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Comparative Genomic Hybridization Identifies Virulence Differences in Streptococcus suis  [PDF]
Han Zheng, Ruiting Lan, Xiao Zheng, Zhigang Cui, Zhijie Liu, Xuemei Bai, Shaobo Ji, Marcelo Gottschalk, Jianguo Xu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087866
Abstract: Streptococcus suis is an important zoonotic pathogen. However, identification of virulent S. suis strains is complicated because of the high diversity of the species. Here we evaluated the genetic difference among S. suis strains using comparative genomic hybridization (CGH) and virulence variation in vivo and in vitro. We showed that different clades differed in their ability to activate TLR2/6 in vitro and their capacity to induce cytokine production in vivo as well as their resistance to phagocytosis and survival in vivo. Our data showed the S. suis strains tested can be classified into three groups having differing levels of virulence: epidemic and highly virulent strains were clustered into clade Ia (epidemic and highly virulent group, E/HV group), virulent strains were clustered into clade Ib (virulent group, V group), and intermediately or weakly virulent strains were clustered into other clades (intermediately or weakly virulent group, I/WV group). Our study provided further insight into the genomic and virulence variation of S. suis.
Rapid Evolution of Virulence and Drug Resistance in the Emerging Zoonotic Pathogen Streptococcus suis  [PDF]
Matthew T. G. Holden, Heidi Hauser, Mandy Sanders, Thi Hoa Ngo, Inna Cherevach, Ann Cronin, Ian Goodhead, Karen Mungall, Michael A. Quail, Claire Price, Ester Rabbinowitsch, Sarah Sharp, Nicholas J. Croucher, Tran Bich Chieu, Nguyen Thi Hoang Mai, To Song Diep, Nguyen Tran Chinh, Michael Kehoe, James A. Leigh, Philip N. Ward, Christopher G. Dowson, Adrian M. Whatmore, Neil Chanter, Pernille Iversen, Marcelo Gottschalk, Josh D. Slater, Hilde E. Smith, Brian G. Spratt, Jianguo Xu, Changyun Ye, Stephen Bentley, Barclay G. Barrell, Constance Schultsz, Duncan J. Maskell, Julian Parkhill
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006072
Abstract: Background Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. Methodology/Principal Findings The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, ~40% of the ~2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three ~90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. Conclusions/Significance The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.
Relationship Between Fluoroquinolone Resistance and gyrA, parC Gene in Streptococcus suis Type 2 Isolates in Hebei Province China
Ping Rui,Zengjun Ma,QiuYue Wang,Hai Fang,JianHua Wu,ZhiXin Fu,Qing Hui Jia,Xuexia Wen
Journal of Animal and Veterinary Advances , 2012, DOI: 10.3923/javaa.2012.719.722
Abstract: To detect the relationship between fluoroquinolone resistance and gyrA, parC gene mutation in Streptococcus suis type 2. The MIC of 14 strains of Streptococcus suis type 2 were determined by microdilution. The genes encoding the Quinolone-Resistance Determining Region (QRDRs) of parC and gyrA in fluoroquinolone-susceptible and resistant Streptococcus suis clinical isolates were identified and sequenced. Ser to Phe and Arg to Leu mutation at position 79 and 87 of the parC gene was detected in fluoroquinolone resistance SS2 and Arg to Ser or Ser to Arg mutations at the position 66 or 81 of gyrA gene were detected in 2 highly resistance strains; no amino acid changes in gyrA or parC were detected for 7 fluoroquinolone-susceptible strains; the mutations in both genes were found in the strains with MIC of fluoroquinolone >32 μg mL-1. Mutations in parC gene may result in low level resistance against fluoroquinolone and mutations in both gyrA and parC genes result in high level resistance.
Detection of the Major Macrolide Resistance Genes in Streptococcus suis Serotype 2 Isolates in Hebei Province China
Ping Rui,PeiGuo Li,Zengjun Ma,QinYe Song,CaiRan Yang,Ping Shen,SuMin Pan,Yufang Guo
Journal of Animal and Veterinary Advances , 2012, DOI: 10.3923/javaa.2012.781.784
Abstract: To investigate the distribution of ermB, ermA and mefA related to the erythromycin resistance gene, 32 drug-resistant Streptococcus suis type 2 isolates from different areas in Hebei province were studied to detect the ermB, ermA and mefA genes by PCR amplification. The results showed that among the drug-resistant 32 strains, 100% (32/32) amplified ermB gene, 21.88% (7/32) isolates contained ermA gene and none of these strains was positive for mefA gene. The researchers concluded that erythromycin resistance mechanism of pig Streptococcus isolates is mainly mediated by ermB gene. Nucleotide sequences comparison showed that the ermB gene of 20 strains and the nucleotide sequences in the GenBank had the sequence similarity of 95-100%. Compared with the reference sequence of AJ972604.1, Ser to Asn mutation at position 100 and Arg to His mutation at position 118 of ermB was mainly detected in the 20 strains. The researchers concluded that the ermB gene is relatively stable.
Comparative analysis of whole genome structure of Streptococcus suis using whole genome PCR scanning
ZhaoHui Xiong,CanDong Wei,Jian Yang,JunPing Peng,XingYe Xu,Yu Wang,Qi Jin
Science China Life Sciences , 2008, DOI: 10.1007/s11427-008-0003-2
Abstract: An outbreak associated with Streptococcus suis infection in humans emerged in Sichuan province, China in 2005. The outbreak is atypical for the apparent large number of human cases, high fatality rate and geographical spread. To determine whether the bacterium has changed, we compared both human and animal isolates from the Sichuan outbreak with those collected previously within China and in other countries using whole genome PCR scanning (WGPScaning) comparative sequencing of several known virulence factor genes and multilocus sequence typing (MLST) analysis. WGPScanning analysis showed that all primer pairs yielded PCR products of the expected sizes in all four strains tested. The nucleotide sequences of all the detected virulence factor genes are identical in the four strains and MLST results showed that the four isolates studied and reference strain all belonged to the ST1 complex. No new genetic changes were found in the genome structure of the isolates from this Sichuan outbreak.
Probing genomic diversity and evolution of Streptococcus suis serotype 2 by NimbleGen tiling arrays
Zuowei Wu, Ming Li, Changjun Wang, Jing Li, Na Lu, Ruifen Zhang, Yongqiang Jiang, Ruifu Yang, Cuihua Liu, Hui Liao, George F Gao, Jiaqi Tang, Baoli Zhu
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-219
Abstract: 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.Streptococcus suis serotype 2 (S. suis 2, SS2) is an important zoonotic pathogen that causes severe porcine infectious diseases, including arthritis, meningitis, and pneumonia [1-3]. Virulent strains of SS2 can also be transmitted to humans (especially abattoir workers and pork handlers) by direct contact, causing meningitis, permanent hearing loss, septic shock, and even death. Two large-scale outbreaks of severe SS2 epidemics occurred in China in 1998 and 2005, causing great economic losses in the swine industry. These two outbreaks also posed serious public health risks from the newly emerging streptococcal toxin shock syndrome (STSS), which claimed 52 lives [4]. Over the past decade, considerable attention has been given to the study of virulence factors (e.g., CPS, MRP, EF, and suilysin) and the pathogen-host interaction in this emerging pathogen. However, comparative studies at the wh
A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates  [PDF]
Chen Chen, Jiaqi Tang, Wei Dong, Changjun Wang, Youjun Feng, Jing Wang, Feng Zheng, Xiuzhen Pan, Di Liu, Ming Li, Yajun Song, Xinxing Zhu, Haibo Sun, Tao Feng, Zhaobiao Guo, Aiping Ju, Junchao Ge, Yaqing Dong, Wen Sun, Yongqiang Jiang, Jun Wang, Jinghua Yan, Huanming Yang, Xiaoning Wang, George F. Gao, Ruifu Yang, Jian Wang, Jun Yu
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000315
Abstract: 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.
Lysozyme Resistance in Streptococcus suis Is Highly Variable and Multifactorial  [PDF]
Paul J. Wichgers Schreur, Christian van Weeghel, Johanna M. J. Rebel, Mari A. Smits, Jos P. M. van Putten, Hilde E. Smith
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036281
Abstract: Background Streptococcus suis is an important infectious agent for pigs and occasionally for humans. The host innate immune system plays a key role in preventing and eliminating S. suis infections. One important constituent of the innate immune system is the protein lysozyme, which is present in a variety of body fluids and immune cells. Lysozyme acts as a peptidoglycan degrading enzyme causing bacterial lysis. Several pathogens have developed mechanisms to evade lysozyme-mediated killing. In the present study we compared the lysozyme sensitivity of various S. suis isolates and investigated the molecular basis of lysozyme resistance for this pathogen. Results The lysozyme minimal inhibitory concentrations of a wide panel of S. suis isolates varied between 0.3 to 10 mg/ml. By inactivating the oatA gene in a serotype 2 and a serotype 9 strain, we showed that OatA-mediated peptidoglycan modification partly contributes to lysozyme resistance. Furthermore, inactivation of the murMN operon provided evidence that additional peptidoglycan crosslinking is not involved in lysozyme resistance in S. suis. Besides a targeted approach, we also used an unbiased approach for identifying factors involved in lysozyme resistance. Based on whole genome comparisons of a lysozyme sensitive strain and selected lysozyme resistant derivatives, we detected several single nucleotide polymorphisms (SNPs) that were correlated with the lysozyme resistance trait. Two SNPs caused defects in protein expression of an autolysin and a capsule sugar transferase. Analysis of specific isogenic mutants, confirmed the involvement of autolysin activity and capsule structures in lysozyme resistance of S. suis. Conclusions This study shows that lysozyme resistance levels are highly variable among S. suis isolates and serotypes. Furthermore, the results show that lysozyme resistance in S. suis can involve different mechanisms including OatA-mediated peptidolycan modification, autolysin activity and capsule production.
Acute meningitis by Streptococcus suis
Maria-Jesus Corrales-Arroyo,Maria Angeles Del Real-Francia,Amalia Hernandez-Gonzalez,Jose Manuel Morales Puebla
Journal of Microbiology and Infectious Diseases , 2012,
Abstract: Streptococcus suis is a coccus Gram positive, anaerobic optional. Human infection by this microorganism is a zoonoticdisease that usually presents as purulent meningitis. Mortality is low but is common sequelae. A case of meningitis byS. suis secondary to contact with pigs is presented here. A 35-year-old male patient was admitted to the hospital complainingof high fever, malaise, vomiting and headache. A physical examination revealed decreased level of consciousness,with adequate response to painful stimulus and his eyes with deconjugated gaze. S. suis was isolated in bloodculture. He was treated with cefotaxime, vancomycin and acyclovir in the intensive care unit. He experienced progressiveimprovement. He was discharged with severe deafness and a minimally unstable gait as sequellae. J Microbiol Infect Dis2012; 2(4): 160-162Key words: Streptococcus suis, meningitis, deafness.
Meningitis por Streptococcus suis
Geffner Sclarsky,D. E.; Moreno Mu?oz,R.; Campillo Alpera,Ma.S.; Pardo Serrano,F.J.; Gómez Gómez,A.; Martínez-Lozano,Ma.D.;
Anales de Medicina Interna , 2001, DOI: 10.4321/S0212-71992001000600007
Abstract: human infection by streptococcus suis (s. suis) is a zoonosis, with a known occupational risk and clinical presentation mainly as a purulent meningitis with low mortality and frequent hearing loss and ataxia sequela. less than 150 human cases have been reported since original one thirty years ago. there is a geographical distribution most patients living in northen europe and south asia. s. suis disease in human has been reported in two patients in spain the last years. we present two patients with s. suis meningitis, both were men with occupation related by pork meet, and good outcome. they come at our hospital in a lapse of one month. both had neurosensorial hearing loss and walking ataxia. one patient had peripheral facial paralysis and diplopia because of paresia of contralateral sixth nerve, with complete resolution at three months.the rare presentation of s. suis meningitis in our country must not forget us to record the working risk at anamnesis.
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