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Full-Text Articles in Medicine and Health Sciences
Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan
Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan
Dartmouth Scholarship
The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …
Characterization And Quantification Of The Fungal Microbiome In Serial Samples From Individuals With Cystic Fibrosis, Sven D. Willger, Sharon L. Grim, Emily L. Dolben, Anna Shipunova, Thomas H. Hampton, Hillary G. Morrison, Laura M. Filkins, George A. O'Toole, Lisa A. Moulton, Alix Ashare, Mitchell L. Sogin, Deborah A. Hogan
Characterization And Quantification Of The Fungal Microbiome In Serial Samples From Individuals With Cystic Fibrosis, Sven D. Willger, Sharon L. Grim, Emily L. Dolben, Anna Shipunova, Thomas H. Hampton, Hillary G. Morrison, Laura M. Filkins, George A. O'Toole, Lisa A. Moulton, Alix Ashare, Mitchell L. Sogin, Deborah A. Hogan
Dartmouth Scholarship
Background: Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required. Results: We characterized the fungi and bacteria in expectorated sputa from six …
Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin
Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin
Dartmouth Scholarship
Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …
Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg
Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg
Dartmouth Scholarship
Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses …
Lack Of Protection Following Passive Transfer Of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies, Anne-Sophie Dugast, Ying Chan, Michelle Hoffner, Anna Licht, Joseph Nkolola, Hualin Li, Hendrik Streeck, Todd J. Suscovich, Musie Ghebremichael, Margaret E. Ackerman, Dan H. Barouch, Galit Alter
Lack Of Protection Following Passive Transfer Of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies, Anne-Sophie Dugast, Ying Chan, Michelle Hoffner, Anna Licht, Joseph Nkolola, Hualin Li, Hendrik Streeck, Todd J. Suscovich, Musie Ghebremichael, Margaret E. Ackerman, Dan H. Barouch, Galit Alter
Dartmouth Scholarship
Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred …
The Microbiome In Pediatric Cystic Fibrosis Patients: The Role Of Shared Environment Suggests A Window Of Intervention, Thomas H. Hampton, Deanna M. Green, Garry R. Cutting, Hilary G. Morrison, Mitchell L. Sogin, Alex H. Gifford, Bruce A. Stanton, George A. O’Toole
The Microbiome In Pediatric Cystic Fibrosis Patients: The Role Of Shared Environment Suggests A Window Of Intervention, Thomas H. Hampton, Deanna M. Green, Garry R. Cutting, Hilary G. Morrison, Mitchell L. Sogin, Alex H. Gifford, Bruce A. Stanton, George A. O’Toole
Dartmouth Scholarship
Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the …
Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota
Human And Helicobacter Pylori Coevolution Shapes The Risk Of Gastric Disease, Nuri Kodaman, Alvaro Pazos, Barbara G. Schneider, M. Blanca Piazuelo, Robertino Mera, Rafal S. Sobota
Dartmouth Scholarship
Helicobacter pylori is the principal cause of gastric cancer, the second leading cause of cancer mortality worldwide. However, H. pylori prevalence generally does not predict cancer incidence. To determine whether coevolution between host and pathogen influences disease risk, we examined the association between the severity of gastric lesions and patterns of genomic variation in matched human and H. pylori samples. Patients were recruited from two geographically distinct Colombian populations with significantly different incidences of gastric cancer, but virtually identical prevalence of H. pylori infection. All H. pylori isolates contained the genetic signatures of multiple ancestries, with an ancestral African cluster …