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ABSTRACT: Aim: To explore the transcriptional regulation of the psaEF and psaABC loci by the RovA and PhoP regulators in Yersinia pestis. Materials & methods: Primer extension, LacZ fusion, gel mobility shift and DNase I footprinting assays were conducted in combination for this gene regulation study. Results: It was determined that PhoP and RovA recognized the promoter-proximal regions of psaEF and psaABC in order to repress and stimulate their transcription, respectively. The translation/transcription start sites, Shine-Dalgarno sequences (ribosomal binding site), core promoter -10 and -35 elements, PhoP and RovA sites and PhoP/RovA consensus-like sequences were identified to determine the structural organization of PhoP/RovA-dependent promoters of psaEF and psaABC. Conclusion: RovA stimulated psaEF and psaABC, while PhoP repressed these two operons involving the direct association between RovA/PhoP and target promoter regions. The reciprocal regulation of psa genes by PhoP and RovA could contribute to the tightly controlled expression of the pH 6 antigen during infection.
Future Microbiology 02/2013; 8:271-80. · 3.82 Impact Factor
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ABSTRACT: Type III secretion system (T3SS) of the plague bacterium Y. pestis encodes a syringe-like structure consisting of more than 20 proteins, which can inject virulence effectors into host cells to modulate the cellular functions. Here in this report, interactions among the possible components in T3SS of Yersinia pestis were identified using yeast mating technique. A total of 57 genes, including all the pCD1-encoded genes except those involved in plasmid replication and partition, pseudogenes, and the putative transposase genes, were subjected to yeast mating analysis. 21 pairs of interaction proteins were identified, among which 9 pairs had been previously reported and 12 novel pairs were identified in this study. Six of them were tested by GST pull down assay, and interaction pairs of YscG-SycD, YscG-TyeA, YscI-YscF, and YopN-YpCD1.09c were successfully validated, suggesting that these interactions might play potential roles in function of Yersinia T3SS. Several potential new interactions among T3SS components could help to understand the assembly and regulation of Yersinia T3SS.
PLoS ONE 01/2013; 8(1):e54121. · 4.09 Impact Factor
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Yujun Cui,
Chang Yu,
Yanfeng Yan,
Dongfang Li,
Yanjun Li,
Thibaut Jombart,
Lucy A Weinert,
Zuyun Wang, Zhaobiao Guo,
Lizhi Xu, [......],
Jing Wang,
Shusen Yao,
Alexander Rakin,
Yingrui Li,
Daniel Falush,
Francois Balloux,
Mark Achtman,
Yajun Song,
Jun Wang,
Ruifu Yang
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ABSTRACT: The genetic diversity of Yersinia pestis, the etiologic agent of plague, is extremely limited because of its recent origin coupled with a slow clock rate. Here we identified 2,326 SNPs from 133 genomes of Y. pestis strains that were isolated in China and elsewhere. These SNPs define the genealogy of Y. pestis since its most recent common ancestor. All but 28 of these SNPs represented mutations that happened only once within the genealogy, and they were distributed essentially at random among individual genes. Only seven genes contained a significant excess of nonsynonymous SNP, suggesting that the fixation of SNPs mainly arises via neutral processes, such as genetic drift, rather than Darwinian selection. However, the rate of fixation varies dramatically over the genealogy: the number of SNPs accumulated by different lineages was highly variable and the genealogy contains multiple polytomies, one of which resulted in four branches near the time of the Black Death. We suggest that demographic changes can affect the speed of evolution in epidemic pathogens even in the absence of natural selection, and hypothesize that neutral SNPs are fixed rapidly during intermittent epidemics and outbreaks.
Proceedings of the National Academy of Sciences 12/2012; · 9.68 Impact Factor
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ABSTRACT: Yersinia pestis, the causative agent of plague, is proved to be a recently emerged clone from Y. pseudotuberculosis. However, the diseases they cause and their patterns of transmission are very different. People always focus on the genetic changes between Y. pestis and Y. pseudotuberculosis to reveal their pathogenic differences, and little is known about host defense differences to these two yersiniae. In this study, the effects of Y. pestis and Y. pseudotuberculosis on macrophages were analyzed. Cell apoptosis showed significant difference after macrophages infected by these two strains, and caspase-3 activity also demonstrated a similar tendency. Further, macrophage function activities were evaluated. We found during the early infection of Y. pestis, several basic functions of macrophages, including phagocytosis, secretion of cytokine TNF-α and nitric oxide (NO), macrophage polarity and antigen presenting, were significantly interrupted. In comparison, Y. pseudotuberculosis infection showed lower inhibition on macrophages. Especially, Y. pestis infection might cause macrophage to polarize to M2 macrophages in the early phase, compared with Y. pseudotuberculosis infection, which was different from the common acute infection. These results clearly indicated even in the early stage of infection, different host macrophage defense patterns could help us to understand the obvious virulence differences between Y. pestis and Y. pseudotuberculosis.
Scandinavian Journal of Immunology 08/2012; · 2.23 Impact Factor
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ABSTRACT: An acidic environment is frequently found in phagocytes, while the intracellular survival and growth of Streptococcus suis serotype 2 (S. suis S2) in phagocytes is an essential part of the infection cycle of this pathogen. In this study, we used DNA microarrays to
analyze the gene expression profile of S. suis S2 in response to acidic treatment. A total of 196 genes were differentially regulated when S. suis S2 was grown at pH5.8 relative to at pH7.2, especially including the inducible transcription of genes that encoded two-component
regulatory systems, protection and repair functions, and intracellular pH homeostasis. The data showed that S. suis S2 is capable of employing diverse responsive mechanisms to protect against or adapt to acidic stress.
Keywords
Streptococcus suis serotype 2–Expression profile–Acid stress–Microarray
Annals of Microbiology 04/2012; 61(3):505-510. · 0.69 Impact Factor
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ABSTRACT: Vibrio parahaemolyticus is a leading cause of infectious diarrhea and enterogastritis via the fecal-oral route. V. harveyi is a pathogen of fishes and invertebrates, and has been used as a model for quorum sensing (QS) studies. LuxR is the master QS regulator (MQSR) of V. harveyi, and LuxR-dependent expression of its own gene, qrr2-4 and aphA have been established in V. harveyi. Molecular regulation of target genes by the V. parahaemolyticus MQSR OpaR is still poorly understood.
The bioinformatics analysis indicated that V. parahaemolyticus OpaR, V. harveyi LuxR, V. vulnificu SmcR, and V. alginolyticus ValR were extremely conserved, and that these four MQSRs appeared to recognize the same conserved cis-acting signals, which was represented by the consensus constructs manifesting as a position frequency matrix and as a 20 bp box, within their target promoters. The MQSR box-like sequences were found within the upstream DNA regions of opaR, qrr2-4 and aphA in V. parahaemolyticus, and the direct transcriptional regulation of these target genes by OpaR were further confirmed by multiple biochemical experiments including primer extension assay, gel mobility shift assay, and DNase I footprinting analysis. Translation and transcription starts, core promoter elements for sigma factor recognition, Shine-Dalgarno sequences for ribosome recognition, and OpaR-binding sites were determined for the five target genes of OpaR, which gave a structural map of the OpaR-dependent promoters. Further computational promoter analysis indicated the above regulatory circuits were shared by several other closely related Vibrios but with slight exceptions.
This study gave a comprehensive computational and characterization of the direct transcriptional regulation of five target genes, opaR, qrr2-4 and ahpA, by OpaR in V. parahaemolyticus. These characterized regulatory circuits were conserved in V. harveyi and V. parahaemolyticus.
PLoS ONE 01/2012; 7(4):e34622. · 4.09 Impact Factor
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ABSTRACT: AphA is the master quorum-sensing (QS) regulator operating at low cell density in vibrios. Molecular regulation of target genes by AphA has been characterized in Vibrio harveyi and V. cholerae, but it is still poorly understood in V. parahaemolyticus.
The AphA proteins are extremely conserved in V. parahaemolyticus, Vibrio sp. Ex25, Vibrio sp. EJY3, V. harveyi, V. vulnificus, V. splendidus, V. anguillarum, V. cholerae, and V. furnissii. The above nine AphA orthologs appear to recognize conserved cis-acting DNA signals which can be represented by two consensus constructs, a 20 bp box sequence and a position frequency matrix. V. parahaemolyticus AphA represses the transcription of ahpA, qrr4, and opaR through direct AphA-target promoter DNA association, while it inhibits the qrr2-3 transcription in an indirect manner. Translation and transcription starts, core promoter elements for sigma factor recognition, Shine-Dalgarno sequences for ribosome recognition, and AphA-binding sites (containing corresponding AphA box-like sequences) were determined for the three direct AphA targets ahpA, qrr4, and opaR in V. parahaemolyticus.
AphA-mediated repression of ahpA, qrr2-4, and opaR was characterized in V. parahaemolyticus by using multiple biochemical and molecular experiments. The computational promoter analysis indicated the conserved mechanism of transcriptional regulation of QS regulator-encoding genes ahpA, qrr4, and opaR in vibrios.
PLoS ONE 01/2012; 7(9):e44210. · 4.09 Impact Factor
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ABSTRACT: Yersinia pestis synthesizes the attached biofilms in the flea proventriculus, which is important for the transmission of this pathogen by fleas. The hmsHFRS operons is responsible for the synthesis of exopolysaccharide (the major component of biofilm matrix), which is activated by the signaling molecule 3', 5'-cyclic diguanylic acid (c-di-GMP) synthesized by the only two diguanylate cyclases HmsT, and YPO0449 (located in a putative operonYPO0450-0448).
The phenotypic assays indicated that the transcriptional regulator Fur inhibited the Y. pestis biofilm production in vitro and on nematode. Two distinct Fur box-like sequences were predicted within the promoter-proximal region of hmsT, suggesting that hmsT might be a direct Fur target. The subsequent primer extension, LacZ fusion, electrophoretic mobility shift, and DNase I footprinting assays disclosed that Fur specifically bound to the hmsT promoter-proximal region for repressing the hmsT transcription. In contrast, Fur had no regulatory effect on hmsHFRS and YPO0450-0448 at the transcriptional level. The detection of intracellular c-di-GMP levels revealed that Fur inhibited the c-di-GMP production.
Y. pestis Fur inhibits the c-di-GMP production through directly repressing the transcription of hmsT, and thus it acts as a repressor of biofilm formation. Since the relevant genetic contents for fur, hmsT, hmsHFRS, and YPO0450-0448 are extremely conserved between Y. pestis and typical Y. pseudotuberculosis, the above regulatory mechanisms can be applied to Y. pseudotuberculosis.
PLoS ONE 01/2012; 7(12):e52392. · 4.09 Impact Factor
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ABSTRACT: Plague is one of the most dangerous diseases and is caused by Yersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n = 65) recovered from Y. pestis infection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r = 0.821; P < 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively, in vitro to the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines against Y. pestis infection and the development of new target-based diagnostics.
Clinical and vaccine immunology: CVI 12/2011; 19(2):228-34. · 2.37 Impact Factor
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ABSTRACT: A total of 18 variably-presented gene clusters (LVPCs) and nine previously characterized variable-number tandem repeats (VNTRs), and all known virulence markers were screened for their frequency and/or copy number in 251 global strains of Vibrio parahaemolyticus using PCR and gel or capillary electrophoresis. A two-step genotyping approach combining the use of LVPCs and VNTRs was established accordingly. The frequency profiles of LVPCs and virulence markers were primarily used to group the strains into six distinct complexes with different potential pathogenicity natures. The strains from each of these complexes were further analyzed with VNTRs to give a much more detailed discrimination of the strains. A genetic fingerprint-like database of a large collection of strains established with this two-stage approach would be very useful for identification, genotyping, origin tracing, and risk estimation of V. parahaemolyticus.
International journal of food microbiology 09/2011; 149(2):143-51. · 3.01 Impact Factor
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Huiying Yang,
Yuehua Ke,
Jian Wang,
Yafang Tan,
Sebenzile K Myeni,
Dong Li,
Qinghai Shi,
Yanfeng Yan,
Hui Chen, Zhaobiao Guo,
Yanzhi Yuan,
Xiaoming Yang,
Ruifu Yang,
Zongmin Du
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ABSTRACT: A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.
Infection and immunity 09/2011; 79(11):4413-24. · 4.21 Impact Factor
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ABSTRACT: A regulatory circuit composed of three porins (OmpF, OmpC, and OmpX) and two transcriptional regulators (OmpR and CRP) has previously been characterized in Yersinia pestis . In this follow-up study, OmpF2, an OmpF paralogue, was integrated into this regulatory circuit. Only basal expression was detected for ompF2 in the wild-type strain under different osmotic conditions. The ompF2 transcription was dramatically enhanced with increasing medium osmolarity in the ompR null mutant background. The CRP regulator had no regulatory effect on ompF2 under the growth conditions tested.
Canadian Journal of Microbiology 06/2011; 57(6):468-75. · 1.36 Impact Factor
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ABSTRACT: The regulator protein H-NS of Yersinia pestis was expressed using the Escherichia coli BL21lambdaDE3 protein expression system, and its DNA-binding activity was characterized.
The entire coding region of the hns gene was amplified by PCR from Y. pestis strain 201, and then cloned into the BamHI and Sal sites of the vector pET28a. The recombinant plasmid pET28a-hns was transformed into BL21lambdaDE3. Over-expression of His-H-NS in the LB medium was induced by addition of 1 mM IPTG (isopropyl-b-D-thiogalactoside). The over-expressed protein was purified under native conditions with nickel loaded HiTrap Chelating Sepharose columns (Amersham). The electrophoretic mobility shift assay and DNase I footprinting experiments were carried out to analyze the DNA-binding activity of His-H-NS in vitro.
The purified His-H-NS protein could bind to the upstream DNA regions of psaA, psaE and rovA of Y. pestis, and the H-NS-binding sites were determined at the single nucleotide resolution.
The purified His-H-NS protein could bind to target DNA fragments, suggesting that H-NS would regulate the transcription of relevant genes in Y. pests.
ACTA MICROBIOLOGICA SINICA 05/2011; 51(5):615-21.
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Bei Li,
Yafang Tan,
Jingyu Guo,
Baizhong Cui,
Zuyun Wang,
Hu Wang,
Lei Zhou, Zhaobiao Guo,
Ziwen Zhu,
Zongmin Du,
Ruifu Yang
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ABSTRACT: Yersinia pestis is a bacterium that is transmitted between fleas, which have a body temperature of 26 °C, and mammalian hosts, which have a body temperature of 37 °C. To adapt to the temperature shift, phenotype variations, including virulence, occur. In this study, an antigen microarray including 218 proteins of Y. pestis was used to evaluate antibody responses in a pooled plague serum that was unadsorbed, adsorbed by Y. pestis cultivated at 26 °C, or adsorbed by Y. pestis cultivated at 26 and 37 °C to identify protein expression changes during the temperature shift. We identified 12 proteins as being expressed at 37 °C but not at 26 °C, or expressed at significantly higher levels at 37 °C than at 26 °C. The antibodies against 7 proteins in the serum adsorbed by Y. pestis cultivated at 26 and 37 °C remained positive, suggesting that they were not expressed on the surface of Y. pestis in LB broth in vitro or specifically expressed in vivo. This study proved that protein microarray and antibody profiling comprise a promising technique for monitoring gene expression at the protein level and for better understanding pathogenicity, to find new vaccine targets against plague.
Canadian Journal of Microbiology 04/2011; 57(4):287-94. · 1.36 Impact Factor
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ABSTRACT: Streptococcus suis serotype 2 (S. suis S2) is able to cause human infections ranging from superficial wounded skin infections to severe invasive infections such as meningitis and streptococcal toxic shock-like syndrome. During its infection cycle, S. suis S2 must acclimatize itself to temperature shift. Herein, a whole-genome DNA microarray was used to investigate the global transcriptional regulation of an invasive strain of S. suis S2 grown to late-exponential phase at 29°C or 40°C relative to 37°C. The differentially regulated genes that were detected included those encoding virulence factors, antigenic proteins, ATP-binding-cassette transporters, and proteins of unknown functions. Our data provided a global profile of gene transcription induced by temperature alteration and shed light on some unforeseen lines for further pathogenesis investigation.
Vector borne and zoonotic diseases (Larchmont, N.Y.) 03/2011; 11(3):215-21. · 2.61 Impact Factor
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ABSTRACT: The osmotic regulator OmpR in Escherichia coli regulates differentially the expression of major porin proteins OmpF and OmpC. In Yersinia enterocolitica and Y. pseudotuberculosis, OmpR is required for both virulence and survival within macrophages. However, the phenotypic and regulatory roles of OmpR in Y. pestis are not yet fully understood.
Y. pestis OmpR is involved in building resistance against phagocytosis and controls the adaptation to various stressful conditions met in macrophages. The ompR mutation likely did not affect the virulence of Y. pestis strain 201 that was a human-avirulent enzootic strain. The microarray-based comparative transcriptome analysis disclosed a set of 224 genes whose expressions were affected by the ompR mutation, indicating the global regulatory role of OmpR in Y. pestis. Real-time RT-PCR or lacZ fusion reporter assay further validated 16 OmpR-dependent genes, for which OmpR consensus-like sequences were found within their upstream DNA regions. ompC, F, X, and R were up-regulated dramatically with the increase of medium osmolarity, which was mediated by OmpR occupying the target promoter regions in a tandem manner.
OmpR contributes to the resistance against phagocytosis or survival within macrophages, which is conserved in the pathogenic yersiniae. Y. pestis OmpR regulates ompC, F, X, and R directly through OmpR-promoter DNA association. There is an inducible expressions of the pore-forming proteins OmpF, C, and × at high osmolarity in Y. pestis, in contrast to the reciprocal regulation of them in E. coli. The main difference is that ompF expression is not repressed at high osmolarity in Y. pestis, which is likely due to the absence of a promoter-distal OmpR-binding site for ompF.
BMC Microbiology 02/2011; 11:39. · 3.04 Impact Factor
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ABSTRACT: The cAMP receptor protein (CRP) is a global bacterial regulator that controls many target genes. The CRP-cAMP complex regulates the ompR-envZ operon in E. coli directly, involving both positive and negative regulations of multiple target promoters; further, it controls the production of porins indirectly through its direct action on ompR-envZ. Auto-regulation of CRP has also been established in E. coli. However, the regulation of porin genes and its own gene by CRP remains unclear in Y. pestis.
Y. pestis employs a distinct mechanism indicating that CRP has no regulatory effect on the ompR-envZ operon; however, it stimulates ompC and ompF directly, while repressing ompX. No transcriptional regulatory association between CRP and its own gene can be detected in Y. pestis, which is also in contrast to the fact that CRP acts as both repressor and activator for its own gene in E. coli. It is likely that Y. pestis OmpR and CRP respectively sense different signals (medium osmolarity, and cellular cAMP levels) to regulate porin genes independently.
Although the CRP of Y. pestis shows a very high homology to that of E. coli, and the consensus DNA sequence recognized by CRP is shared by the two bacteria, the Y. pestis CRP can recognize the promoters of ompC, F, and X directly rather than that of its own gene, which is different from the relevant regulatory circuit of E. coli. Data presented here indicate a remarkable remodeling of the CRP-mediated regulation of porin genes and of its own one between these two bacteria.
BMC Microbiology 02/2011; 11:40. · 3.04 Impact Factor
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ABSTRACT: The serum levels of interleukin-2 (IL-2), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-4, IL-6, and IL-10 of pneumonic plague patients were determined by enzyme-linked immunosorbent assay. IL-6 was the only elevated cytokine in the patients, and its level increased with a clear time course, indicating that IL-6 might be a prognostic marker for predicting the progression of plague.
Clinical and vaccine immunology: CVI 01/2011; 18(1):184-6. · 2.37 Impact Factor
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ABSTRACT: A collection of 174 global isolates of Vibrio parahaemolyticus were analyzed by multilocus sequence typing (MLST) on the basis of ten conserved genes. The results showed a high level of nucleotide and allelic diversity with the evidence of purifying selection and of frequent recombination. Recombination played a much greater role than mutation in generating genetic heterogeneity. The 174 strains could be assigned into 89 different sequence types, which could be further separated into six clonal complexes (CCs; CC1 to CC6) plus 71 singletons. The three major CCs, namely CC1 to CC3, corresponded to the groups of pre-1996 clinical old-O3:K6 strains (trh(+), T3SS2β(+), tdh(-), T3SS2α(-), and GS-PCR(-)), post-1996 pandemic strains (trh(-), T3SS2β(-), tdh(+), T3SS2α(+), and GS-PCR(+)) and non-clinical isolates (trh(-), T3SS2β(-), tdh(-), T3SS2α(-), and GS-PCR(-)), respectively. The MLST data enable the construction of a phylogenetic structure from the allelic profiles rather the nucleotide sequences, so as to reduce the affect of frequent recombination. The six CCs arose on a background of mutation and recombination, and according to the previously reported data, this bacterium could be evolved fast due to lateral acquisition of foreign genes especially including those encoding virulence determinants. V. parahaemolyticus had a typical epidemic population structure that is driven by mutation, recombination and lateral gene transfer.
International journal of food microbiology 01/2011; 145(1):106-12. · 3.01 Impact Factor
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Hu Wang,
Yujun Cui,
Zuyun Wang,
Xiaoyi Wang, Zhaobiao Guo,
Yanfeng Yan,
Chao Li,
Baizhong Cui,
Xiao Xiao,
Yonghai Yang,
Zhizhen Qi,
Guojun Wang,
Baiqing Wei,
Shouhong Yu,
Duolong He,
Hongjian Chen,
Gang Chen,
Yajun Song,
Ruifu Yang
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ABSTRACT: Primary pneumonic plague (PPP) caused by Yersinia pestis is the most threatening clinical form of plague. An outbreak was reported in July 2009 in Qinghai Province, China.
This outbreak was investigated by clinical, epidemiological, bacteriological, and immunological methods. Multilocus variable number tandem repeat analysis (MLVA) was used to track the source of the outbreak.
The index case, a patient with PPP, contaminated 11 close contacts. All the 12 cases, including the index patient, experienced sudden onset of fever, headache, and productive coughing with bloody sputum. Three of them died. Nevertheless, another 61 direct and 256 indirect contacts were not infected during the 2-week quarantine. Antibodies to F1 antigen were detected in 9 survival cases, with a 4-fold increase in titers in serum samples collected at different periods. Seven strains of Y. pestis were isolated from dogs and patients. Field investigation and MLVA of the isolated strains revealed that this outbreak was started by a deceased dog.
Dogs are believed to be an indicator animal for plague surveillance, but their association with PPP is rare. Our results provide evidence for this possibility, which suggests the public health significance of dogs as a source of plague.
Clinical Infectious Diseases 01/2011; 52(2):185-90. · 9.15 Impact Factor