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[PMID]: 29458554 [Au] Autor: Osaka S; Okuzumi K; Koide S; Tamai K; Sato T; Tanimoto K; Tomita H; Suzuki M; Nagano Y; Shibayama K; Arakawa Y; Nagano N [Ad] Endereço: 1​Department of Health and Medical Sciences, Shinshu University Graduate School of Medicine, Nagano, Japan. [Ti] Título: Genetic shifts in methicillin-resistant Staphylococcus aureus epidemic clones and toxin gene profiles in Japan: comparative analysis among pre-epidemic, epidemic and post-epidemic phases. [So] Source: J Med Microbiol;67(3):392-399, 2018 Mar. [Is] ISSN: 1473-5644 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: PURPOSE: The decline in methicillin-resistant Staphylococcus aureus (MRSA) isolation rates has become a general observation worldwide, including Japan. We hypothesized that some genetic shift in MRSA might cause this phenomenon, and therefore we investigated the genetic profiles among MRSA clinical isolates obtained from three different epidemic phases in Japan. METHODOLOGY: A total of 353 MRSA isolates were selected from 202 medical facilities in 1990 (pre-epidemic phase), 2004 (epidemic phase) and 2016 (post-epidemic phase). Molecular typing was performed by PCR detection of 22 genes using the polymerase chain reaction (PCR)-based ORF typing (POT) system, including an additional eight genes including small genomic islets and seven toxin genes. RESULTS: Isolates with a POT1 of score 93, identified as presumed clonal complex (pCC)5-staphylococcal cassette chromosome mec (SCCmec) type II including ST5-SCCmec type II New York/Japan clone, represented the major epidemic MRSA lineage in 1990 and 2004. In 2016, however, a marked decrease in isolates with a POT1 score of 93, along with changes in the epidemiology of toxin genes carried, was noted, where the carriers of tst genes including the tst-sec combination were markedly reduced, and those possessing the seb gene alone were markedly increased. Rather, isolates with a POT1 score of 106, including pCC1 or pCC8 among the isolates with SCCmec type IV, which often links to community-associated MRSA, were predominant. Interestingly, the pCC1 and pCC8 lineages were related to sea and tst-sec carriage, respectively. CONCLUSIONS: Over time, a transition in MRSA genetic profiles from a POT1 score of 93 in 1990 and 2004 to 106 in 2014 was found in Japan. [Mh] Termos MeSH primário: Toxinas Bacterianas/genética Epidemias Deriva Genética Staphylococcus aureus Resistente à Meticilina/genética Infecções Estafilocócicas/epidemiologia Infecções Estafilocócicas/microbiologia [Mh] Termos MeSH secundário: Antibacterianos/farmacologia Infecção Hospitalar/epidemiologia Exotoxinas/genética Seres Humanos Japão/epidemiologia Leucocidinas/genética Meticilina/farmacologia Resistência a Meticilina/genética Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos Staphylococcus aureus Resistente à Meticilina/isolamento & purificação Testes de Sensibilidade Microbiana Tipagem Molecular Fatores de Virulência/genética [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Bacterial Agents); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Leukocidins); 0 (Virulence Factors); Q91FH1328A (Methicillin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180221 [St] Status: MEDLINE [do] DOI: 10.1099/jmm.0.000687

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[PMID]: 28470625 [Au] Autor: Martínez-Hernández SL; Cervantes-García D; Muñoz-Ortega M; Aldaba-Muruato LR; Loera-Muro VM; Ascacio-Martínez JA; de Jesús Loera-Arias M; de Oca-Luna RM; Ventura-Juárez J [Ad] Endereço: Departamento de Morfología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad # 940, Ciudad Universitaria, C. P. 20131, Aguascalientes, AGS, Mexico. [Ti] Título: An anti-amoebic vaccine: generation of the recombinant antigen LC3 from Entamoeba histolytica linked to mutated exotoxin A (PEΔIII) via the Pichia pastoris system. [So] Source: Biotechnol Lett;39(8):1149-1157, 2017 Aug. [Is] ISSN: 1573-6776 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To generate an immunogenic chimeric protein containing the Entamoeba histolytica LC3 fragment fused to the retrograde delivery domains of exotoxin A of Pseudomonas aeruginosa and KDEL3 for use as an effective vaccine. RESULTS: A codon-optimized synthetic gene encoding the PEΔIII-LC3-KDEL3 fusion construct was designed for expression in Pichia pastoris. This transgene was subcloned into the plasmid pPIC9 for methanol-inducible expression. After transformation and selection of positive-transformed clones by PCR, the expression of the recombinant protein PEΔIII-LC3-KDEL3 was elicited. SDS-PAGE, protein glycosylation staining and western blot assays demonstrated a 67 kDa protein in the medium culture supernatant. The recombinant protein was detected with a polyclonal anti-6X His tag antibody and a polyclonal E. histolytica-specific antibody. A specific antibody response was induced in hamsters after immunization with this protein. CONCLUSIONS: We report for the first time the design and expression of the recombinant E. histolytica LC3 protein fused to PEΔIII and KDEL3, with potential application as an immunogen. [Mh] Termos MeSH primário: ADP Ribose Transferases/genética Toxinas Bacterianas/genética Entamoeba histolytica/genética Exotoxinas/genética Proteínas Recombinantes de Fusão/genética Vacinas Fatores de Virulência/genética [Mh] Termos MeSH secundário: ADP Ribose Transferases/imunologia Animais Toxinas Bacterianas/imunologia Entamoeba histolytica/imunologia Exotoxinas/imunologia Pichia/genética Proteínas Recombinantes de Fusão/imunologia Fatores de Virulência/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Recombinant Fusion Proteins); 0 (Vaccines); 0 (Virulence Factors); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.31 (toxA protein, Pseudomonas aeruginosa) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180202 [Lr] Data última revisão: 180202 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170505 [St] Status: MEDLINE [do] DOI: 10.1007/s10529-017-2341-2

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[PMID]: 29179212 [Au] Autor: Sun XX; Zhang SS; Dai CY; Peng J; Pan Q; Xu LF; Ma XL [Ad] Endereço: Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China. [Ti] Título: LukS-PV-Regulated MicroRNA-125a-3p Promotes THP-1 Macrophages Differentiation and Apoptosis by Down-Regulating NF1 and Bcl-2. [So] Source: Cell Physiol Biochem;44(3):1093-1105, 2017. [Is] ISSN: 1421-9778 [Cp] País de publicação: Switzerland [La] Idioma: eng [Ab] Resumo: BACKGROUND/AIMS: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We have previously demonstrated that LukS-PV potently promoted differentiation and induced apoptosis in THP-1 cells. However, the precise mechanisms of these actions remain unknown. MicroRNAs (miRs) play important roles in cellular differentiation and apoptosis. This study aimed to investigate the role of miR-125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying mechanism in THP-1 cells. METHODS: MicroRNA profiling analyses were conducted to determine differential miRNA expression levels in THP-1 cells treated with LukS-PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of-function and loss-of-function experiments. Bioinformatics analysis and luciferase reporter assays were used to confirm the targets of miR-125a-3p. The effects of the miR-125a-3p targets on cellular differentiation were determined by knocking them down. RESULTS: MiR-125a-3p was up-regulated after treating the human monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p positively regulated apoptosis and differentiation in THP-1 cells treated with LukS-PV. Concordantly, luciferase reporter assays confirmed that neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly promoted differentiation in vitro. Finally, the extracellular signal-regulated kinase (ERK) pathway, a downstream target of NF1, was activated after NF1 knockdown. CONCLUSIONS: These findings confirm that miR-125a-3p is involved in LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells. [Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos Toxinas Bacterianas/farmacologia Diferenciação Celular/efeitos dos fármacos Exotoxinas/farmacologia Leucocidinas/farmacologia MicroRNAs/metabolismo Neurofibromina 1/metabolismo Proteínas Proto-Oncogênicas c-bcl-2/metabolismo [Mh] Termos MeSH secundário: Regiões 3' não Traduzidas Antagomirs/metabolismo Toxinas Bacterianas/genética Toxinas Bacterianas/metabolismo Sequência de Bases Caspase 3/metabolismo Linhagem Celular Regulação para Baixo/efeitos dos fármacos Exotoxinas/genética Exotoxinas/metabolismo MAP Quinases Reguladas por Sinal Extracelular/metabolismo Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos Seres Humanos Leucocidinas/genética Leucocidinas/metabolismo Macrófagos/citologia Macrófagos/efeitos dos fármacos Macrófagos/metabolismo MicroRNAs/antagonistas & inibidores MicroRNAs/genética Neurofibromina 1/antagonistas & inibidores Neurofibromina 1/genética Fosforilação/efeitos dos fármacos Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores Proteínas Proto-Oncogênicas c-bcl-2/genética Proteínas Recombinantes/biossíntese Proteínas Recombinantes/isolamento & purificação Proteínas Recombinantes/farmacologia Alinhamento de Sequência Transdução de Sinais/efeitos dos fármacos Transcriptoma/efeitos dos fármacos Proteína X Associada a bcl-2/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (3' Untranslated Regions); 0 (Antagomirs); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Leukocidins); 0 (MIRN125 microRNA, human); 0 (MicroRNAs); 0 (Neurofibromin 1); 0 (Panton-Valentine leukocidin); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (Recombinant Proteins); 0 (bcl-2-Associated X Protein); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases); EC 3.4.22.- (Caspase 3) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180118 [Lr] Data última revisão: 180118 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171128 [St] Status: MEDLINE [do] DOI: 10.1159/000485415

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[PMID]: 29261764 [Au] Autor: Leistner R; Kola A; Gastmeier P; Krüger R; Hoppe PA; Schneider-Burrus S; Zuschneid I; Wischnewski N; Bender J; Layer F; Niebank M; Scheibenbogen C; Hanitsch LG [Ad] Endereço: Institute of Hygiene and Environmental Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany. [Ti] Título: Pyoderma outbreak among kindergarten families: Association with a Panton-Valentine leukocidin (PVL)-producing S. aureus strain. [So] Source: PLoS One;12(12):e0189961, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: OBJECTIVES: We report on an outbreak of skin and soft tissue infections (SSTI) among kindergarten families. We analyzed the transmission route and aimed to control the outbreak. METHODS: The transmission route was investigated by nasal screening for Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus (PVL-SA), subsequent microbiological investigation including whole genome sequencing and a questionnaire-based analysis of epidemiological information. The control measures included distribution of outbreak information to all individuals at risk and implementation of a Staphylococcus aureus decontamination protocol. RESULTS: Individuals from 7 of 19 families were either colonized or showed signs of SSTI such as massive abscesses or eye lid infections. We found 10 PVL-SA isolates in 9 individuals. In the WGS-analysis all isolates were found identical with a maximum of 17 allele difference. The clones were methicillin-susceptible but cotrimoxazole resistant. In comparison to PVL-SAs from an international strain collection, the outbreak clone showed close genetical relatedness to PVL-SAs from a non-European country. The questionnaire results showed frequent travels of one family to this area. The results also demonstrated likely transmission via direct contact between families. After initiation of Staphylococcus aureus decontamination no further case was detected. CONCLUSIONS: Our outbreak investigation showed the introduction of a PVL-SA strain into a kindergarten likely as a result of international travel and further transmission by direct contact. The implementation of a Staphylococcus aureus decontamination protocol was able to control the outbreak. [Mh] Termos MeSH primário: Toxinas Bacterianas/biossíntese Surtos de Doenças/estatística & dados numéricos Exotoxinas/biossíntese Leucocidinas/biossíntese Pioderma/epidemiologia Pioderma/microbiologia Infecções Estafilocócicas/epidemiologia Infecções Estafilocócicas/microbiologia Staphylococcus aureus/fisiologia [Mh] Termos MeSH secundário: Alelos Pré-Escolar Família Seres Humanos Funções Verossimilhança Filogenia Apoio Social [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Leukocidins); 0 (Panton-Valentine leukocidin) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180108 [Lr] Data última revisão: 180108 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171221 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0189961

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[PMID]: 29277757 [Au] Autor: Michalska M; Schultze-Seemann S; Kuckuck I; Wolf P [Ad] Endereço: Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. [Ti] Título: Evaluation of Humanized/De-immunized Anti-PSMA Immunotoxins for the Treatment of Prostate Cancer. [So] Source: Anticancer Res;38(1):61-69, 2018 01. [Is] ISSN: 1791-7530 [Cp] País de publicação: Greece [La] Idioma: eng [Ab] Resumo: BACKGROUND: We generated humanized/de-immunized immunotoxins targeting the prostate-specific membrane antigen (PSMA) and tested their cytotoxic activity against prostate cancer cells in vitro. MATERIALS AND METHODS: The humanized/de-immunized version of our murine anti-PSMA single-chain antibody fragment (scFv) D7, termed hD7-1(VL-VH), was ligated to the 40-kDa toxin domain of Pseudomonas aeruginosa exotoxin A (PE40), and to the deimmunized 24-kDa toxin domains PE24 or PE24mut. The immunotoxins designated as hD7-1(VL-VH)-PE40, hD7-1(VL-VH)-PE24 and hD7-1(VL-VH)-PE24mut were bacterially expressed and purified by affinity chromatography. Binding and cytotoxicity were examined by flow cytometry and viability assay, respectively. RESULTS: All immunotoxins revealed strong binding to prostate cancer cells expressing PSMA and specific cytotoxicity, with half-maximal inhibitory concentration values in the picomolar range. CONCLUSION: We successfully created powerful anti-PSMA immunotoxins with reduced immunogenicity for further clinical development and application against advanced prostate cancer. [Mh] Termos MeSH primário: Antígenos de Superfície/imunologia Glutamato Carboxipeptidase II/imunologia Imunotoxinas/farmacologia Neoplasias da Próstata/imunologia [Mh] Termos MeSH secundário: ADP Ribose Transferases/genética ADP Ribose Transferases/imunologia Animais Toxinas Bacterianas/genética Toxinas Bacterianas/imunologia Linhagem Celular Tumoral Escherichia coli/genética Exotoxinas/genética Exotoxinas/imunologia Seres Humanos Masculino Camundongos Neoplasias da Próstata/tratamento farmacológico Fatores de Virulência/genética Fatores de Virulência/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, Surface); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Immunotoxins); 0 (Virulence Factors); EC 2.4.2.- (ADP Ribose Transferases); EC 2.4.2.31 (toxA protein, Pseudomonas aeruginosa); EC 3.4.17.21 (Glutamate Carboxypeptidase II); EC 3.4.17.21 (glutamate carboxypeptidase II, human) [Em] Mês de entrada: 1801 [Cu] Atualização por classe: 180104 [Lr] Data última revisão: 180104 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171227 [St] Status: MEDLINE

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[PMID]: 28983018 [Au] Autor: Wayne AS; Shah NN; Bhojwani D; Silverman LB; Whitlock JA; Stetler-Stevenson M; Sun W; Liang M; Yang J; Kreitman RJ; Lanasa MC; Pastan I [Ad] Endereço: Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA. [Ti] Título: Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia. [So] Source: Blood;130(14):1620-1627, 2017 Oct 05. [Is] ISSN: 1528-0020 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter phase 1 study was conducted to determine the maximum-tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (N = 55). Moxetumomab pasudotox was administered as a 30-minute IV infusion at doses of 5 to 50 µg/kg every other day for 6 (cohorts A and B) or 10 (cohort C) doses in 21-day cycles. Cohorts B and C received dexamethasone prophylaxis against capillary leak syndrome (CLS). The most common treatment-related adverse events were reversible weight gain, hepatic transaminase elevation, and hypoalbuminemia. Dose-limiting CLS occurred in 2 of 4 patients receiving 30 µg/kg of moxetumomab pasudotox every other day for 6 doses. Incorporation of dexamethasone prevented further dose-limiting CLS. Six of 14 patients receiving 50 µg/kg of moxetumomab pasudotox for 10 doses developed hemolytic uremic syndrome (HUS), thrombotic microangiopathy (TMA), or HUS-like events, exceeding the MTCD. Treatment expansion at 40 µg/kg for 10 doses (n = 11) exceeded the MTCD because of 2 HUS/TMA/HUS-like events. Dose level 6B (ie, 50 µg/kg × 6 doses) was the MTCD, selected as the recommended phase 2 dose. Among 47 evaluable patients, an objective response rate of 32% was observed, including 11 (23%) composite complete responses, 5 of which were minimal residual disease negative by flow cytometry. Moxetumomab pasudotox showed a manageable safety profile and evidence of activity in relapsed or refractory childhood ALL. This trial was registered at www.clinicaltrials.gov as #NCT00659425. [Mh] Termos MeSH primário: Toxinas Bacterianas/uso terapêutico Exotoxinas/uso terapêutico Imunotoxinas/uso terapêutico Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia [Mh] Termos MeSH secundário: Adolescente Adulto Toxinas Bacterianas/efeitos adversos Toxinas Bacterianas/imunologia Toxinas Bacterianas/farmacocinética Síndrome de Vazamento Capilar/prevenção & controle Criança Pré-Escolar Dexametasona/uso terapêutico Exotoxinas/efeitos adversos Exotoxinas/imunologia Exotoxinas/farmacocinética Feminino Glucocorticoides/uso terapêutico Síndrome Hemolítico-Urêmica/induzido quimicamente Seres Humanos Hipoalbuminemia/induzido quimicamente Imunotoxinas/efeitos adversos Imunotoxinas/imunologia Imunotoxinas/farmacocinética Lactente Masculino Dose Máxima Tolerável Recidiva Local de Neoplasia/tratamento farmacológico Recidiva Local de Neoplasia/imunologia Recidiva Local de Neoplasia/patologia Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia Microangiopatias Trombóticas/induzido quimicamente Ganho de Peso/efeitos dos fármacos Adulto Jovem [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Glucocorticoids); 0 (Immunotoxins); 0 (Sialic Acid Binding Ig-like Lectin 2); 2NDX4B6N8F (immunotoxin HA22); 7S5I7G3JQL (Dexamethasone) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171007 [St] Status: MEDLINE [do] DOI: 10.1182/blood-2017-02-749101

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[PMID]: 28880913 [Au] Autor: Langley RJ; Ting YT; Clow F; Young PG; Radcliff FJ; Choi JM; Sequeira RP; Holtfreter S; Baker H; Fraser JD [Ad] Endereço: School of Medical Sciences, and The Maurice Wilkins Centre for Molecular Biodiscovery, the University of Auckland, Auckland, New Zealand. [Ti] Título: Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors. [So] Source: PLoS Pathog;13(9):e1006549, 2017 Sep. [Is] ISSN: 1553-7374 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs) and the Staphylococcal Superantigen-Like (SSL) exoproteins. The former are immunomodulatory toxins that induce a Vß-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences. The superantigenic properties of Staphylococcal enterotoxin-like X (SElX) have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac)-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK) assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae) two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX) reveals that SElX is a unique single-domain SAg. In summary, SElX is an 'SSL-like' SAg. [Mh] Termos MeSH primário: Enterotoxinas/metabolismo Exotoxinas/metabolismo Evasão da Resposta Imune/imunologia Infecções Estafilocócicas/metabolismo Staphylococcus aureus/metabolismo Fatores de Virulência/metabolismo [Mh] Termos MeSH secundário: Animais Células Cultivadas Seres Humanos Camundongos Infecções Estafilocócicas/imunologia Superantígenos/genética Fatores de Virulência/genética [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Enterotoxins); 0 (Exotoxins); 0 (Superantigens); 0 (Virulence Factors) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171017 [Lr] Data última revisão: 171017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170908 [St] Status: MEDLINE [do] DOI: 10.1371/journal.ppat.1006549

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[PMID]: 28854219 [Au] Autor: Shekarabi M; Hajikhani B; Salimi Chirani A; Fazeli M; Goudarzi M [Ad] Endereço: Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. [Ti] Título: Molecular characterization of vancomycin-resistant Staphylococcus aureus strains isolated from clinical samples: A three year study in Tehran, Iran. [So] Source: PLoS One;12(8):e0183607, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: INTRODUCTION: Emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant S. aureus (VRSA) strains has led to great concern in global public health in both developing and developed countries. This study investigated distribution and molecular characterization of VRSA strains in Tehran's hospitals using a combination of molecular typing methods. MATERIALS AND METHODS: A total of 1789 S. aureus isolates obtained between 2014 and 2017 and were characterized using antibiogram, SCCmec typing, spa typing, and multilocus-sequence typing. Resistance to vancomycin was determined by E-test method. After confirmation of the isolated VRSA strain, genetic analysis was performed by evaluating vanA and vanB genes presence.The presence of resistance (ermA, ermB, ermC, mupA, msrA, msrB, tetM, ant (4΄)-Ia, aac (6΄)-Ie/aph (2Ë�), aph (3΄)-IIIa) and toxin (etb, eta, pvl, tst) encoding genes was investigated by the polymerase chain reaction (PCR) technique. RESULTS: Of all S. aureus tested isolates, four isolates were confirmed as VRSA isolates and two isolates confirmed as VISA isolates. ST5- SCCmec II/t002 and ST239-SCCmec III/t037 strains had MIC values of 512µg/ml, ST239-SCCmec III/t037 and ST8-SCCmecIV/t008 strains had MIC values of 64µg/ml and ST22-SCCmec IV/t790 and ST239-SCCmec III/t030 strains had MIC values ≥ 8 µg/ml. pvl-encoding gene was confirmed in ST8-SCCmecIV/t008 and ST22-SCCmec IV/t790 strains. The isolates differed in the carriage of resistance and toxin encoding genes. CONCLUSIONS: The study revealed the existence of VRSA strains in capital of Iran, Tehran. To our knowledge, this is the first report of ST239-SCCmec III/t037 as VRSA strain. These findings support the need for future surveillance studies on VRSA strains to keep the emergence and transmission of these isolates to a minimum. [Mh] Termos MeSH primário: Infecção Hospitalar/microbiologia Infecções Estafilocócicas/microbiologia Staphylococcus aureus/genética Resistência a Vancomicina/genética [Mh] Termos MeSH secundário: Proteínas de Bactérias/genética Toxinas Bacterianas/genética Técnicas de Tipagem Bacteriana/métodos Carbono-Oxigênio Ligases/genética Infecção Hospitalar/epidemiologia Exotoxinas/genética Genes Bacterianos/genética Hospitais Seres Humanos Irã (Geográfico)/epidemiologia Leucocidinas/genética Testes de Sensibilidade Microbiana/métodos Proteínas Nucleares/genética Proteínas de Ligação às Penicilinas/genética Reação em Cadeia da Polimerase Infecções Estafilocócicas/epidemiologia Staphylococcus aureus/classificação Staphylococcus aureus/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Bacterial Toxins); 0 (Exotoxins); 0 (Leukocidins); 0 (Nuclear Proteins); 0 (Panton-Valentine leukocidin); 0 (Penicillin-Binding Proteins); 0 (VanA ligase, Bacteria); 0 (mecA protein, Staphylococcus aureus); 0 (mupA protein, Staphylococcus aureus); EC 6.1.- (Carbon-Oxygen Ligases) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171023 [Lr] Data última revisão: 171023 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170831 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0183607

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[PMID]: 28847519 [Au] Autor: Rogalski A; Soerensen C; Op den Brouw B; Lister C; Dashevsky D; Arbuckle K; Gloria A; Zdenek CN; Casewell NR; Gutiérrez JM; Wüster W; Ali SA; Masci P; Rowley P; Frank N; Fry BG [Ad] Endereço: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St Lucia QLD 4072 Australia. [Ti] Título: Differential procoagulant effects of saw-scaled viper (Serpentes: Viperidae: Echis) snake venoms on human plasma and the narrow taxonomic ranges of antivenom efficacies. [So] Source: Toxicol Lett;280:159-170, 2017 Oct 05. [Is] ISSN: 1879-3169 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Saw-scaled vipers (genus Echis) are one of the leading causes of snakebite morbidity and mortality in parts of Sub-Saharan Africa, the Middle East, and vast regions of Asia, constituting a public health burden exceeding that of almost any other snake genus globally. Venom-induced consumption coagulopathy, owing to the action of potent procoagulant toxins, is one of the most relevant clinical manifestations of envenomings by Echis spp. Clinical experience and prior studies examining a limited range of venoms and restricted antivenoms have demonstrated for some antivenoms an extreme lack of antivenom cross-reactivity between different species of this genus, sometimes resulting in catastrophic treatment failure. This study undertook the most comprehensive testing of Echis venom effects upon the coagulation of human plasma, and also the broadest examination of antivenom potency and cross-reactivity, to-date. 10 Echis species/populations and four antivenoms (two African, two Asian) were studied. The results indicate that the venoms are, in general, potently procoagulant but that the relative dependence on calcium or phospholipid cofactors is highly variable. Additionally, three out of the four antivenoms tested demonstrated only a very narrow taxonomic range of effectiveness in preventing coagulopathy, with only the SAIMR antivenom displaying significant levels of cross-reactivity. These results were in conflict with previous studies using prolonged preincubation of antivenom with venom to suggest effective cross-reactivity levels for the ICP Echi-Tab antivenom. These findings both inform upon potential clinical effects of envenomation in humans and highlight the extreme limitations of available treatment. It is hoped that this will spur efforts into the development of antivenoms with more comprehensive coverage for bites not only from wild snakes but also from specimens widely kept in zoological collections. [Mh] Termos MeSH primário: Coagulação Sanguínea/efeitos dos fármacos Plasma/fisiologia Venenos de Víboras/toxicidade Viperidae [Mh] Termos MeSH secundário: Animais Proteínas de Bactérias Exotoxinas Seres Humanos Superantígenos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Exotoxins); 0 (SpeJ protein, Streptococcus pyogenes); 0 (Superantigens); 0 (Viper Venoms) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171017 [Lr] Data última revisão: 171017 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170830 [St] Status: MEDLINE

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[PMID]: 28845032 [Au] Autor: Sumitomo T [Ad] Endereço: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry. [Ti] Título: Streptococcus pyogenes translocates across an epithelial barrier. [So] Source: Nihon Saikingaku Zasshi;72(3):213-218, 2017. [Is] ISSN: 1882-4110 [Cp] País de publicação: Japan [La] Idioma: jpn [Ab] Resumo: Streptococcus pyogenes is a ß-hemolytic organism responsible for a wide variety of human diseases that commonly occur as self-limiting purulent diseases of the pharynx and skin. Although the occurrence of invasive infections by S. pyogenes is rare, mortality rates remain high even with progressive medical therapy. As a prerequisite for causing the severe invasive disease, S. pyogenes must invade underlying sterile tissues by translocating across the epithelial barrier. In this study, streptolysin S and SpeB were identified as the novel factors that facilitate bacterial translocation via degradation of intercellular junctions. Furthermore, we found that S. pyogenes exploits host plasminogen for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. Here, I would like to show our study on bacterial translocation across the epithelial barrier through paracellular route. [Mh] Termos MeSH primário: Translocação Bacteriana Epitélio/microbiologia Infecções Estreptocócicas/microbiologia Streptococcus pyogenes/fisiologia Streptococcus pyogenes/patogenicidade [Mh] Termos MeSH secundário: Proteínas de Bactérias/fisiologia Translocação Bacteriana/genética Células Epiteliais/microbiologia Células Epiteliais/fisiologia Epitélio/fisiologia Exotoxinas/fisiologia Seres Humanos Junções Intercelulares/microbiologia Junções Intercelulares/fisiologia Plasminogênio/metabolismo Streptococcus pyogenes/genética Estreptolisinas/fisiologia Junções Íntimas/microbiologia Junções Íntimas/fisiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Bacterial Proteins); 0 (Exotoxins); 0 (Streptolysins); 0 (erythrogenic toxin); 0 (streptolysin S); 9001-91-6 (Plasminogen) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171015 [Lr] Data última revisão: 171015 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170829 [St] Status: MEDLINE [do] DOI: 10.3412/jsb.72.213

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