed that the cps genes are cotranscribed from a major transcription start site at the ؊25 nucleotide (G) upstream of cps2A, the first gene in the locus. Using unmarked chromosomal truncations and a luciferasebased transcriptional reporter, we showed that the full transcription of the cps genes not only depends on the core promoter immediately upstream of cps2A, but also requires additional elements upstream of the core promoter, particularly a 59-bp sequence immediately upstream of the core promoter. Unmarked deletions of these promoter elements in the D39 genome also led to significant reduction in CPS production and virulence in mice. Lastly, common cps gene (cps2ABCD) mutants did not show significant abnormality in cps transcription, although they produced significantly less CPS, indicating that the CpsABCD proteins are involved in the encapsulation of S. pneumoniae in a posttranscriptional manner. This study has yielded important information on the transcriptional characteristics of the cps locus in S. pneumoniae. Streptococcus pneumoniae (pneumococcus) is a major cause of bacterial infections in humans, including otitis media, pneumonia, bacteremia, and meningitis (1). As the outermost structure, the capsule is the major virulence factor of S. pneumoniae and protects the bacterium by interfering with host phagocytic killing (2). Virtually all of the clinical isolates are encapsulated, and mutations in the cps locus result in the loss of virulence (3). The capsule of S. pneumoniae is composed of capsular polysaccharides (CPSs). The CPSs are immunogenic and thus serve as the target antigens for the current pneumococcal vaccines (4). Due to host immune selection that targets the capsule, the CPSs have undergone extensive chemical and antigenic variation via genetic diversity in the CPS biosynthesis genes. At least 94 antigenically distinct capsular serotypes have been identified in S. pneumoniae (5, 6). While the CPSs of types 3 and 37 are produced as relatively simple repeats of polysaccharides by the synthase pathway (7, 8), all other capsule types are much more complex and are synthesized by WZY-dependent polymerization, a mechanism of capsule production that is widely found in other bacteria (9-11).Except for type 37, all of the CPS types in S. pneumoniae are determined by a set of capsule biosynthesis genes, which are historically designated cps or cap (12). Bentley et al. recently renamed the pneumococcal capsule genes on the basis of their overall...
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The polysaccharide capsule is the major virulence factor of Streptococcus pneumoniae (pneumococcus), a major human pathogen. The sequences in the promoter and coding regions of the capsule gene locus undergo extensive variations through the natural transformation-mediated horizontal gene transfer. The sequence variations in the coding region have led to at least 97 capsular serotypes. However, it remains unclear whether the sequence polymorphisms in the promoter region have any biological significance. In this study, we determined the sequences of the cps promoter region from 225 invasive pneumococcal isolates, and identified modular composition and remarkable inter-strain sequence variations in this region. The strain-to strain variations in the cps promoter are characterized by diversity in sequence and size, mosaic combinations of nucleotide polymorphisms and sequence modules, selective preservation of the sequence combinations, and promiscuous assortments of the sequences between the promoter and coding regions. Isogenic pneumococci carrying allelic variants of the cps promoter displayed significant differences in the transcription of the capsule genes, capsule production, adhesion to host epithelial cells, anti-phagocytosis and virulence in mouse bacteremia model. This study has thus indicated that the sequence polymorphisms in the cps promoter represent a novel mechanism for fine-tuning the level of encapsulation and virulence among S. pneumoniae strains.
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