The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Lucy J. Hathaway - One of the best experts on this subject based on the ideXlab platform.
-
Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Susanne Aebi, Peter Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
-
Streptococcus pneumoniae Proteins Amia, AliA, and AliB Bind Peptides Found in Ribosomal Proteins of Other Bacterial Species.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Lucy J. HathawayAbstract:The nasopharynx is frequently colonized by both commensal and pathogenic bacteria including Streptococcus pneumoniae (pneumococcus). Pneumococcus is an important pathogen responsible for bacterial meningitis and community acquired pneumonia but is also commonly an asymptomatic colonizer of the nasopharynx. Understanding interactions between microbes may provide insights into pathogenesis. Here we investigated the ability of the three oligopeptide-binding proteins Amia, AliA and AliB of an ATP-binding cassette transporter of pneumococcus to detect short peptides found in other bacterial species. We found three possible peptide ligands for Amia and four each for AliA and AliB of which two for each protein matched ribosomal proteins of other bacterial species. Using synthetic peptides we confirmed the following binding: Amia binds peptide AKTIKITQTR, matching 50S ribosomal subunit protein L30, AliA binds peptide FNEMQPIVDRQ, matching 30S ribosomal protein S20 and AliB binds peptide AIQSEKARKHN, matching 30S ribosomal protein S20, without excluding the possibility of binding of the other peptides. These Ami-AliA/AliB peptide ligands are found in multiple species in the class of Gammaproteobacteria which includes common colonizers of the nostrils and nasopharynx. Binding such peptides may enable pneumococcus to detect and respond to neighboring species in its environment and is a potential mechanism for interspecies communication and environmental surveillance.
-
Data_Sheet_3_Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.PDF
2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Suzanne Aebi, Peter W. M. Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
Thilo Stehle - One of the best experts on this subject based on the ideXlab platform.
-
structure function analysis of staphylococcus aureus amidase reveals the determinants of peptidoglycan recognition and cleavage
Journal of Biological Chemistry, 2014Co-Authors: Felix Michael Buttner, Mulugeta Nega, Friedrich Götz, Sebastian Zoll, Thilo StehleAbstract:The bifunctional major autolysin AtlA of Staphylococcus aureus cleaves the bacterium's peptidoglycan network (PGN) at two distinct sites during cell division. Deletion of the enzyme results in large cell clusters with disordered division patterns, indicating that AtlA could be a promising target for the development of new antibiotics. One of the two functions of AtlA is performed by the N-acetylmuramyl-l-alanine amidase Amia, which cleaves the bond between the carbohydrate and the peptide moieties of PGN. To establish the structural requirements of PGN recognition and the enzymatic mechanism of cleavage, we solved the crystal structure of the catalytic domain of Amia (Amia-cat) in complex with a peptidoglycan-derived ligand at 1.55 A resolution. The peptide stem is clearly visible in the structure, forming extensive contacts with protein residues by docking into an elongated groove. Less well defined electron density and the analysis of surface features indicate likely positions of the carbohydrate backbone and the pentaglycine bridge. Substrate specificity analysis supports the importance of the pentaglycine bridge for fitting into the binding cleft of Amia-cat. PGN of S. aureus with l-lysine tethered with d-alanine via a pentaglycine bridge is completely hydrolyzed, whereas PGN of Bacillus subtilis with meso-diaminopimelic acid directly tethered with d-alanine is not hydrolyzed. An active site mutant, H370A, of Amia-cat was completely inactive, providing further support for the proposed catalytic mechanism of Amia. The structure reported here is not only the first of any bacterial amidase in which both the PGN component and the water molecule that carries out the nucleophilic attack on the carbonyl carbon of the scissile bond are present; it is also the first peptidoglycan amidase complex structure of an important human pathogen.
Edward H. Shortliffe - One of the best experts on this subject based on the ideXlab platform.
-
Amia board white paper definition of biomedical informatics and specification of core competencies for graduate education in the discipline
Journal of the American Medical Informatics Association, 2012Co-Authors: Casimir A Kulikowski, Edward H. Shortliffe, Leanne M Currie, Peter L Elkin, Lawrence Hunter, Todd R Johnson, Ira J Kalet, Leslie A Lenert, Mark A Musen, Judy G OzboltAbstract:The Amia biomedical informatics (BMI) core competencies have been designed to support and guide graduate education in BMI, the core scientific discipline underlying the breadth of the field's research, practice, and education. The core definition of BMI adopted by Amia specifies that BMI is 'the interdisciplinary field that studies and pursues the effective uses of biomedical data, information, and knowledge for scientific inquiry, problem solving and decision making, motivated by efforts to improve human health.' Application areas range from bioinformatics to clinical and public health informatics and span the spectrum from the molecular to population levels of health and biomedicine. The shared core informatics competencies of BMI draw on the practical experience of many specific informatics sub-disciplines. The Amia BMI analysis highlights the central shared set of competencies that should guide curriculum design and that graduate students should be expected to master.
-
Amia president's column: Amia and HIT policy activities
Journal of the American Medical Informatics Association : JAMIA, 2011Co-Authors: Edward H. ShortliffeAbstract:In my inaugural column in January 2011, I described the recent efforts by Amia to assess its current and future roles, and the ways in which we are perceived by our members and by external groups. Insights from formal and informal surveys have led to a number of changes, including our new logo and branding, our new website, and our explicit efforts to broaden our membership within the informatics and health-information-technology communities. One element in the surveys was particularly surprising to us, however. Our members expressed a desire for Amia to be more involved in public policy work and to represent the field visibly and effectively as legislation and regulations are developed and promulgated. Yet this is an area in which Amia has evolved dramatically in recent years, and our role and effectiveness in Washington, DC and with major policy groups are well known to the organization's leadership and to our colleagues in other societies. Since it appears that some of our members are unaware of the significant work that Amia does in the policy arena, I would like to devote this issue's column to providing a brief update on this topic. From its inception more than two decades ago, Amia has had a public policy committee, and its volunteer members did what they could to represent the field and its interests and to inform other members about evolving policy issues. Fortunately, with the 2004 recruitment of Dr Don Detmer to his role as President and CEO of the association, we had full-time …
-
Amia president's message.
Journal of the American Medical Informatics Association : JAMIA, 2011Co-Authors: Edward H. ShortliffeAbstract:Although informatics is often viewed externally as a new discipline, the field has a rich history that dates back at least to the 1960s, with a well-known seminal paper appearing even earlier.1 Amia itself was created in the late 1980s when three separate informatics organizations, with overlapping interests, saw the value in combining their missions and activities in a single, larger, and more cohesive organization. Those three nonprofit corporate entities ( SCAMC : the Symposium on Computer Applications in Medical Care; AAMSI : the American Association for Medical Systems and Informatics; and ACMI : the American College of Medical Informatics) dissolved their own charters and pooled resources to form a new organization that would incorporate the activities of all three. SCAMC became the Amia Annual Symposium, which we hold every fall, AAMSI became the membership organization, and ACMI was re-created within Amia as its College of elected Fellows. All three activities continue to thrive to this day, as does our annual spring meeting, which owes its roots to the annual AAMSI meeting, which was held at that time of year. The world of informatics has changed dramatically since Amia was formed, and the association has accordingly evolved as well. That evolution requires introspection and decisions—ones that need to reflect our roots and to reaffirm the critical importance of disciplines such as computer science that gave rise to informatics, as well as to embrace change when appropriate. Amia's roots are firmly planted in academia, corporate research, hospitals, and other clinical practice settings—plus the government agencies (notably the NLM …
-
don e detmer and the american medical informatics association an appreciation
Journal of the American Medical Informatics Association, 2009Co-Authors: Edward H. Shortliffe, Elaine B Steen, Karen Greenwood, David W. Bates, Meryl Bloomrosen, Charles Safran, Paul C TangAbstract:Don E. Detmer has served as President and Chief Executive Officer of the American Medical Informatics Association (Amia) for the past five years, helping to set a course for the organization and demonstrating remarkable leadership as Amia has evolved into a vibrant and influential professional association. On the occasion of Dr. Detmer's retirement, we fondly reflect on his professional life and his many contributions to biomedical informatics and, more generally, to health care in the U.S. and globally.
Fauzy Nasher - One of the best experts on this subject based on the ideXlab platform.
-
Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Susanne Aebi, Peter Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
-
Streptococcus pneumoniae Proteins Amia, AliA, and AliB Bind Peptides Found in Ribosomal Proteins of Other Bacterial Species.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Lucy J. HathawayAbstract:The nasopharynx is frequently colonized by both commensal and pathogenic bacteria including Streptococcus pneumoniae (pneumococcus). Pneumococcus is an important pathogen responsible for bacterial meningitis and community acquired pneumonia but is also commonly an asymptomatic colonizer of the nasopharynx. Understanding interactions between microbes may provide insights into pathogenesis. Here we investigated the ability of the three oligopeptide-binding proteins Amia, AliA and AliB of an ATP-binding cassette transporter of pneumococcus to detect short peptides found in other bacterial species. We found three possible peptide ligands for Amia and four each for AliA and AliB of which two for each protein matched ribosomal proteins of other bacterial species. Using synthetic peptides we confirmed the following binding: Amia binds peptide AKTIKITQTR, matching 50S ribosomal subunit protein L30, AliA binds peptide FNEMQPIVDRQ, matching 30S ribosomal protein S20 and AliB binds peptide AIQSEKARKHN, matching 30S ribosomal protein S20, without excluding the possibility of binding of the other peptides. These Ami-AliA/AliB peptide ligands are found in multiple species in the class of Gammaproteobacteria which includes common colonizers of the nostrils and nasopharynx. Binding such peptides may enable pneumococcus to detect and respond to neighboring species in its environment and is a potential mechanism for interspecies communication and environmental surveillance.
-
Data_Sheet_3_Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.PDF
2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Suzanne Aebi, Peter W. M. Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
Manfred Heller - One of the best experts on this subject based on the ideXlab platform.
-
Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Susanne Aebi, Peter Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
-
Streptococcus pneumoniae Proteins Amia, AliA, and AliB Bind Peptides Found in Ribosomal Proteins of Other Bacterial Species.
Frontiers in microbiology, 2018Co-Authors: Fauzy Nasher, Manfred Heller, Lucy J. HathawayAbstract:The nasopharynx is frequently colonized by both commensal and pathogenic bacteria including Streptococcus pneumoniae (pneumococcus). Pneumococcus is an important pathogen responsible for bacterial meningitis and community acquired pneumonia but is also commonly an asymptomatic colonizer of the nasopharynx. Understanding interactions between microbes may provide insights into pathogenesis. Here we investigated the ability of the three oligopeptide-binding proteins Amia, AliA and AliB of an ATP-binding cassette transporter of pneumococcus to detect short peptides found in other bacterial species. We found three possible peptide ligands for Amia and four each for AliA and AliB of which two for each protein matched ribosomal proteins of other bacterial species. Using synthetic peptides we confirmed the following binding: Amia binds peptide AKTIKITQTR, matching 50S ribosomal subunit protein L30, AliA binds peptide FNEMQPIVDRQ, matching 30S ribosomal protein S20 and AliB binds peptide AIQSEKARKHN, matching 30S ribosomal protein S20, without excluding the possibility of binding of the other peptides. These Ami-AliA/AliB peptide ligands are found in multiple species in the class of Gammaproteobacteria which includes common colonizers of the nostrils and nasopharynx. Binding such peptides may enable pneumococcus to detect and respond to neighboring species in its environment and is a potential mechanism for interspecies communication and environmental surveillance.
-
Data_Sheet_3_Peptide Ligands of Amia, AliA, and AliB Proteins Determine Pneumococcal Phenotype.PDF
2018Co-Authors: Fauzy Nasher, Manfred Heller, Fernando Aguilar, Suzanne Aebi, Peter W. M. Hermans, Lucy J. HathawayAbstract:The Ami-AliA/AliB oligopeptide permease of Streptococcus pneumoniae has been suggested to play a role in environmental sensing and colonisation of the nasopharynx by this human bacterial pathogen by binding peptides derived from bacterial neighbours of other species in the microbiota. Here, we investigated the effects of the peptide ligands of the permease’s substrate binding proteins Amia, AliA, and AliB on pneumococcal phenotype. Amia and AliA ligands reduced pneumococcal growth, increased biofilm production and reduced capsule size. In contrast, AliB ligand increased growth and greatly increased bacterial chain length. A decrease in transformation rate was observed in response to all three peptides. Changes in protein expression were also observed, particularly those associated with metabolism and cell wall synthesis. Understanding interspecies bacterial communication and its effect on development of colonising versus invasive phenotypes has the potential to reveal new targets to tackle and prevent pneumococcal infections.
