Changjun Wang

Chinese Academy of Sciences, Peping, Beijing, China

Are you Changjun Wang?

Claim your profile

Publications (35)138.66 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Vascular endothelial growth factor receptor 2 (VEGFR2) is traditionally regarded as an important therapeutic target in a wide variety of malignancies, such as hepatocellular carcinoma (HCC). We previously generated a murine-human anti-VEGFR2 chimeric Fab (cFab), named FA8H1, which has the potential to treat VEGFR2-overexpressing solid tumors. Here, we investigated whether FA8H1 can be used as a carrier in molecularly targeted therapy in HCC xenograft models. FA8H1 was labeled with (131)I, and two HCC xenograft models were generated using BEL-7402 (high VEGFR2-expressing) and SMMC-7721 (low VEGFR2-expressing) cells, which were selected from five HCC cell lines. The biodistribution of (131)I-FA8H1 was determined in both models by Single-Photon Emission Computed Tomography and therapeutic effects were monitored in nude mice bearing BEL-7402 xenografts. Finally, we determined the involvement of necrosis and apoptotic pathways in treated mice using immunohistochemistry. (131)I-FA8H1 levels were dramatically reduced in blood and other viscera. The therapeutic effect of (131)I-labeled FA8H1 in the BEL-7402 model was significantly better than that by (131)I and FA8H1 alone. We observed extensive necrosis in the treated tumors, and both FasL and caspase 3 were up-regulated. Thus, (131)I-anti-VEGFR2 cFab has the potential to be used for molecularly targeted treatment of HCC overexpressing VEGFR2.
    Scientific Reports 05/2015; 5:10660. DOI:10.1038/srep10660 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We developed two assays based on one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) to identify Hantaan virus (HTNV) and Seoul virus (SEOV), members of the Hantavirus genus that cause hemorrhagic fever with renal syndrome (HFRS). Our results showed that these assays can be conducted within 30 min under isothermal conditions. The detection limit for HTNV was around 10 copies per reaction, similar to detection levels for quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. The detection limit for SEOV was 100 copies per reaction, a sensitivity that was 10-fold lower than that for qRT-PCR assays but 10-fold higher than that for RT-PCR assays. The method we developed was specific for both HTNV and SEOV without any cross-reaction with other pathogens.We conclude that RT-LAMP assays could be useful for the rapid and direct detection of HTNV and SEOV clinically, and for the epidemiological investigation of HFRS. Copyright © 2015. Published by Elsevier B.V.
    Journal of virological methods 04/2015; 124. DOI:10.1016/j.jviromet.2015.04.017 · 1.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcus suis, an emerging infectious pathogen, is the cause of two large-scale outbreaks of human streptococcal toxic shock syndrome in China, and has attracted much attention from the scientific community. The genetic basis of its pathogenesis remains enigmatic, and no effective prevention measures have been established. To better understand the virulence differentiation of S. suis and develop a promising vaccine, we isolated and sequenced a native avirulent S. suis strain (05HAS68). Animal experiments revealed that 05HAS68 is an avirulent strain and could protect piglets from the attack of virulent strains. Comparative genomics analyses demonstrated the genetic basis for the lack of virulence in 05HAS68, which is characterized by the absence of some important virulence-associated factors and the intact 89K pathogenicity island. Lack of virulence was also illustrated by reduced survival of 05HAS68 compared to a virulent strain in pig whole blood. Further investigations revealed a large-scale genomic rearrangement in 05HAS68, which was proposed to be mediated by transposase genes and/or prophages. This genomic rearrangement may have caused the genomic diversity of S. suis, and resulted in biological discrepancies between 05HAS68 and highly virulent S. suis strains.
    Scientific Reports 04/2015; 5:9835. DOI:10.1038/srep09835 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this research is to develop a human/murine chimeric Fab antibody which neutralizes the anthrax toxin, protective antigen (PA). The chimeric Fab was constructed using variable regions of murine anti-PA monoclonal antibody in combination with constant regions of human IgG. The chimeric PA6-Fab was expressed in E. coli. BL21 and evaluated by ELISA and co-immunoprecipitation- mass spectra. The potency of PA6-Fab to neutralize LeTx was examined in J774A.1 cell viability in vitro and in Fisher 344 rats in vivo. The PA6-Fab did not have domain similarity corresponding to the current anti PA mAbs, but specifically bound to anthrax PA at an affinity of 1.76 nM, and was able to neutralize LeTx in vitro and protected 56.9% cells at 20 μg/mL against anthrax LeTx. One hundred μg PA6-Fab could neutralize 300 μg LeTx in vivo. The PA6-Fab has potential as a therapeutic mAb for treatment of anthrax.
    International Journal of Molecular Sciences 10/2014; 15(10):18496-18507. DOI:10.3390/ijms151018496 · 2.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcus suis (S. suis) is a family of pathogenic gram-positive bacterial strains that represents a primary health problem in the swine industry worldwide. S. suis is also an emerging zoonotic pathogen that causes severe human infections clinically featuring with varied diseases/syndromes (such as meningitis, septicemia, and arthritis). Over the past few decades, continued efforts have made significant progress toward better understanding this zoonotic infectious entity, contributing in part to the elucidation of the molecular mechanism underlying its high pathogenicity. This review is aimed at presenting an updated overview of this pathogen from the perspective of molecular epidemiology, clinical diagnosis and typing, virulence mechanism, and protective antigens contributing to its zoonosis.
    Virulence 03/2014; 5(4). DOI:10.4161/viru.28595 · 3.32 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain (EMD) was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor-xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA-MB-231 cells in a dose dependent manner. The expression caspase-3 was activated, and the expression of Bcl-2 was reduced while that of Bax was elevated in MDA-MB-231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl-2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab which was isolated successfully in this research is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 03/2014; 134(5). DOI:10.1002/ijc.28451 · 5.01 Impact Factor
  • The Journal of infection 02/2014; 69(1). DOI:10.1016/j.jinf.2014.02.010 · 4.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcal pathogens have evolved to express exoglycosidases, one of which is BgaC β-galactosidase, to deglycosidate host surface glycolconjucates with exposure of the polysaccharide receptor for bacterial adherence. The paradigm BgaC protein is the bgaC product of Streptococcus, a bacterial surface-exposed β-galactosidase. Here we report the functional definition of the BgaC homologue from an epidemic Chinese strain 05ZYH33 of the zoonotic pathogen Streptococcus suis. Bioinformatics analyses revealed that S. suis BgaC shared the conserved active sites (W240, W243 and Y454). The recombinant BgaC protein of S. suis was purified to homogeneity. Enzymatic assays confirmed its activity of β-galactosidase. Also, the hydrolysis activity was found to be region-specific and sugar-specific for the Gal β-1,3-GlcNAc moiety of oligosaccharides. Flow cytometry analyses combined with immune electron microscopy demonstrated that S. suis BgaC is an atypical surface-anchored protein in that it lacks the "LPXTG" motif for typical surface proteins. Integrative evidence from cell lines and mice-based experiments showed that an inactivation of bgaC does not significantly impair the ability of neither adherence nor anti-phagocytosis, and consequently failed to attenuate bacterial virulence, which is somewhat similar to the scenario seen with S. pneumoniae. Therefore we concluded that S. suis BgaC is an atypical surface-exposed protein without the involvement of bacterial virulence.
    Scientific Reports 02/2014; 4:4140. DOI:10.1038/srep04140 · 5.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcus suis (S. suis) is an important zoonotic pathogen that causes multiple diseases in both pigs and humans. Many studies suggest that Streptococcus utilizes host extracellular matrix proteins, including laminin, for adhesion and invasion of host cells. Recently, we identified a putative Lmb protein (CDS 0330) of a highly virulent strain of S. suis (serotype 2). In this study, we characterized the ability of CDS 0330 to bind human laminin, and evaluated the protective efficacy of a recombinant protein vaccine. Bioinformatic analysis revealed that both the amino acid sequence and tertiary structure of CDS 0330 were similar to Lmb proteins in other Streptococcus. In addition, the sequence of CDS 0330 was present in the genomes of 26 of the 38 sequenced streptococci species, indicating an early origin and conservation of this gene. Particularly, all 17 sequenced S. suis genomes, regardless of serotype or geographic origin, contained CDS 0330 gene in their genome with a minimum pair-wise amino acid identity of 92%. PCR amplification revealed that CDS 0330 gene is distributed throughout 35 S. suis serotypes in the lmb-htp format. Flow cytometry analysis confirmed that CDS 0330 was expressed on the cell surface of S. suis, and ELISA revealed the recombinant CDS 0330 protein could bind laminin in vitro. Finally, vaccinating mice with recombinant CDS 0330 protein significantly prolonged survival after S. suis infection. Together, these data reveal that CDS 0330 is a laminin binding protein of S. suis 2, and open new avenues for preventing S. suis 2 infection.
    Microbiological Research 09/2013; 169(5-6):395-401. DOI:10.1016/j.micres.2013.09.007 · 1.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: An epidemic of human H7N9 influenza virus infection has recently emerged in China, which was clinically featuring with high mortality and while also resulting in serious economic loss. The novel reassortant avian-origin influenza A (H7N9) virus, as the causative agent of this epidemic, raised the possibility of triggering a large-scale of flu pandemic worldwide. It seemed likely that fast molecular detection assays specific for this viruses would be in great demand. Here we report a one-step RT-LAMP method for rapid detection of HA gene and NA gene of H7N9 virus, the minimum detection limit of which was evaluated using in vitro transcription RNA templates. Totally, 135 samples from clinical specimens (from either patients or poultry) were subjected to testing by this method in comparison with the real time PCR recommend by the World Health Organization (WHO). Our results showed that 1) RT-LAMP-based trials can be completed in 12∼23 minute, 2) detection limit for H7 gene is around 10 copies per reaction, which is similar to that of the real time PCR whereas that for its counterpart N9 gene is 5 copies per reaction with a 100-fold higher sensitivity than the WHO recommended-method. Indeed, this excellent performance of our method was also validated by a series of clinical specimens. Therefore we believe that the simple, fast and sensitive method of RT-LAMP might be widely applied in the field detection for H7N9 infections and play a role in prevention of an influenza pandemic.
    Journal of clinical microbiology 09/2013; 51(11). DOI:10.1128/JCM.01907-13 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that causes considerable economic losses to the pig industry and significantly threatens public health worldwide. The highly pathogenic S. suis 2, which contains the 89K pathogenicity island (PAI), has caused large-scale outbreaks of infections in human, with a high mortality rate. In this study, we established two loop-mediated isothermal amplification (LAMP)-based assays that can rapidly detect S. suis 2 and the 89K PAI and be performed simultaneously under the same conditions. Further, based on the findings of these two LAMP assays and using the same set of serially diluted DNA, we compared the sensitivities of different LAMP product detection methods, including SYBR Green detection, gel electrophoresis, turbidimetry, calcein assays, and hydroxynaphthol blue detection. The results suggested that target genes could be amplified and detected within 48 min under 63°C isothermal conditions. The sensitivity of S. suis 2 detection varies among detection methods and under different reaction systems, indicating that for each LAMP reaction system, multiple detection methods should be performed for the selection of an optimal detection method. The sensitivities of the optimized methods (7.16 copies/reaction) in the present study were identical to those of real-time polymerase chain reaction, and the test results for reference strains and clinical samples i showed that these LAMP systems have high specificity. Thus, since the LAMP systems established in this study are simple, fast, and sensitive, they may have good clinical potential for detecting the highly pathogenic S. suis 2.
    Journal of clinical microbiology 07/2013; 51(10). DOI:10.1128/JCM.01183-13 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: c-Met is over-expressed in hepatocellular carcinoma(HCC) but is absent or expressed at low levels in normal tissues. Therefore we generated a novel conjugate of a human anti-c-Met Fab fragment (MetFab) with doxorubicin (DOX) and assessed whether it had targeted antitumor activity against HCC and reduced the side-effects of DOX. The MetFab was screened from human phage library, conjugated with DOX via chemical synthesis, and the conjugation MetFab-DOX was confirmed by HPLC. The drug release patterns, the binding efficacy, and cellular distribution of MetFab-DOX were assessed. MetFab-DOX was stable at pH7.2 PBS while release doxorubicin quickly at pH4.0, the binding efficacy of MetFab-DOX was similarly as MetFab, and the cellular distribution of the MetFab-DOX is distinct from free DOX. The cytotoxicity of MetFab-DOX was analyzed by the MTT method and the nude mouse HCC model. The MetFab-DOX demonstrated cytotoxic effects on c-Met expressing-tumor cells, but not on the cells without c-Met expression. MetFab-DOX exerted anti-tumor effect and significantly reduced the side effect of free DOX in mice model. Furthermore, the localization of conjugate was confirmed by immunofluorescence staining of tumor tissue sections and optical tumor imaging, respectively, and the tissue-distribution of drug was compared between free DOX and MetFab-DOX treatment by spectrofluorometer. MetFab-DOX can localize to the tumor tissue, and the concentration of doxorubicin in the tumor was higher after MetFab-DOX administration than after DOX administration. In summary, MetFab-DOX can target c-Met expressing HCC cells effectively and have obvious antitumor activity with decreased side-effects in preclinical models of HCC.
    PLoS ONE 05/2013; 8(5):e63093. DOI:10.1371/journal.pone.0063093 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: NeuB, a sialic acid synthase catalyzes the last committed step of the de novo biosynthetic pathway of sialic acid, a major element of bacterial surface structure. Here we report a functional NeuB homologue of Streptococcus suis, a zoonotic agent, and systematically address its molecular and immunological role in bacterial virulence. Disruption of neuB led to thinner capsules and more susceptibility to pH, and cps2B inactivation resulted in complete absence of capsular polysaccharides. These two mutants both exhibited increased adhesion and invasion to Hep-2 cells and improved sensibility to phagocytosis. Not only do they retain the capability of inducing the release of host pro-inflammatory cytokines, but also result in the faster secretion of IL-8. Easier cleaning up of the mutant strains in whole blood is consistent with virulence attenuation seen with experimental infections of both mice and SPF-piglets. Therefore we concluded that altered architecture of S. suis surface attenuates its virulence.
    Scientific Reports 10/2012; 2:710. DOI:10.1038/srep00710 · 5.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We clarified the pathogenic influence of the absence of Streptococcus suis type 2 capsular saliva acid on BLAB/c mice. The virulence of the experimental strains were compared; the distribution of strains in vivo was determined by quantitative plating. Histopathological analysis was used to qualitatively compare the different pathogenicity of wild strain and knockout strains. ELISA was used to test the levels of cytokine in whole blood cells for the stimulation of strains. The virulence of mutant strains was significantly reduced, and when the genes were restored, toxicity levels were recovered to that of the wild type strain. The distribution in blood and in the brain between wild strain and knock out strains has significant difference, and Streptococcus suis type 2 strains can cause different degrees of brain damage. During the in vitro test, the mutant strains can stimulate the whole blood cells to secrete higher levels of MCP-1 and IL-6. Capsular saliva acid affects bacterial virulence and host cell inflammation response. As an important virulence factor of Streptococcus suis type 2, it can damage the blood brain barrier and cause meningitis.
    ACTA MICROBIOLOGICA SINICA 04/2012; 52(4):498-504.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Quorum sensing is a widespread chemical communication in response to fluctuation of bacterial population density, and has been implicated into bacterial biofilm formation and regulation of expression of virulence factors. The luxS gene product, S-ribosylhomocysteinase, catalizes the last committed step in biosynthetic pathway of autoinducer 2 (AI-2), a signaling molecule for inter-species quorum sensing. We found a luxS homologue in 05ZYH33, an epidemic strain of Streptococcus suis serotype 2 (SS2) in China. A luxS null mutant (ΔluxS) of 05ZYH33 strain was obtained using an approach of homologous recombination. LuxS was determined to be required for AI-2 production in 05ZYH33 strain of S. suis 2. Inactivation of luxS gene led to a wide range of phenotypic changes including thinner capsular walls, increased tolerance to H(2)O(2), reduced adherence capacity to epithelial cells, etc. In particular, loss of LuxS impaired dramatically its full virulence of SS2 in experimental model of piglets, and functional complementation restored it nearly to the level of parent strain. Genome-wide transcriptome analyses suggested that some known virulence factors such as CPS are down-regulated in the ΔluxS mutant, which might in part explain virulence attenuation by luxS deletion. Similarly, 29 of 71 genes with different expression level were proposed to be targets candidate regulated by LuxS/AI-2-dependent quorum sensing.
    The Journal of Microbiology 12/2011; 49(6):1000-11. DOI:10.1007/s12275-011-1523-1 · 1.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our previous studies revealed that a new disease form of streptococcal toxic shock syndrome (STSS) is associated with specific Streptococcus suis serotype 2 (SS2) strains. To achieve a better understanding of the pathogenicity and evolution of SS2 at the whole-genome level, comparative genomic analysis of 18 SS2 strains, selected on the basis of virulence and geographic origin, was performed using NimbleGen tiling arrays. Our results demonstrate that SS2 isolates have highly divergent genomes. The 89K pathogenicity island (PAI), which has been previously recognized as unique to the Chinese epidemic strains causing STSS, was partially included in some other virulent and avirulent strains. The ABC-type transport systems, encoded by 89K, were hypothesized to greatly contribute to the catastrophic features of STSS. Moreover, we identified many polymorphisms in genes encoding candidate or known virulence factors, such as PlcR, lipase, sortases, the pilus-associated proteins, and the response regulator RevS and CtsR. On the basis of analysis of regions of differences (RDs) across the entire genome for the 18 selected SS2 strains, a model of microevolution for these strains is proposed, which provides clues into Streptococcus pathogenicity and evolution. Our deep comparative genomic analysis of the 89K PAI present in the genome of SS2 strains revealed details into how some virulent strains acquired genes that may contribute to STSS, which may lead to better environmental monitoring of epidemic SS2 strains.
    BMC Genomics 05/2011; 12:219. DOI:10.1186/1471-2164-12-219 · 4.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recombinant antibody phage display technology has been used to mimic many aspects of the processes that govern the generation and selection of high-affinity natural human antibodies in the human immune system, especially for infectious disease prophylaxis. An anti-rabies virus immunized phage-display Fab library was constructed from peripheral blood lymphocytes from vaccinated volunteers. The immunized antibody library, with a diversity of 6.7×10(8), was used to select and produce antibodies that bound to rabies virus glycoprotein. After five rounds of immobilized fixed rabies virion panning, four unique DNA sequences were found in the higher binding clones, and only one, Fab094, showed neutralization activity. Fab094 components were analyzed by ELISA, immunoprecipitation and immunofluorescent staining. ELISA and immunofluorescence showed that Fab094 bound specifically to rabies virions. Immunoprecipitation and mass spectrometry showed that Fab094 reacted with rabies virus glycoprotein. To improve the penetration power of Fab094 antibodies, we developed Fab094 calcium phosphate nanoparticles (Fab094-CPNPs) and tested their efficacy. The rapid fluorescent focus inhibition test indicated that the neutralizing antibody titers of Fab094 and Fab094-CPNPs were reached at 200.17 IU/Kg and 246.12 IU/Kg, respectively. These findings were confirmed in vivo in a Kunming mouse challenge model. Our results demonstrate that human Fab094 and Fab094-CPNPs are efficacious candidate drugs to replace rabies immunoglobulin in post-exposure prophylaxis (PEP).
    PLoS ONE 05/2011; 6(5):e19848. DOI:10.1371/journal.pone.0019848 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Streptococcus suis 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. In this study, we investigated the functionality of one of Streptococcus suis 2 sortases, known as the srtBCD. To obtain the isogenic mutant srtBCD, the competent cells of 05ZYH33 were subjected to electrotrans formation with recombinant plasmid based on the principle of homologous recombination. The resulting mutant strains was further confirmed by a series of PCR and reverse transcription PCR. To better assess the role of srtBCD gene in the virulence of 05ZYH33, cell adherence assays and experimental infection of mice was adopted. A SrtBCD defective mutant of 05ZYH33 was found to be associated with growth curve upon cultivation in standard laboratory used in our in vitro assays. Furthermore, abolishment of the expression of srtBCD result in impaired interactions of S. suis with human laryngeal epithelial cell line. However, there is no differences when infection mice by the WT and mutant strain. These results suggest that srtBCD are critical for the pathogen-host interaction of S. suis 2, but abolishment of srtBCD does not impair the full virulence of 05ZYH33. It is to expect that future study carried out with S. suis 2 to verification the conclusions.
    ACTA MICROBIOLOGICA SINICA 03/2011; 51(3):386-92.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Rgg-like regulators, a family of transcription factors commonly found in many Gram-positive bacteria, play multiple roles, especially in the control of pathogen virulence. Here, we report an rgg homologue from a Chinese isolate, 05ZYH33, of Streptococcus suis serotype 2 (SS2). Deletion of the rgg gene in SS2 increased its adhesion to Hep-2 cells and hemolytic activity in vitro. Significantly, inactivation of the rgg gene attenuated SS2 virulence in an experimental piglet infection model. Using DNA microarrays and quantitative reverse transcription-PCR, we found that the Rgg regulator affects the transcriptional profile of 15.87% (n = 345) of all of the annotated chromosomal genes, including those involved in nonglucose carbohydrate metabolism, DNA recombination, protein biosynthesis, bacterial defense mechanisms, and others. It was experimentally verified that the deletion of rgg in SS2 reduced the utilization of nonglucose carbohydrates, such as lactose and maltose. In addition, the rgg gene was found to be associated with changes in the bacterial microscopic phenotype and growth curve. These data suggested that Rgg in SS2 is a global transcriptional regulator that plays an important role in promoting SS2 bacterial survival during pathogen-host interaction.
    Infection and immunity 03/2011; 79(3):1319-28. DOI:10.1128/IAI.00193-10 · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pathogenicity islands (PAIs), a distinct type of genomic island (GI), play important roles in the rapid adaptation and increased virulence of pathogens. 89K is a newly identified PAI in epidemic Streptococcus suis isolates that are related to the two recent large-scale outbreaks of human infection in China. However, its mechanism of evolution and contribution to the epidemic spread of S. suis 2 remain unknown. In this study, the potential for mobilization of 89K was evaluated, and its putative transfer mechanism was investigated. We report that 89K can spontaneously excise to form an extrachromosomal circular product. The precise excision is mediated by an 89K-borne integrase through site-specific recombination, with help from an excisionase. The 89K excision intermediate acts as a substrate for lateral transfer to non-89K S. suis 2 recipients, where it reintegrates site-specifically into the target site. The conjugal transfer of 89K occurred via a GI type IV secretion system (T4SS) encoded in 89K, at a frequency of 10(-6) transconjugants per donor. This is the first demonstration of horizontal transfer of a Gram-positive PAI mediated by a GI-type T4SS. We propose that these genetic events are important in the emergence, pathogenesis and persistence of epidemic S. suis 2 strains.
    Molecular Microbiology 03/2011; 79(6):1670-83. DOI:10.1111/j.1365-2958.2011.07553.x · 5.03 Impact Factor

Publication Stats

723 Citations
138.66 Total Impact Points

Institutions

  • 2011
    • Chinese Academy of Sciences
      • Key Laboratory of Pathogenic Microbiology and Immunology
      Peping, Beijing, China
  • 2009
    • Nanjing Normal University
      • College of Life Sciences
      Nan-ching, Jiangsu Sheng, China
  • 2008
    • Nanjing Medical University
      • Department of Pathogenic Biology
      Nan-ching, Jiangsu Sheng, China
    • Third Military Medical University
      • Department of Microbiology
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2007
    • Beijing Institute of Microbiology and Epidemiology
      Peping, Beijing, China