A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates

BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ∼89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections

Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 ( S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure. METHODS AND FINDINGS: We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks. CONCLUSIONS: We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study

SalK/SalR, a Two-Component Signal Transduction System, Is Essential for Full Virulence of Highly Invasive Streptococcus suis Serotype 2

BACKGROUND: Streptococcus suis serotype 2 (S. suis 2, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of salKR eliminated the lethality of SS2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant DeltasalKR restored its soaring pathogenicity. Colonization experiments showed that the DeltasalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the DeltasalKR mutant. CONCLUSIONS/SIGNIFICANCE: These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI

MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies

Remotely sensed rice yield prediction using multi-temporal NDVI data derived from NOAA's-AVHRR.

Grain-yield prediction using remotely sensed data have been intensively studied in wheat and maize, but such information is limited in rice, barley, oats and soybeans. The present study proposes a new framework for rice-yield prediction, which eliminates the influence of the technology development, fertilizer application, and management improvement and can be used for the development and implementation of provincial rice-yield predictions. The technique requires the collection of remotely sensed data over an adequate time frame and a corresponding record of the region's crop yields. Longer normalized-difference-vegetation-index (NDVI) time series are preferable to shorter ones for the purposes of rice-yield prediction because the well-contrasted seasons in a longer time series provide the opportunity to build regression models with a wide application range. A regression analysis of the yield versus the year indicated an annual gain in the rice yield of 50 to 128 kg ha(-1). Stepwise regression models for the remotely sensed rice-yield predictions have been developed for five typical rice-growing provinces in China. The prediction models for the remotely sensed rice yield indicated that the influences of the NDVIs on the rice yield were always positive. The association between the predicted and observed rice yields was highly significant without obvious outliers from 1982 to 2004. Independent validation found that the overall relative error is approximately 5.82%, and a majority of the relative errors were less than 5% in 2005 and 2006, depending on the study area. The proposed models can be used in an operational context to predict rice yields at the provincial level in China. The methodologies described in the present paper can be applied to any crop for which a sufficient time series of NDVI data and the corresponding historical yield information are available, as long as the historical yield increases significantly

Pioneering Piezoelectric-Driven Atomic Hydrogen for Efficient Dehalogenation of Halogenated Organic Pollutants

The electrocatalytic hydrodehalogenation (EHDH) process mediated by atomic hydrogen (H*) is recognized as an efficient method for degrading halogenated organic pollutants (HOPs). However, a significant challenge is the excessive energy consumption resulting from the recombination of H* to H2 production in the EHDH process. In this study, a promising strategy was proposed to generate piezo-induced atomic H*, without external energy input or chemical consumption, for the degradation and dehalogenation of HOPs. Specifically, sub-5 nm Ni nanoparticles were subtly dotted on an N-doped carbon layer coating on BaTiO3 cube, and the resulted hybrid nanocomposite (Ni-NC@BTO) can effectively break C-X (X = Cl and F) bonds under ultrasonic vibration or mechanical stirring, demonstrating high piezoelectric driven dehalogenation efficiencies toward various HOPs. Mechanistic studies revealed that the dotted Ni nanoparticles can efficiently capture H* to form Ni–H* (Habs) and drive the dehalogenation process to lower the toxicity of intermediates. COMSOL simulations confirmed a “chimney effect” on the interface of Ni nanoparticle, which facilitated the accumulation of H+ and enhanced electron transfer for H* formation by improving the surface charge of the piezocatalyst and strengthening the interfacial electric field. Our work introduces an environmentally friendly dehalogenation method for HOPs using the piezoelectric process independent of the external energy input and chemical consumption

Novel Hydroxyapatite Whiskers Modified by Silver Ion and Nano Zinc Oxide Used for Bone Defect Repairment

The hydroxyapatite (HA) is widely used as bone tissue repair material. The improvement of the antibacterial performance is an aroused general interest. In the present study, the silver ion and nano-zinc oxide modified hydroxyapatite whiskers (HAw) were successfully prepared. The microstructure and the composition of the modified HAw were analyzed by Field Emission Scanning Electron Microscopy (FESEM) and X-ray diffractometer (XRD). SEM analysis showed that the length of the whiskers was 70–190 μm, and the aspect ratio was 10–60. With the increase of Ag+ content, the length and aspect ratio of the whiskers gradually decreased and incomplete spherical hydroxyapatite appeared. FEEM analysis showed that nano-zinc oxide particles on ZnO/3Ag-HAw surface are evenly distributed; the average particle size is less than 30 nm. XRD analysis showed that after sol-gel and calcination treatment, the nano-zinc oxide phase appeared in the diffraction pattern of ZnO/Ag-HAw. TEM analysis showed that the interplanar spacing of 5Ag-HAw increased slightly. The CCK-8 and cells co-culture assays were used to assess the proliferation and differentiation of MC3T3-E1 cells, respectively. The antibacterial abilities of the modified HAw against E. coli (ATCC25922) and S. aureus (ATCC6538) were investigated. The cell cytotoxicity test showed that the cytotoxicity level was 0, and there was no cytotoxicity. Cell adhesion experiments showed that ZnO/3Ag-HAw has good cell compatibility and biological activity. The modified hawthorn has a bacteriostatic rate of more than 90% and has good bacteriostatic activity