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Search Results: 1 - 10 of 297812 matches for " J Maxwell Dow "
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Microbiota and Metabolite Profiling Reveal Specific Alterations in Bacterial Community Structure and Environment in the Cystic Fibrosis Airway during Exacerbation
Kate B. Twomey, Mark Alston, Shi-Qi An, Oisin J. O'Connell, Yvonne McCarthy, David Swarbreck, Melanie Febrer, J. Maxwell Dow, Barry J. Plant, Robert P. Ryan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082432
Abstract: Chronic polymicrobial infections of the lung are the foremost cause of morbidity and mortality in cystic fibrosis (CF) patients. The composition of the microbial flora of the airway alters considerably during infection, particularly during patient exacerbation. An understanding of which organisms are growing, their environment and their behaviour in the airway is of importance for designing antibiotic treatment regimes and for patient prognosis. To this end, we have analysed sputum samples taken from separate cohorts of CF and non-CF subjects for metabolites and in parallel, and we have examined both isolated DNA and RNA for the presence of 16S rRNA genes and transcripts by high-throughput sequencing of amplicon or cDNA libraries. This analysis revealed that although the population size of all dominant orders of bacteria as measured by DNA- and RNA- based methods are similar, greater discrepancies are seen with less prevalent organisms, some of which we associated with CF for the first time. Additionally, we identified a strong relationship between the abundance of specific anaerobes and fluctuations in several metabolites including lactate and putrescine during patient exacerbation. This study has hence identified organisms whose occurrence within the CF microbiome has been hitherto unreported and has revealed potential metabolic biomarkers for exacerbation.
Novel Cyclic di-GMP Effectors of the YajQ Protein Family Control Bacterial Virulence
Shi-qi An,Delphine L. Caly,Yvonne McCarthy,Sarah L. Murdoch,Joseph Ward,Melanie Febrer,J. Maxwell Dow,Robert P. Ryan
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004429
Abstract: Bis-(3′,5′) cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (Kd~2 μM). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.
Acquisition and Evolution of Plant Pathogenesis–Associated Gene Clusters and Candidate Determinants of Tissue-Specificity in Xanthomonas
Hong Lu, Prabhu Patil, Marie-Anne Van Sluys, Frank F. White, Robert P. Ryan, J. Maxwell Dow, Pablo Rabinowicz, Steven L. Salzberg, Jan E. Leach, Ramesh Sonti, Volker Brendel, Adam J. Bogdanove
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003828
Abstract: Background Xanthomonas is a large genus of plant-associated and plant-pathogenic bacteria. Collectively, members cause diseases on over 392 plant species. Individually, they exhibit marked host- and tissue-specificity. The determinants of this specificity are unknown. Methodology/Principal Findings To assess potential contributions to host- and tissue-specificity, pathogenesis-associated gene clusters were compared across genomes of eight Xanthomonas strains representing vascular or non-vascular pathogens of rice, brassicas, pepper and tomato, and citrus. The gum cluster for extracellular polysaccharide is conserved except for gumN and sequences downstream. The xcs and xps clusters for type II secretion are conserved, except in the rice pathogens, in which xcs is missing. In the otherwise conserved hrp cluster, sequences flanking the core genes for type III secretion vary with respect to insertion sequence element and putative effector gene content. Variation at the rpf (regulation of pathogenicity factors) cluster is more pronounced, though genes with established functional relevance are conserved. A cluster for synthesis of lipopolysaccharide varies highly, suggesting multiple horizontal gene transfers and reassortments, but this variation does not correlate with host- or tissue-specificity. Phylogenetic trees based on amino acid alignments of gum, xps, xcs, hrp, and rpf cluster products generally reflect strain phylogeny. However, amino acid residues at four positions correlate with tissue specificity, revealing hpaA and xpsD as candidate determinants. Examination of genome sequences of xanthomonads Xylella fastidiosa and Stenotrophomonas maltophilia revealed that the hrp, gum, and xcs clusters are recent acquisitions in the Xanthomonas lineage. Conclusions/Significance Our results provide insight into the ancestral Xanthomonas genome and indicate that differentiation with respect to host- and tissue-specificity involved not major modifications or wholesale exchange of clusters, but subtle changes in a small number of genes or in non-coding sequences, and/or differences outside the clusters, potentially among regulatory targets or secretory substrates.
The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants
Lisa C Crossman, Virginia C Gould, J Maxwell Dow, Georgios S Vernikos, Aki Okazaki, Mohammed Sebaihia, David Saunders, Claire Arrowsmith, Tim Carver, Nicholas Peters, Ellen Adlem, Arnaud Kerhornou, Angela Lord, Lee Murphy, Katharine Seeger, Robert Squares, Simon Rutter, Michael A Quail, Mari-Adele Rajandream, David Harris, Carol Churcher, Stephen D Bentley, Julian Parkhill, Nicholas R Thomson, Matthew B Avison
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-4-r74
Abstract: The genome of the bacteremia-associated isolate S. maltophilia K279a is 4,851,126 bp and of high G+C content. The sequence reveals an organism with a remarkable capacity for drug and heavy metal resistance. In addition to a number of genes conferring resistance to antimicrobial drugs of different classes via alternative mechanisms, nine resistance-nodulation-division (RND)-type putative antimicrobial efflux systems are present. Functional genomic analysis confirms a role in drug resistance for several of the novel RND efflux pumps. S. maltophilia possesses potentially mobile regions of DNA and encodes a number of pili and fimbriae likely to be involved in adhesion and biofilm formation that may also contribute to increased antimicrobial drug resistance.The panoply of antimicrobial drug resistance genes and mobile genetic elements found suggests that the organism can act as a reservoir of antimicrobial drug resistance determinants in a clinical environment, which is an issue of considerable concern.The rise of antimicrobial drug resistance in bacteria is one of the biggest threats to healthcare provision in the developed world. Few new antimicrobial drugs are undergoing clinical trials, and almost none are effective against Gram-negative multi-drug resistant (MDR) pathogens [1]. A return to the pre-antibiotic era is a possibility, and for some infections is the current reality [2].Antimicrobial resistance in historically common pathogens is usually either acquired on a mobile genetic element or results from a mutation [3]. However, some opportunistic pathogens are intrinsically resistant to the actions of a number of antimicrobial classes. These tend to be of environmental origin, and their intrinsic drug resistance determinants either provide resistance to antibiotics produced by competitors, or represent broad-spectrum methods for removing toxic compounds or waste products that, by chance, protect against antimicrobials [3,4]. It is known that established opportuni
An Orphan Chemotaxis Sensor Regulates Virulence and Antibiotic Tolerance in the Human Pathogen Pseudomonas aeruginosa
Heather Pearl McLaughlin, Delphine L. Caly, Yvonne McCarthy, Robert Patrick Ryan, John Maxwell Dow
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0042205
Abstract: The synthesis of virulence factors by pathogenic bacteria is highly regulated and occurs in response to diverse environmental cues. An array of two component systems (TCSs) serves to link perception of different cues to specific changes in gene expression and/or bacterial behaviour. Those TCSs that regulate functions associated with virulence represent attractive targets for interference in anti-infective strategies for disease control. We have previously identified PA2572 as a putative response regulator required for full virulence of Pseudomonas aeruginosa, the opportunistic human pathogen, to Galleria mellonella (Wax moth) larvae. Here we have investigated the involvement of candidate sensors for signal transduction involving PA2572. Mutation of PA2573, encoding a probable methyl-accepting chemotaxis protein, gave rise to alterations in motility, virulence, and antibiotic resistance, functions which are also controlled by PA2572. Comparative transcriptome profiling of mutants revealed that PA2572 and PA2573 regulate expression of a common set of 49 genes that are involved in a range of biological functions including virulence and antibiotic resistance. Bacterial two-hybrid analysis indicated a REC-dependent interaction between PA2572 and PA2573 proteins. Finally expression of PA2572 in the PA2573 mutant background restored virulence to G. mellonella towards wild-type levels. The findings indicate a role for the orphan chemotaxis sensor PA2573 in the regulation of virulence and antibiotic tolerance in P. aeruginosa and indicate that these effects are exerted in part through signal transduction involving PA2572.
Vegetation of Doi Tung, Chiang Rai Province, Northern
J. F. Maxwell
Maejo International Journal of Science and Technology , 2007,
Abstract: The climate of Doi Tung, Chiang Rai Province, is monsoonal with three distinctseasons, viz. cool-dry, hot-dry, and rainy. The elevation ranges from c. 350-1525m and mostof the bedrock is limestone and granite. Vegetation below c. 1000m is mostly deciduous,while above this it is evergreen. A mixed evergreen + deciduous facies is present on thelimestone peaks (up to 1425m). Forest destruction as well as settlements are widespread,thus creating increasingly severe problems with water resources, soil quality and stability, andbiodiversity. The planting on pine monocultures in deforested areas 20 years ago in uplandgranite areas has resulted in much environmental degradation which requires immediaterectification.
A Convergent Reformulation of QCD Perturbation Theory
C. J. Maxwell
Physics , 1997, DOI: 10.1016/S0370-2693(97)00882-4
Abstract: We propose a generalization of Grunberg's method of effective charges in which, starting with the effective charge for some dimensionless QCD observable dependent on the single energy scale $Q, R(Q)$, we introduce an infinite set of auxiliary effective charges, each one describing the sub-asymptotic Q-evolution of the immediately preceding effective charge. The corresponding infinite set of coupled integrated effective charge beta-function equations may be truncated. The resulting approximations for $R(Q)$ are the convergents of a continued function. They are manifestly RS-invariant and converge to a limit equal to the Borel sum of the standard asymptotic perturbation series in $\alpha_s({\mu^2})$, with remaining ambiguities due to infra-red renormalons. There are close connections with Pad{\'e} approximation.
Large-order Behaviour of the QCD Adler D-function in Planar Approximation
C. J. Maxwell
Physics , 1997, DOI: 10.1016/S0370-2693(97)00860-5
Abstract: We consider the structure of the leading ultra-violet (UV) renormalon singularity associated with the QCD vacuum polarization Adler D-function, in the approximation that only planar Feynman diagrams are retained. This ``planar approximation'' results in some simplifications, in particular three of the four potential contributions from four-fermion operators are shown to be absent. We are able to obtain a fully normalized result for the leading $n\to\infty$ behaviour of the portion of perturbative coefficients proportional to $N_f^{n-r} N^r$, for SU(N) QCD with $N_f$ quark flavours.
Complete renormalization group improvement of QCD perturbation theory
C. J. Maxwell
Physics , 1998,
Abstract: We suggest that at any given order of Feynman diagram calculation all renormalization group (RG)-predictable terms should be resummed to all-orders. This ``complete'' RG-improvement (CORGI) serves to separate the perturbation series into infinite subsets of terms which when summed are renormalization scheme (RS)-invariant. Crucially all ultraviolet logarithms involving the dimensionful parameter, Q, on which the observable depends are resummed, thereby building the correct Q-dependence. There are close connections with the effective charge approach of Grunberg.
Complete Renormalization Group Improvement- Avoiding Scale Dependence in QCD Predictions
C. J. Maxwell
Physics , 1999, DOI: 10.1016/S0920-5632(00)00545-4
Abstract: We show that dimensionful renormalization scheme parameters such as the renormalization or factorization scale can be completely eliminated from perturbative QCD predictions provided that all the ultraviolet logarithms involving the physical energy scale Q are completely resummed.
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