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Articles 1 - 30 of 35
Full-Text Articles in Life Sciences
Intratumoral Microbiome Of Adenoid Cystic Carcinomas And Comparison With Other Head And Neck Cancers, Tatiana V Karpinets, Yoshitsugu Mitani, Chia-Chi Chang, Xiaogang Wu, Xingzhi Song, Ivonne I Flores, Lauren K Mcdaniel, Yasmine M Hoballah, Fabiana J Veguilla, Renata Ferrarotto, Lauren E Colbert, Nadim J Ajami, Robert R Jenq, Jianhua Zhang, Andrew P Futreal, Adel K El-Naggar
Intratumoral Microbiome Of Adenoid Cystic Carcinomas And Comparison With Other Head And Neck Cancers, Tatiana V Karpinets, Yoshitsugu Mitani, Chia-Chi Chang, Xiaogang Wu, Xingzhi Song, Ivonne I Flores, Lauren K Mcdaniel, Yasmine M Hoballah, Fabiana J Veguilla, Renata Ferrarotto, Lauren E Colbert, Nadim J Ajami, Robert R Jenq, Jianhua Zhang, Andrew P Futreal, Adel K El-Naggar
Student and Faculty Publications
Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the …
Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding
Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding
School of Medicine Faculty Publications
Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …
The Power And Challenge Of Lipid (A)Symmetry Across The Membrane And Cell, Mikhail Bogdanov
The Power And Challenge Of Lipid (A)Symmetry Across The Membrane And Cell, Mikhail Bogdanov
Student and Faculty Publications
Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is …
Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou
Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou
Department of Biochemistry and Molecular Biology Faculty Papers
We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).
Evaluating The Microbial Experience Influence On Anti-Tumor Immune Response, Jessica A. Ensing
Evaluating The Microbial Experience Influence On Anti-Tumor Immune Response, Jessica A. Ensing
Student Summer Scholars Manuscripts
Despite the steady increase of hygienic standards, the CDC continues to report an increase of immune-mediated diseases such as allergies and asthma. Human avoidance of microbial exposure and subsequently less experienced immune systems may be the cause for this increase. We investigated if increased microbial exposure results in increased immunity to cancer (B16 melanoma) by measuring activated lymphocytes between two groups of C57Bl/6 mice: specific pathogen free (SPF) mice (which had little microbial exposure) and cohoused (COH) mice (which were exposed to numerous microbes). Previous research shows that the CoH mouse model mimics a human adult’s immune system, while the …
A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter
A Rapid Viability And Drug‑Susceptibility Assay Utilizing Mycobacteriophage As An Indicator Of Drug Susceptibilities Of Anti‑Tb Drugs Against Mycobacterium Smegmatis Mc2 155, Gillian Catherine Crowley, Jim O'Mahony, Aidan Coffey, Riona G. Sayers, Paul D. Cotter
Department of Biological Sciences Publications
Background: A rapid in-house TM4 mycobacteriophage-based assay, to identify multidrug resistance against various anti-tuberculosis drugs, using the fast-growing Mycobacterium smegmatis mc2 155 in a microtiter plate format was evaluated, based on phage viability assays. Methods: A variety of parameters were optimized before the study including the minimum incubation time for the drugs, phage and M. smegmatis mc2 155 to be in contact. An increase in phage numbers over 2 h was indicative that M. smegmatis mc2 155 is resistant to the drugs under investigation, however when phage numbers remained static, M. smegmatis mc2 155 found to …
Comparing The Effectiveness Of Alternative And Prescription Antibiotics Against Gram-Positive Bacteria, Rachel Jenkins, Roan Dickenson, Sam Turnbull, Marcela Torres
Comparing The Effectiveness Of Alternative And Prescription Antibiotics Against Gram-Positive Bacteria, Rachel Jenkins, Roan Dickenson, Sam Turnbull, Marcela Torres
Senior Theses
The rapid emergence of antibiotic-resistant bacteria is a global public health concern that threatens the efficacy of antibiotic drugs. We found that natural remedies, specifically coconut oil, honey and cinnamon essential oil, have the potential to be used as a clinical alternative to treat antibiotic-resistant infections. In this experiment, we performed a disk diffusion test and measured the area of inhibition of each treatment to compare the effectiveness of natural and prescription antibiotics. Cinnamon essential oil showed significantly greater antibiotic activity compared to a prescription treatment, amoxicillin. With bacterial resistance continuously expanding, more work needs to be done to determine …
Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman
Boosting Of Hiv Envelope Cd4 Binding Site Antibodies With Long Variable Heavy Third Complementarity Determining Region In The Randomized Double Blind Rv305 Hiv-1 Vaccine Trial, David Easterhoff, M. Anthony Moody, Daniela Fera, Hao Cheng, Margaret Ackerman
Dartmouth Scholarship
The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 …
Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe
Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe
Department of Biological Sciences Publications
The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …
Nucleoside-Diphosphate-Kinase Of P. Gingivalis Is Secreted From Epithelial Cells In The Absence Of A Leader Sequence Through A Pannexin-1 Interactome, Kalina Atanasova, Jungnam Lee, Joann Roberts, Kyulim Lee, David M. Ojcius, Özlem Yilmaz
Nucleoside-Diphosphate-Kinase Of P. Gingivalis Is Secreted From Epithelial Cells In The Absence Of A Leader Sequence Through A Pannexin-1 Interactome, Kalina Atanasova, Jungnam Lee, Joann Roberts, Kyulim Lee, David M. Ojcius, Özlem Yilmaz
All Dugoni School of Dentistry Faculty Articles
Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes. The mode(s) of NDK secretion is currently undefined, while extracellular translocation of bacterial NDKs is critical for avoidance of host pathogen clearance by opportunistic pathogens such as Porphyromonas gingivalis. P. gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis. Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7-receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co-cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation induced NDK recruitment to …
A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe
A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe
Department of Biological Sciences Publications
The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …
Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields
Application Of Β-Lactamase Reporter Fusions As An Indicator Of Effector Protein Secretion During Infections With The Obligate Intracellular Pathogen Chlamydia Trachomatis , Konrad E. Mueller, Kenneth A. Fields
Microbiology, Immunology, and Molecular Genetics Faculty Publications
Chlamydia spp. utilize multiple secretion systems, including the type III secretion system (T3SS), to deploy host-interactive effector proteins into infected host cells. Elucidation of secreted proteins has traditionally required ectopic expression in a surrogate T3SS followed by immunolocalization of endogenous candidate effectors to confirm secretion by chlamydiae. The ability to transform Chlamydia and achieve stable expression of recombinant gene products has enabled a more direct assessment of secretion. We adapted TEM-1 β-lactamase as a reporter system for assessment of chlamydial protein secretion. We provide evidence that this system facilitates visualization of secretion in the context of infection. Specifically, our findings …
Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator
Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator
Department of Biological Sciences Publications
It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …
Phages Of Non-Diary Lactococci: Isolation And Characterization Of Phi L47, A Phage Infecting The Grass Isolate Lactococcus Lactis Ssp Cremoris Dpc6860, Daniel Cavanagh, Caitríona M. Guinane, Horst Neve, Aidan Coffey, R. Paul Ross, Gerald F. Fitzgerald, Olivia Mcauliffe
Phages Of Non-Diary Lactococci: Isolation And Characterization Of Phi L47, A Phage Infecting The Grass Isolate Lactococcus Lactis Ssp Cremoris Dpc6860, Daniel Cavanagh, Caitríona M. Guinane, Horst Neve, Aidan Coffey, R. Paul Ross, Gerald F. Fitzgerald, Olivia Mcauliffe
Department of Biological Sciences Publications
Lactococci isolated from non-dairy sources have been found to possess enhanced metabolic activity when compared to dairy strains. These capabilities may be harnessed through the use of these strains as starter or adjunct cultures to produce more diverse flavor profiles in cheese and other dairy products. To understand the interactions between these organisms and the phages that infect them, a number of phages were isolated against lactococcal strains of non-dairy origin. One such phage, ΦL47, was isolated from a sewage sample using the grass isolate L. lactis ssp. cremoris DPC6860 as a host. Visualization of phage virions by transmission electron …
Mycological Study For A Management Plan Of A Neotropical Show Cave (Brazil), Erika Linzi Silva Taylor, Maria Aparecida De Resende Stoianoff, Rodrigo Lopes Ferreira
Mycological Study For A Management Plan Of A Neotropical Show Cave (Brazil), Erika Linzi Silva Taylor, Maria Aparecida De Resende Stoianoff, Rodrigo Lopes Ferreira
International Journal of Speleology
Caves are stable environments with characteristics favoring the development of microorganisms. The allocthonous input of organic matter and microbes into the warm Neotropical caves may favor the development of filamentous fungi, including pathogenic species. Histoplasma capsulatum is a pathogenic species commonly found in caves and associated with bat and bird guano. Many Brazilian caves have been historically visited due to scenic and religious tourism. The objective of this study was to perform a microbiology study for a management plan of a show cave in Brazil, focusing on the presence and distribution of pathogenic and opportunistic fungi in the cave. Statistics …
Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole
Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole
Dartmouth Scholarship
Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …
Molecular Diagnostics: The Changing Culture Of Medical Microbiology, Susan Bullman, Brigid Lucey, Roy D. Sleator
Molecular Diagnostics: The Changing Culture Of Medical Microbiology, Susan Bullman, Brigid Lucey, Roy D. Sleator
Department of Biological Sciences Publications
Diagnostic molecular biology is arguably the fastest growing area in current laboratory-based medicine. Growth of the so called ‘omics’ technologies has, over the last decade, led to a gradual migration away from the ‘one test, one pathogen’ paradigm, toward multiplex approaches to infectious disease diagnosis, which have led to significant improvements in clinical diagnostics and ultimately improved patient care.
Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator
Emerging Dynamics Of Human Campylobacteriosis In Southern Ireland, Susan Bullman, Daniel Corcoran, James O'Leary, Derry O'Hare, Brigid Lucey, Roy D. Sleator
Department of Biological Sciences Publications
Infections with Campylobacter spp. pose a significant health burden worldwide. The significance of Campylobacter jejuni/Campylobacter coli infection is well appreciated but the contribution of non-C. jejuni/C. coli spp. to human gastroenteritis is largely unknown. In this study, we employed a two-tiered molecular study on 7194 patient faecal samples received by the Microbiology Department in Cork University Hospital during 2009. The first step, using EntericBio® (Serosep), a multiplex PCR system, detected Campylobacter to the genus level. The second step, utilizing Campylobacter species-specific PCR identified to the species level. A total of 340 samples were confirmed as Campylobacter genus positive, 329 of …
Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator
Campylobacter Ureolyticus: An Emerging Gastrointestinal Pathogen?, Susan Bullman, Daniel Corcoran, James O'Leary, Brigid Lucey, Deirdre Byrne, Roy D. Sleator
Department of Biological Sciences Publications
A total of 7194 faecal samples collected over a 1-year period from patients presenting with diarrhoea were screened for Campylobacter spp. using EntericBios, a multiplex-PCR system. Of 349 Campylobacter-positive samples, 23.8% were shown to be Campylobacter ureolyticus, using a combination of 16S rRNA gene analysis and highly specific primers targeting the HSP60 gene of this organism. This is, to the best of our knowledge, the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis and may suggest a role for this organism as an emerging enteric pathogen.
Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator
Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator
Department of Biological Sciences Publications
Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.
Role Of Flgt In Anchoring The Flagellum Of Vibrio Cholerae, Raquel M. Martinez, Brooke A. Jude, Thomas J. Kirn, Karen Skorupski, Ronald K. Taylor
Role Of Flgt In Anchoring The Flagellum Of Vibrio Cholerae, Raquel M. Martinez, Brooke A. Jude, Thomas J. Kirn, Karen Skorupski, Ronald K. Taylor
Dartmouth Scholarship
Flagellar motility has long been regarded as an important virulence factor. In Vibrio cholerae, the single polar flagellum is essential for motility as well as for proper attachment and colonization. In this study, we demonstrate that the novel flagellar protein FlgT is involved in anchoring the flagellum to the V. cholerae cell. A screen for novel colonization factors by use of TnphoA mutagenesis identified flgT. An in-frame deletion of flgT established that FlgT is required for attachment, colonization, and motility. Transmission electron microscopy revealed that while the flgT mutant is capable of assembling a phenotypically normal flagellum, …
Levels Of The Secreted Vibrio Cholerae Attachment Factor Gbpa Are Modulated By Quorum-Sensing-Induced Proteolysis, Brooke A. Jude, Raquel M. Martinez, Karen Skorupski, Ronald K. Taylor
Levels Of The Secreted Vibrio Cholerae Attachment Factor Gbpa Are Modulated By Quorum-Sensing-Induced Proteolysis, Brooke A. Jude, Raquel M. Martinez, Karen Skorupski, Ronald K. Taylor
Dartmouth Scholarship
Vibrio cholerae is the etiologic agent of cholera in humans. Intestinal colonization occurs in a stepwise fashion, initiating with attachment to the small intestinal epithelium. This attachment is followed by expression of the toxin-coregulated pilus, microcolony formation, and cholera toxin (CT) production. We have recently characterized a secreted attachment factor, GlcNAc binding protein A (GbpA), which functions in attachment to environmental chitin sources as well as to intestinal substrates. Studies have been initiated to define the regulatory network involved in GbpA induction. At low cell density, GbpA was detected in the culture supernatant of all wild-type (WT) strains examined. In …
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Characterization Of Two Outer Membrane Proteins, Flgo And Flgp, That Influence Vibrio Cholerae Motility, Raquel M. Martinez, Madushini N. Dharmasena, Thomas J. Kirn, Ronald K. Taylor
Dartmouth Scholarship
Vibrio cholerae is highly motile by the action of a single polar flagellum. The loss of motility reduces the infectivity of V. cholerae, demonstrating that motility is an important virulence factor. FlrC is the sigma-54-dependent positive regulator of flagellar genes. Recently, the genes VC2206 (flgP) and VC2207 (flgO) were identified as being regulated by FlrC via a microarray analysis of an flrC mutant (D. C. Morris, F. Peng, J. R. Barker, and K. E. Klose, J. Bacteriol. 190:231-239, 2008). FlgP is reported to be an outer membrane lipoprotein required for motility that functions as a colonization factor. The study reported …
Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel
Long-Distance Delivery Of Bacterial Virulence Factors By Pseudomonas Aeruginosa Outer Membrane Vesicles, Jennifer M. Bomberger, Daniel P. Maceachran, Bonita A. Coutermarsh, Siying Ye, George A. O'Toole, Bruce A. Stanton, Frederick M. Ausubel
Dartmouth Scholarship
Bacteria use a variety of secreted virulence factors to manipulate host cells, thereby causing significant morbidity and mortality. We report a mechanism for the long-distance delivery of multiple bacterial virulence factors, simultaneously and directly into the host cell cytoplasm, thus obviating the need for direct interaction of the pathogen with the host cell to cause cytotoxicity. We show that outer membrane–derived vesicles (OMV) secreted by the opportunistic human pathogen Pseudomonas aeruginosa deliver multiple virulence factors, including β-lactamase, alkaline phosphatase, hemolytic phospholipase C, and Cif, directly into the host cytoplasm via fusion of OMV with lipid rafts in the host plasma …
Salicylic Acid Activates Sigma Factor B By Rsbu-Dependent And -Independent Mechanisms, Marco Palma, Arnold Bayer, Leon I. Kupferwasser, Tammy Joska, Michael R. Yeaman, Ambrose Cheung
Salicylic Acid Activates Sigma Factor B By Rsbu-Dependent And -Independent Mechanisms, Marco Palma, Arnold Bayer, Leon I. Kupferwasser, Tammy Joska, Michael R. Yeaman, Ambrose Cheung
Dartmouth Scholarship
Salicylic acid (SAL) may impact Staphylococcus aureus virulence by activating the sigB operon (rsbU-V-W-sigB), thus leading to reductions in alpha-toxin production and decreased fibronectin binding (L. I. Kupferwasser et al., J. Clin. Investig. 112:222-233, 2003). As these prior studies were performed in strain RN6390 (an rsbU mutant) and its rsbU-repaired variant, SH1000, the current investigation was designed to determine if the SAL effect occurs via rsbU- and/or rsbV-dependent pathways in an rsbU-intact S. aureus strain (FDA486). We thus quantified the transcription from two sigB-dependent promoters (asp23 and sarA P3) in FDA486 in response to SAL exposure in vitro, using isogenic …
The Role Of Cd4 T Cells In The Pathogenesis Of Murine Aids, Wen Li, William R. Green
The Role Of Cd4 T Cells In The Pathogenesis Of Murine Aids, Wen Li, William R. Green
Dartmouth Scholarship
LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of …
Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole
Keeping Their Options Open: Acute Versus Persistent Infections, S. Furukawa, S. L. Kuchma, G. A. O'Toole
Dartmouth Scholarship
No abstract provided.
Transposon Disruption Of The Complex I Nadh Oxidoreductase Gene (Snod) In Staphylococcus Aureus Is Associated With Reduced Susceptibility To The Microbicidal Activity Of Thrombin-Induced Platelet Microbicidal Protein 1, Arnold S. Bayer, Peter Mcnamara, Michael R. Yeaman, Natalie Lucindo, Tiffanny Jones, Ambrose L. Cheung
Transposon Disruption Of The Complex I Nadh Oxidoreductase Gene (Snod) In Staphylococcus Aureus Is Associated With Reduced Susceptibility To The Microbicidal Activity Of Thrombin-Induced Platelet Microbicidal Protein 1, Arnold S. Bayer, Peter Mcnamara, Michael R. Yeaman, Natalie Lucindo, Tiffanny Jones, Ambrose L. Cheung
Dartmouth Scholarship
The cationic molecule thrombin-induced platelet microbicidal protein 1 (tPMP-1) exerts potent activity against Staphylococcus aureus. We previously reported that a Tn551 S. aureus transposon mutant, ISP479R, and two bacteriophage back-transductants, TxA and TxB, exhibit reduced in vitro susceptibility to tPMP-1 (tPMP-1(r)) compared to the parental strain, ISP479C (V. Dhawan, M. R. Yeaman, A. L. Cheung, E. Kim, P. M. Sullam, and A. S. Bayer, Infect. Immun. 65:3293-3299, 1997). In the current study, the genetic basis for tPMP-1(r) in these mutants was identified. GenBank homology searches using sequence corresponding to chromosomal DNA flanking Tn551 mutant strains showed that the fourth gene …
Rhamnolipids Modulate Swarming Motility Patterns Of Pseudomonas Aeruginosa, Nicky C. Caiazza, Robert M. Q. Shanks, G. A. O'Toole
Rhamnolipids Modulate Swarming Motility Patterns Of Pseudomonas Aeruginosa, Nicky C. Caiazza, Robert M. Q. Shanks, G. A. O'Toole
Dartmouth Scholarship
Pseudomonas aeruginosa is capable of twitching, swimming, and swarming motility. The latter form of translocation occurs on semisolid surfaces, requires functional flagella and biosurfactant production, and results in complex motility patterns. From the point of inoculation, bacteria migrate as defined groups, referred to as tendrils, moving in a coordinated manner capable of sensing and responding to other groups of cells. We were able to show that P. aeruginosa produces extracellular factors capable of modulating tendril movement, and genetic analysis revealed that modulation of these movements was dependent on rhamnolipid biosynthesis. An rhlB mutant (deficient in mono- and dirhamnolipid production) and …
Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor
Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor
Dartmouth Scholarship
The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation …