The Experts below are selected from a list of 1023 Experts worldwide ranked by ideXlab platform
Ronan K Carroll - One of the best experts on this subject based on the ideXlab platform.
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staphylococcus aureus trigger factor is involved in biofilm formation and cooperates with the chaperone PPIB
Journal of Bacteriology, 2021Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Gillian G Null, Andrew Frey, Emily C Marino, Donald L Holzschu, Lindsey N Shaw, Ronan K CarrollAbstract:ABSTRACT Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that assist in protein folding around proline-peptide bonds, and they often possess chaperone activity. Staphylococcus aureus encodes three PPIases, i.e., PrsA, PPIB, and trigger factor (TF). Previous work by our group demonstrated a role for both PrsA and PPIB in S. aureus; however, TF remains largely unstudied. Here, we identify a role for TF in S. aureus biofilm formation and demonstrate cooperation between TF and the cytoplasmic PPIase PPIB. Mutation of the tig gene (encoding TF) led to reduced biofilm development in vitro but no significant attenuation of virulence in a mouse model of infection. To investigate whether TF possesses chaperone activity, we analyzed the ability of a tig mutant to survive acid and base stress. While there was no significant decrease for a tig mutant, a PPIBtig double mutant exhibited significant decreases in cell viability after acid and base challenges. We then demonstrated that a PPIB tig double mutant had exacerbated phenotypes in vitro and in vivo, compared to either single mutant. Finally, in vivo immunoprecipitation of epitope-tagged PPIB revealed that PPIB interacted with 4 times the number of proteins when TF was absent from the cell, suggesting that it may be compensating for the loss of TF. Interestingly, the only proteins found to interact with TF were TF itself, fibronectin-binding protein B (FnBPB), and the chaperone protein ClpB. Collectively, these results support the first phenotype for S. aureus TF and demonstrate a greater network of cooperation between chaperone proteins in Staphylococcus aureus. IMPORTANCES. aureus encodes a large number of virulence factors that aid the bacterium in survival and pathogenesis. These virulence factors have a wide variety of functions; however, they must all be properly secreted in order to be functional. Bacterial chaperone proteins often assist in secretion by trafficking proteins to secretion machinery or assisting in proper protein folding. Here, we report that the S. aureus chaperone TF contributes to biofilm formation and cooperates with the chaperone PPIB to regulate S. aureus virulence processes. These data highlight the first known role for TF in S. aureus and suggest that S. aureus chaperone proteins may be involved in a greater regulatory network in the cell.
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novel regulation of alpha toxin and the phenol soluble modulins by peptidyl prolyl cis trans isomerase enzymes in staphylococcus aureus
Toxins, 2019Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Emily Trzeciak, Gillian G Null, Ronan K CarrollAbstract:Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PPIB and PrsA) that are involved in the regulation of virulence determinants and have shown that PPIB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a PPIB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the PPIB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a PPIB mutant strain has reduced levels of the phenol-soluble modulins and that both PPIB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PPIB and PrsA. Results suggest a novel role for PPIB in S. aureus protein secretion. Collectively, our results demonstrate that PPIB and PrsA influence S. aureus toxins via distinct mechanisms, and that PPIB but not PrsA contributes to disease.
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the intracellular cyclophilin PPIB contributes to the virulence of staphylococcus aureus independently of its peptidyl prolyl cis trans isomerase activity
Infection and Immunity, 2018Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Marcus A Wittekind, Ronan K CarrollAbstract:The Staphylococcus aureus cyclophilin PPIB is an intracellular peptidyl prolyl cis/trans isomerase (PPIase) that has previously been shown to contribute to secreted nuclease and hemolytic activity. In this study, we investigated the contribution of PPIB to S. aureus virulence. Using a murine abscess model of infection, we demonstrated that a PPIB mutant is attenuated for virulence. We went on to investigate the mechanism through which PPIB protein contributes to virulence, in particular the contribution of PPIB PPIase activity. We determined the amino acid residues that are important for PPIB PPIase activity and showed that a single amino acid substitution (F64A) completely abrogates PPIase activity. Using purified PPIB F64A protein in vitro, we showed that PPIase activity only partially contributes to Nuc refolding and that PPIB also possesses PPIase-independent activity. Using allelic exchange, we introduced the F64A substitution onto the S. aureus chromosome, generating a strain that produces enzymatically inactive PPIB. Analysis of the PPIB F64A strain revealed that PPIase activity is not required for hemolysis of human blood or virulence in a mouse. Together, these results demonstrate that PPIB contributes to S. aureus virulence via a mechanism unrelated to prolyl isomerase activity.
Jhon Tailor Rengifomosquera - One of the best experts on this subject based on the ideXlab platform.
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nuevo registro y ampliacion de distribucion geografica para agalychnis psilopygion anura hylidae phyllomedusinae en el choco biogeografico de colombia
Revista Biodiversidad Neotropical, 2013Co-Authors: Pablo Palacios Rodriguez, Karen Quesadamosquera, Jhon Tailor RengifomosqueraAbstract:We report a new locality for Agalychnis psilopygion (Cannatella 1980) in Biological Research Permanent Plot ( PPIB ), located in the center of the department of Choco; all three individuals were found associated with a permanent water body product human intervention in leaves of bushes , sharing habitat with A. spurrelli , A. aff terranova , Hypsiboas pellucens , H. rubracylus, Craugastor fitzingeri, Dendrosophus phleobodes and Lithobates vaillantis . This record extends the geographic range for the species about 190 km from the type locality. The discovery of this species listed by the Convention on International Trade in Endangered Species of Fauna and Flora in Appendix II also lacks ecological, biological and phylogenetic relationships in the area of influence of the PPIB in the village of Salero is important in terms of conservation of forests for the preservation of amphibians of the Colombian Pacific lowlands.
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nuevo registro y ampliacion de distribucion geografica para agalychnis psilopygion anura hylidae phyllomedusinae en el choco biogeografico de colombia new record and geographic distribution expansion for agalychnis psilopygion anura hylidae phyllomed
2013Co-Authors: Pablo Palaciosrodriguez, Karen Quesadamosquera, Jhon Tailor RengifomosqueraAbstract:We report a new locality for Agalychnis psilopygion (Cannatella 1980) in Biological Research Permanent Plot ( PPIB ), located in the center of the department of Choco; all three individuals were found associated with a permanent water body product human intervention in leaves of bushes , sharing habitat with A. spurrelli, A. aff terranova, Hypsiboas pellucens, H. rubracylus, Craugastor fitzingeri, Dendrosophus phleobodes and Lithobates vaillantis. This record extends the geographic range for the species about 190 km from the type locality. The discovery of this species listed by the Convention on International Trade in Endangered Species of Fauna and Flora in Appendix II also lacks ecological, biological and phylogenetic relationships in the area of influence of the PPIB in the village of Salero is important in terms of conservation of forests for the preservation of amphibians of the Colombian Pacific lowlands.
Furtado, Clara Fernanda Barbirato - One of the best experts on this subject based on the ideXlab platform.
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INVESTIGAÇÃO DE MUTAÇÕES NOS GENES LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1 CAUSADORAS DA OSTEOGÊNESE IMPERFEITA RECESSIVA
Universidade Federal do Espírito Santo, 2015Co-Authors: Furtado, Clara Fernanda BarbiratoAbstract:INVESTIGAÇÃO DE MUTAÇÕES NOS GENES LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1 CAUSADORAS DA OSTEOGÊNESE IMPERFEITA RECESSIV
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Investigação de mutações nos genes LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1 causadoras da osteogênese imperfeita recessiva
Doutorado em Biotecnologia, 2015Co-Authors: Furtado, Clara Fernanda BarbiratoAbstract:A Osteogênese Imperfeita (OI) é uma doença clínica e geneticamente heterogênea caracterizada, predominantemente, por fragilidade e deformidade ósseas e por fraturas recorrentes. A maioria dos casos de OI resulta de mutações autossômicas dominantes nos genes COL1A1 e COL1A2, que codificam as cadeias formadoras do colágeno tipo I, principal proteína dos ossos. Nos últimos anos, um número crescente de casos decorrentes de mutações recessivas vem sendo relatado em genes associados à biossíntese do colágeno tipo I ou à formação e a mineralização óssea, como os genes LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1. Mutações nesses genes, em geral, levam ao desenvolvimento de fenótipos graves e letais de OI. Neste trabalho, foram analisados os genes LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1 de 25 pacientes com OI utilizando-se as técnicas de SSCP e sequenciamento. Ao todo, 29 variações genéticas foram detectadas, entre mutações e polimorfismos. Das onze variações encontradas no gene LEPRE1, estão a já bem descrita c.1080+1G>T e as mutações potencialmente deletérias c.2024G>A / p.Lys363Glu e c.1501C>T / p.Arg501Trp. No gene FKBP10, foi encontrada a também descrita duplicação c.831dupC, além da c.1546G>A / p.Leu516Phe, predita como causadora da doença. Observou-se que os genes FKBP10 e LEPRE1 contêm as principais mutações encontradas neste trabalho e sugere-se que os mesmos sejam preferencialmente analisados em estudos de triagem e identificação de mutações em OI. Até o momento, não existem relatos de mutações nos genes LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 e SERPINF1 em pacientes brasileiros e este trabalho fornece novas informações sobre os aspectos genéticos da OI recessivaOsteogenesis Imperfecta (OI) is a clinically and genetically heterogeneous disease predominantly characterized by bone fragility and deformity and recurrent fractures. Most cases of OI result of autosomal dominant mutations in COL1A1 and COL1A2 genes that encode the chains forming type I collagen, the main protein in bones. In the past few years, an increasing number of cases due to recessive mutations has been reported in genes associated with the biosynthesis of type I collagen or to the formation and bone mineralization, such as LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 and SERPINF1. Mutations in these genes, in general, lead to the development of severe and lethal OI phenotypes. In this work, LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 and SERPINF1 of 25 OI patients were analyzed using SSCP and automated sequencing. Altogether, 29 genetic variations were detected, mutations and polymorphisms. Among the eleven variants found in LEPRE1 gene, there are the already well described c.1080 + 1G> T and the potentially deleterious mutations c.2024G> A / p.Lys363Glu and c.1501C> T / p.Arg501Trp . In FKBP10 gene, the previously described duplication c.831dupC, and c.1546G>A / p.Leu516Phe, predicted to be disease causing, were detected. It was observed that FKBP10 and LEPRE1 contain the most important mutations found in the patients studied in this work and it is suggested that LEPRE1 and FKBP10 should be preferably analyzed in studies of screening and identification of mutations in patients with OI. To date, there are no reports of mutations in LEPRE1, CRTAP, PPIB, FKBP10, SERPINH1 and SERPINF1 genes in Brazilian patients and this study provides new information on the genetic aspects of recessive OI
Ximena Montano - One of the best experts on this subject based on the ideXlab platform.
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analysis of sars cov 2 infection associated cell entry proteins ace2 cd147 ppia and PPIB in datasets from non sars cov 2 infected neuroblastoma patients as potential prognostic and infection biomarkers in neuroblastoma
Biochemistry and biophysics reports, 2021Co-Authors: Brandon Bergsneider, Elise Bailey, Yusuf Ahmed, Namrata Gogineni, Derek Huntley, Ximena MontanoAbstract:SARS-CoV-2 viral contagion has given rise to a worldwide pandemic. Although most children experience minor symptoms from SARS-CoV-2 infection, some have severe complications including Multisystem Inflammatory Syndrome in Children. Neuroblastoma patients may be at higher risk of severe infection as treatment requires immunocompromising chemotherapy and SARS-CoV-2 has demonstrated tropism for nervous cells. To date, there is no sufficient epidemiological data on neuroblastoma patients with SARS-CoV-2. Therefore, we evaluated datasets of non-SARS-CoV-2 infected neuroblastoma patients to assess for key genes involved with SARS-CoV-2 infection as possible neuroblastoma prognostic and infection biomarkers. We hypothesized that ACE2, CD147, PPIA and PPIB, which are associated with viral-cell entry, are potential biomarkers for poor prognosis neuroblastoma and SARS-CoV-2 infection. We have analysed three publicly available neuroblastoma gene expression datasets to understand the specific molecular susceptibilities that high-risk neuroblastoma patients have to the virus. Gene Expression Omnibus (GEO) {"type":"entrez-geo","attrs":{"text":"GSE49711","term_id":"49711"}}GSE49711 and GEO {"type":"entrez-geo","attrs":{"text":"GSE62564","term_id":"62564"}}GSE62564 are the microarray and RNA-Seq data, respectively, from 498 neuroblastoma samples published as part of the Sequencing Quality Control initiative. TARGET, contains microarray data from 249 samples and is part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. ACE2, CD147, PPIA and PPIB were identified through their involvement in both SARS-CoV-2 infection and cancer pathogenesis. In-depth statistical analysis using Kaplan-Meier, differential gene expression, and Cox multivariate regression analysis, demonstrated that overexpression of ACE2, CD147, PPIA and PPIB is significantly associated with poor-prognosis neuroblastoma samples. These results were seen in the presence of amplified MYCN, unfavourable tumour histology and in patients older than 18 months of age. Previously, we have shown that high levels of the nerve growth factor receptor NTRK1 together with low levels of the phosphatase PTPN6 and TP53 are associated with increased relapse-free survival of neuroblastoma patients. Interestingly, low levels of expression of ACE2, CD147, PPIA and PPIB are associated with this NTRK1-PTPN6-TP53 module, suggesting that low expression levels of these genes are associated with good prognosis. These findings have implications for clinical care and therapeutic treatment. The upregulation of ACE2, CD147, PPIA and PPIB in poor-prognosis neuroblastoma samples suggests that these patients may be at higher risk of severe SARS-CoV-2 infection. Importantly, our findings reveal ACE2, CD147, PPIA and PPIB as potential biomarkers and therapeutic targets for neuroblastoma.
Rebecca A Keogh - One of the best experts on this subject based on the ideXlab platform.
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staphylococcus aureus trigger factor is involved in biofilm formation and cooperates with the chaperone PPIB
Journal of Bacteriology, 2021Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Gillian G Null, Andrew Frey, Emily C Marino, Donald L Holzschu, Lindsey N Shaw, Ronan K CarrollAbstract:ABSTRACT Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that assist in protein folding around proline-peptide bonds, and they often possess chaperone activity. Staphylococcus aureus encodes three PPIases, i.e., PrsA, PPIB, and trigger factor (TF). Previous work by our group demonstrated a role for both PrsA and PPIB in S. aureus; however, TF remains largely unstudied. Here, we identify a role for TF in S. aureus biofilm formation and demonstrate cooperation between TF and the cytoplasmic PPIase PPIB. Mutation of the tig gene (encoding TF) led to reduced biofilm development in vitro but no significant attenuation of virulence in a mouse model of infection. To investigate whether TF possesses chaperone activity, we analyzed the ability of a tig mutant to survive acid and base stress. While there was no significant decrease for a tig mutant, a PPIBtig double mutant exhibited significant decreases in cell viability after acid and base challenges. We then demonstrated that a PPIB tig double mutant had exacerbated phenotypes in vitro and in vivo, compared to either single mutant. Finally, in vivo immunoprecipitation of epitope-tagged PPIB revealed that PPIB interacted with 4 times the number of proteins when TF was absent from the cell, suggesting that it may be compensating for the loss of TF. Interestingly, the only proteins found to interact with TF were TF itself, fibronectin-binding protein B (FnBPB), and the chaperone protein ClpB. Collectively, these results support the first phenotype for S. aureus TF and demonstrate a greater network of cooperation between chaperone proteins in Staphylococcus aureus. IMPORTANCES. aureus encodes a large number of virulence factors that aid the bacterium in survival and pathogenesis. These virulence factors have a wide variety of functions; however, they must all be properly secreted in order to be functional. Bacterial chaperone proteins often assist in secretion by trafficking proteins to secretion machinery or assisting in proper protein folding. Here, we report that the S. aureus chaperone TF contributes to biofilm formation and cooperates with the chaperone PPIB to regulate S. aureus virulence processes. These data highlight the first known role for TF in S. aureus and suggest that S. aureus chaperone proteins may be involved in a greater regulatory network in the cell.
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novel regulation of alpha toxin and the phenol soluble modulins by peptidyl prolyl cis trans isomerase enzymes in staphylococcus aureus
Toxins, 2019Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Emily Trzeciak, Gillian G Null, Ronan K CarrollAbstract:Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes that catalyze the cis-to-trans isomerization around proline bonds, allowing proteins to fold into their correct confirmation. Previously, we identified two PPIase enzymes in Staphylococcus aureus (PPIB and PrsA) that are involved in the regulation of virulence determinants and have shown that PPIB contributes to S. aureus virulence in a murine abscess model of infection. Here, we further examine the role of these PPIases in S. aureus virulence and, in particular, their regulation of hemolytic toxins. Using murine abscess and systemic models of infection, we show that a PPIB mutant in a USA300 background is attenuated for virulence but that a prsA mutant is not. Deletion of the PPIB gene leads to decreased bacterial survival in macrophages and nasal epithelial cells, while there is no significant difference when prsA is deleted. Analysis of culture supernatants reveals that a PPIB mutant strain has reduced levels of the phenol-soluble modulins and that both PPIB and prsA mutants have reduced alpha-toxin activity. Finally, we perform immunoprecipitation to identify cellular targets of PPIB and PrsA. Results suggest a novel role for PPIB in S. aureus protein secretion. Collectively, our results demonstrate that PPIB and PrsA influence S. aureus toxins via distinct mechanisms, and that PPIB but not PrsA contributes to disease.
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the intracellular cyclophilin PPIB contributes to the virulence of staphylococcus aureus independently of its peptidyl prolyl cis trans isomerase activity
Infection and Immunity, 2018Co-Authors: Rebecca A Keogh, Rachel L Zapf, Richard E Wiemels, Marcus A Wittekind, Ronan K CarrollAbstract:The Staphylococcus aureus cyclophilin PPIB is an intracellular peptidyl prolyl cis/trans isomerase (PPIase) that has previously been shown to contribute to secreted nuclease and hemolytic activity. In this study, we investigated the contribution of PPIB to S. aureus virulence. Using a murine abscess model of infection, we demonstrated that a PPIB mutant is attenuated for virulence. We went on to investigate the mechanism through which PPIB protein contributes to virulence, in particular the contribution of PPIB PPIase activity. We determined the amino acid residues that are important for PPIB PPIase activity and showed that a single amino acid substitution (F64A) completely abrogates PPIase activity. Using purified PPIB F64A protein in vitro, we showed that PPIase activity only partially contributes to Nuc refolding and that PPIB also possesses PPIase-independent activity. Using allelic exchange, we introduced the F64A substitution onto the S. aureus chromosome, generating a strain that produces enzymatically inactive PPIB. Analysis of the PPIB F64A strain revealed that PPIase activity is not required for hemolysis of human blood or virulence in a mouse. Together, these results demonstrate that PPIB contributes to S. aureus virulence via a mechanism unrelated to prolyl isomerase activity.
