Lilian Sun

VFDB: a reference database for bacterial virulence factors

Bacterial pathogens continue to impose a major threat to public health worldwide in the 21st century. Intensified studies on bacterial pathogenesis have greatly expanded our knowledge about the mechanisms of the disease processes at the molecular level over the last decades. To facilitate future research, it becomes necessary to form a database collectively presenting the virulence factors (VFs) of various medical significant bacterial pathogens. The aim of virulence factor database (VFDB) (http://www.mgc.ac.cn/VFs/) is to provide such a source for scientists to rapidly access to current knowledge about VFs from various bacterial pathogens. VFDB is comprehensive and user-friendly. One can search VFDB by browsing each genus or by typing keywords. Furthermore, a BLAST search tool against all known VF-related genes is also available. VFDB provides a unified gateway to store, search, retrieve and update information about VFs from various bacterial pathogens.

VFDB 2012 update: toward the genetic diversity and molecular evolution of bacterial virulence factors

The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) has served as a comprehensive repository of bacterial virulence factors (VFs) for >7 years. Bacterial virulence is an exciting and dynamic field, due to the availability of complete sequences of bacterial genomes and increasing sophisticated technologies for manipulating bacteria and bacterial genomes. The intricacy of virulence mechanisms offers a challenge, and there exists a clear need to decipher the ‘language’ used by VFs more effectively. In this article, we present the recent major updates of VFDB in an attempt to summarize some of the most important virulence mechanisms by comparing different compositions and organizations of VFs from various bacterial pathogens, identifying core components and phylogenetic clades and shedding new light on the forces that shape the evolutionary history of bacterial pathogenesis. In addition, the 2012 release of VFDB provides an improved user interface.

Virome Analysis for Identification of Novel Mammalian Viruses in Bat Species from Chinese Provinces

ABSTRACT Bats are natural hosts for a large variety of zoonotic viruses. This study aimed to describe the range of bat viromes, including viruses from mammals, insects, fungi, plants, and phages, in 11 insectivorous bat species (216 bats in total) common in six provinces of China. To analyze viromes, we used sequence-independent PCR amplification and next-generation sequencing technology (Solexa Genome Analyzer II; Illumina). The viromes were identified by sequence similarity comparisons to known viruses. The mammalian viruses included those of the Adenoviridae, Herpesviridae, Papillomaviridae, Retroviridae, Circoviridae, Rhabdoviridae, Astroviridae, Flaviridae, Coronaviridae, Picornaviridae, and Parvovirinae; insect viruses included those of the Baculoviridae, Iflaviridae, Dicistroviridae, Tetraviridae, and Densovirinae; fungal viruses included those of the Chrysoviridae, Hypoviridae, Partitiviridae, and Totiviridae; and phages included those of the Caudovirales, Inoviridae, and Microviridae and unclassified phages. In addition to the viruses and phages associated with the insects, plants, and bacterial flora related to the diet and habitation of bats, we identified the complete or partial genome sequences of 13 novel mammalian viruses. These included herpesviruses, papillomaviruses, a circovirus, a bocavirus, picornaviruses, a pestivirus, and a foamy virus. Pairwise alignments and phylogenetic analyses indicated that these novel viruses showed little genetic similarity with previously reported viruses. This study also revealed a high prevalence and diversity of bat astroviruses and coronaviruses in some provinces. These findings have expanded our understanding of the viromes of bats in China and hinted at the presence of a large variety of unknown mammalian viruses in many common bat species of mainland China.

VFDB 2008 release: an enhanced web-based resource for comparative pathogenomics

Virulence factor database (VFDB) was set up in 2004 dedicated for providing current knowledge of virulence factors (VFs) from various medical significant bacterial pathogens to facilitate pathogenomic research. Nowadays, complete genome sequences of almost all the major pathogenic microbes have been determined, which makes comparative genomics a powerful approach for uncovering novel virulence determinants and hidden aspects of pathogenesis. VFDB was therefore upgraded to present the enormous diversity of bacterial genomes in terms of virulence genes and their organization. The VFDB 2008 release includes the following new features; (i) detailed tabular comparison of virulence composition of a given genome with other genomes of the same genus, (ii) multiple alignments and statistical analysis of homologous VFs and (iii) graphical comparison of genomic organizations of virulence genes. Comparative analysis of the numerous VFs will improve our understanding of the nature and evolution of virulence, as well as the development of new therapeutic and preventive strategies. VFDB 2008 release offers more user-friendly tools for comparative pathogenomics and it is publicly accessible at http://www.mgc.ac.cn/VFs/.

Unbiased Parallel Detection of Viral Pathogens in Clinical Samples by Use of a Metagenomic Approach

ABSTRACT Viral infectious diseases represent a major threat to public health and are among the greatest disease burdens worldwide. Rapid and accurate identification of viral agents is crucial for both outbreak control and estimating regional disease burdens. Recently developed metagenomic methods have proven to be powerful tools for simultaneous pathogen detection. Here, we performed a systematic study of the capability of the short-read-based metagenomic approach in the molecular detection of viral pathogens in nasopharyngeal aspirate samples from patients with acute lower respiratory tract infections (n = 16). Using the high-throughput capacity of ultradeep sequencing and a dedicated data interpretation method, we successfully identified seven species of known respiratory viral agents from 15 samples, a result that was consistent with results of conventional PCR assays. We also detected a coinfected case that was missed by regular PCR testing. Using the metagenomic data, 11 draft genomes of the abundantly detected viruses in the samples were reconstructed with 21.84% to 98.53% coverage. Our results show the power of the short-read-based metagenomic approach for accurate and parallel screening of viral pathogens. Although there are some inherent difficulties in applying this approach to clinical samples, including a lack of controls, limited specimen quantity, and high contamination rate, our work will facilitate further application of this unprecedented high-throughput method to clinical samples.

Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a

BackgroundShigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).ResultsThe Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes.ConclusionOur data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.

Deciphering the bat virome catalog to better understand the ecological diversity of bat viruses and the bat origin of emerging infectious diseases

Studies have demonstrated that ~60%–80% of emerging infectious diseases (EIDs) in humans originated from wild life. Bats are natural reservoirs of a large variety of viruses, including many important zoonotic viruses that cause severe diseases in humans and domestic animals. However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. The purpose of this study was to survey the ecological and biological diversities of viruses residing in these bat species, to investigate the presence of potential bat-borne zoonotic viruses and to evaluate the impacts of these viruses on public health. The data obtained in this study revealed an overview of the viral community present in these bat samples. Many novel bat viruses were reported for the first time and some bat viruses closely related to known human or animal pathogens were identified. This genetic evidence provides new clues in the search for the origin or evolution pattern of certain viruses, such as coronaviruses and noroviruses. These data offer meaningful ecological information for predicting and tracing wildlife-originated EIDs.

The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination.

BackgroundConidia are considered to be the primary cause of infections by Trichophyton rubrum.ResultsWe have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions.ConclusionOur results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum.

Complete Genome Sequence of the Nitrogen-Fixing and Rhizosphere-Associated Bacterium Pseudomonas stutzeri Strain DSM4166

We present here the analysis of the whole-genome sequence of Pseudomonas stutzeri strain DSM4166, a diazotrophic isolate from the rhizosphere of a Sorghum nutans cultivar. To our knowledge, this is the second genome to be sequenced for P. stutzeri. The availability and analysis of the genome provide insight into the evolution of the nitrogen fixation property and identification of rhizosphere competence traits required in interactions with host plants.

ShiBASE: an integrated database for comparative genomics of Shigella

Among the major enteric bacterial pathogens, Shigella is found to display extreme genome diversity and dynamics, which imposes a challenge in comparative genomic studies. To facilitate further studies in this area, we have constructed an integrated online database, ShiBASE (http://www.mgc.ac.cn/ShiBASE/),which contains Shigella genomic sequences of four species and additional comparative genomic hybridization (CGH) data of 43 serotypes. ShiBASE offers online comparative analysis on DNA sequences, gene orders, metabolic pathways and virulence factors. In addition, ShiBASE has a newly developed online comparative visualization service, Shi-align, which enables the alignment of any query sequence with the reference genome sequences.Among the major enteric bacterial pathogens, Shigella is found to display extreme genome diversity and dynamics, which imposes a challenge in comparative genomic studies. To facilitate further studies in this area, we have constructed an integrated online database, ShiBASE (),which contains Shigella genomic sequences of four species and additional comparative genomic hybridization (CGH) data of 43 serotypes. ShiBASE offers online comparative analysis on DNA sequences, gene orders, metabolic pathways and virulence factors. In addition, ShiBASE has a newly developed online comparative visualization service, Shi-align, which enables the alignment of any query sequence with the reference genome sequences.