Imperial College London

DrMichaelCox

Faculty of MedicineNational Heart & Lung Institute

Research Associate
 
 
 
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Contact

 

+44 (0)20 7594 7974michael.cox1 Website

 
 
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Location

 

413Guy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

57 results found

Salter SJ, Cox MJ, Turek EM, Calus ST, Cookson WO, Moffatt MF, Turner P, Parkhill J, Loman NJ, Walker AWet al., 2014, Reagent and laboratory contamination can critically impact sequence-based microbiome analyses, BMC Biology, Vol: 12, ISSN: 1741-7007

BackgroundThe study of microbial communities has been revolutionised in recent years by the widespread adoption of culture independent analytical techniques such as 16S rRNA gene sequencing and metagenomics. One potential confounder of these sequence-based approaches is the presence of contamination in DNA extraction kits and other laboratory reagents.ResultsIn this study we demonstrate that contaminating DNA is ubiquitous in commonly used DNA extraction kits and other laboratory reagents, varies greatly in composition between different kits and kit batches, and that this contamination critically impacts results obtained from samples containing a low microbial biomass. Contamination impacts both PCR-based 16S rRNA gene surveys and shotgun metagenomics. We provide an extensive list of potential contaminating genera, and guidelines on how to mitigate the effects of contamination.ConclusionsThese results suggest that caution should be advised when applying sequence-based techniques to the study of microbiota present in low biomass environments. Concurrent sequencing of negative control samples is strongly advised.

Journal article

Sim K, Shaw AG, Randell P, Cox MJ, McClure ZE, Li M-S, Haddad M, Langford PR, Cookson WOCM, Moffatt MF, Kroll JSet al., 2014, Dysbiosis Anticipating Necrotizing Enterocolitis in Very Premature Infants, Clinical Infectious Diseases, Vol: 60, Pages: 389-397, ISSN: 1537-6591

Journal article

Molyneaux PL, Cox MJ, Willis-Owen SAG, Mallia P, Russell KE, Russel A-M, Murphy E, Johnston SL, Schwarte DA, Wells AU, Cookson WOC, Maher TM, Moffatt MFet al., 2014, The Role of Bacteria in the Pathogenesis and Progression of Idiopathic Pulmonary Fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 906-913, ISSN: 1535-4970

Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung diseaseof unknown cause that leads to respiratory failure and death within 5 yearsof diagnosis. Overt respiratory infection and immunosuppression carrya high morbidity and mortality, and polymorphisms in genes related toepithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesisand progression of IPF.Methods: We prospectively enrolled patients diagnosed with IPFaccording to international criteria together with healthy smokers,nonsmokers, and subjectswithmoderate chronic obstructive pulmonarydisease as control subjects. Subjects underwent bronchoalveolarlavage (BAL), from which genomic DNA was isolated. The V3–V5region of the bacterial 16S rRNA gene was amplified, allowingquantification of bacterial load and identification of communities by 16SrRNA quantitative polymerase chain reaction and pyrosequencing. Measurements and Main Results: Sixty-five patients with IPFhad double the burden of bacteria in BAL fluid compared with 44 controlsubjects. Baseline bacterial burden predicted the rate of decline in lungvolume and risk of death and associated independently with thers35705950 polymorphism of the MUC5B mucin gene, a proven hostsusceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality readsfrom all subjects.WeidentifiedHaemophilus, Streptococcus,Neisseria, andVeillonella spp. to be more abundant in cases than control subjects.Regression analyses indicated that these specific operational taxonomicunits as well as bacterial burden associated independently with IPF.Conclusions: IPF is characterized by an increased bacterial burdenin BAL that predicts decline in lung function and death. Trials ofantimicrobial therapy are needed to determine if microbial burdenis pathogenic in the disease.

Journal article

Salter, Susannah Cox, Michael J Turek, Elena M Calus, Szymon T Cookson, William O Moffatt, Miriam F Turner, Paul Parkhill, Julian Loman, Nick Walker, Alan Wet al., 2014, Reagent contamination can critically impact sequence-based microbiome analyses, bioRxiv

Susannah Salter1,7 (sb18{at}sanger.ac.uk), Michael J Cox2 (michael.cox1{at}imperial.ac.uk), Elena M Turek2 (elena.turek11{at}imperial.ac.uk), Szymon T Calus3 (s.t.calus{at}bham.ac.uk), William O Cookson2 (w.cookson{at}imperial.ac.uk), Miriam F Moffatt2 (m.moffatt{at}imperial.ac.uk), Paul Turner4 (pault{at}tropmedres.ac), Julian Parkhill5 (parkhill{at}sanger.ac.uk), Nick Loman3 (n.j.loman{at}bham.ac.uk) and Alan W Walker6 (alan.walker{at}abdn.ac.uk) 1 Wellcome Trust Sanger Institute; 2 Molecular Genetics and Genomics, National Heart and Lung Institute, Imperial College London; 3 Institute of Microbiology and Infection, University of Birmingham; 4 Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford; 5 Pathogen Genomics, Wellcome Trust Sanger Institute; 6 Microbiology Group, Rowett Institute of Nutrition and Health, University of Aberdeen ↵* Corresponding author; email: sb18{at}sanger.ac.uk AbstractThe study of microbial communities has been revolutionised in recent years by the widespread adoption of culture independent analytical techniques such as 16S rRNA gene sequencing and metagenomics. One potential confounder of these sequence-based approaches is the presence of contamination in DNA extraction kits and other laboratory reagents. In this study we demonstrate that contaminating DNA is ubiquitous in commonly used DNA extraction kits, varies greatly in composition between different kits and kit batches, and that this contamination critically impacts results obtained from samples containing a low microbial biomass. Contamination impacts both PCR-based 16S rRNA gene surveys and shotgun metagenomics. These results suggest that caution should be advised when applying sequence-based techniques to the study of microbiota present in low biomass environments. We provide an extensive list of potential contaminating genera, and guidelines on how to mitigate the effects of contamination. Concurrent sequencing of negative control samples i

Journal article

Molyneaux PL, Cox MJ, Mallia P, Johnston SL, Moffatt MF, Cookson WOC, Maher TMet al., 2013, THE ROLE OF THE RESPIRATORY MICROBIOME IN IDIOPATHIC PULMONARY FIBROSIS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A22, ISSN: 0040-6376

Conference paper

Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SAG, Homola D, Trujillo-Torralbo M-B, Elkin S, Kon OM, Cookson WOC, Moffatt MF, Johnston SLet al., 2013, Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 188, Pages: 1224-1231, ISSN: 1073-449X

Journal article

Cox MJ, Cookson WOCM, Moffatt MF, 2013, Sequencing the human microbiome in health and disease, HUMAN MOLECULAR GENETICS, Vol: 22, Pages: R88-R94, ISSN: 0964-6906

Journal article

Duff RM, Simmonds NJ, Davies JC, Wilson R, Alton EW, Pantelidis P, Cox MJ, Cookson WOCM, Bilton D, Moffatt MFet al., 2013, A molecular comparison of microbial communities in bronchiectasis and cystic fibrosis, EUROPEAN RESPIRATORY JOURNAL, Vol: 41, Pages: 991-993, ISSN: 0903-1936

Journal article

Cardenas PA, Cooper PJ, Cox MJ, Chico M, Arias C, Moffatt MF, Cookson WOet al., 2012, Upper Airways Microbiota in Antibiotic-Naive Wheezing and Healthy Infants from the Tropics of Rural Ecuador, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Cox MJ, Schaefer H, Nightingale PD, McDonald IR, Murrell JCet al., 2012, Diversity of methyl halide-degrading microorganisms in oceanic and coastal waters, FEMS MICROBIOLOGY LETTERS, Vol: 334, Pages: 111-118, ISSN: 0378-1097

Journal article

Sim K, Cox MJ, Wopereis H, Martin R, Knol J, Li MS, Cookson WO, Moffatt MF, Kroll JSet al., 2012, Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing, PLoS One, Vol: 7, Pages: e32543-e32543

The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, 'bifidobacteria-optimised' universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria.

Journal article

Cox MJ, Jones AL, Loebinger MR, Duff RM, Simmonds NJ, Davies JC, Wilson R, Alton EW, Cookson WOCM, Bilton D, Moffatt MFet al., 2011, MUCOIDY AND THE MICROBIOME: COMMUNITY COMPOSITION IN RELATION TO THE PRESENCE OF CULTURABLE, MUCOID PSEUDOMONAS AERUGINOSA, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: A24-A24, ISSN: 0040-6376

Conference paper

Cox MJ, Duff RM, Simmonds NJ, Davies J, Wilson R, Alton E, Pantolidis P, Cookson WO, Bilton D, Moffatt MFet al., 2011, Comparison Of The Microbiomes Of Two Chronic Airway Diseases Using High-Throughput Sequencing, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Edwards JL, Smith DL, Connolly J, McDonald JE, Cox MJ, Joint IR, Edwards C, McCarthy AJet al., 2010, Identification of Carbohydrate Metabolism Genes in the Metagenome of a Marine biofilm Community Shown to be Dominated by Gammaproteobacteria and Bacteroidetes, Genes, Pages: 371-384

Journal article

Fujimura KE, Johnson CC, Ownby DR, Cox MJ, Brodie EL, Havstad SL, Zoratti EM, Woodcroft KJ, Bobbitt KR, Wegienka G, Boushey HA, Lynch SVet al., 2010, Man's best friend? The effect of pet ownership on house dust microbial communities., The Journal of allergy and clinical immunology, Vol: 126, Pages: 410-412.e3

Journal article

Roediger FC, Slusher NA, Allgaier S, Cox MJ, Pletcher SD, Goldberg AN, Lynch SVet al., 2010, Nucleic acid extraction efficiency and bacterial recovery from maxillary sinus mucosal samples obtained by brushing or biopsy, American Journal of Rhinology and Allergy, Vol: 24, Pages: 263-265

Journal article

Huang YJ, Kim E, Cox MJ, Brodie EL, Brown R, Wiener-Kronish JP, Lynch SVet al., 2010, A persistent and diverse airway microbiota present during chronic obstructive pulmonary disease exacerbations., Omics : a journal of integrative biology, Vol: 14, Pages: 9-59

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are a major source of morbidity and contribute significantly to healthcare costs. Although bacterial infections are implicated in nearly 50% of exacerbations, only a handful of pathogens have been consistently identified in COPD airways, primarily by culture-based methods, and the bacterial microbiota in acute exacerbations remains largely uncharacterized. The aim of this study was to comprehensively profile airway bacterial communities using a culture-independent microarray, the 16S rRNA PhyloChip, of a cohort of COPD patients requiring ventilatory support and antibiotic therapy for exacerbation-related respiratory failure. PhyloChip analysis revealed the presence of over 1,200 bacterial taxa representing 140 distinct families, many previously undetected in airway diseases; bacterial community composition was strongly influenced by the duration of intubation. A core community of 75 taxa was detected in all patients, many of which are known pathogens. Bacterial community diversity in COPD airways is substantially greater than previously recognized and includes a number of potential pathogens detected in the setting of antibiotic exposure. Comprehensive assessment of the COPD airway microbiota using high-throughput, culture-independent methods may prove key to understanding the relationships between airway bacterial colonization, acute exacerbation, and clinical outcomes in this and other chronic inflammatory airway diseases.

Journal article

Cox MJ, Allgaier M, Taylor B, Baek MS, Huang YJ, Daly RA, Karaoz U, Andersen GL, Brown R, Fujimura KE, Wu B, Tran D, Koff J, Kleinhenz ME, Nielson D, Brodie EL, Lynch SVet al., 2010, Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients., PloS one, Vol: 5, Pages: e11044-e11044

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective "early" and "late" colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations.

Journal article

Cox MJ, Huang YJ, Fujimura KE, Liu JT, McKean M, Boushey HA, Segal MR, Brodie EL, Cabana MD, Lynch SVet al., 2010, Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome., PloS one, Vol: 5, Pages: e8745-e8745

Colonization of the infant gut by microorganisms over the first year of life is crucial for development of a balanced immune response. Early alterations in the gastrointestinal microbiota of neonates has been linked with subsequent development of asthma and atopy in older children. Here we describe high-resolution culture-independent analysis of stool samples from 6-month old infants fed daily supplements of Lactobacillus casei subsp. Rhamnosus (LGG) or placebo in a double-blind, randomized Trial of Infant Probiotic Supplementation (TIPS). Bacterial community composition was examined using a high-density microarray, the 16S rRNA PhyloChip, and the microbial assemblages of infants with either high or low LGG abundance were compared. Communities with high abundance of LGG exhibited promotion of phylogenetically clustered taxa including a number of other known probiotic species, and were significantly more even in their distribution of community members. Ecologically, these aspects are characteristic of communities that are more resistant to perturbation and outgrowth of pathogens. PhyloChip analysis also permitted identification of taxa negatively correlated with LGG abundance that have previously been associated with atopy, as well as those positively correlated that may prove useful alternative targets for investigation as alternative probiotic species. From these findings we hypothesize that a key mechanism for the protective effect of LGG supplementation on subsequent development of allergic disease is through promotion of a stable, even, and functionally redundant infant gastrointestinal community.

Journal article

de Menezes AB, Lockhart RJ, Cox MJ, Allison HE, McCarthy AJet al., 2008, Cellulose degradation by micromonosporas recovered from freshwater lakes and classification of these actinomycetes by DNA gyrase B gene sequencing., Applied and environmental microbiology, Vol: 74, Pages: 7080-4

A number of Micromonospora strains isolated from the water column, sediment, and cellulose baits placed in freshwater lakes were shown to be able to degrade cellulose in lake water without any addition of nutrients. A selective isolation method was also developed to demonstrate that CFU arose from both spores and hyphae that inhabit the lake environment. Gyrase B gene sequencing performed on the isolates identified a number of new centers of variation within Micromonospora, but the most actively cellulolytic strains were recovered in a single cluster that equated with the type species of the genus, M. chalcea.

Journal article

McDonald JE, Lockhart RJ, Cox MJ, Allison HE, McCarthy AJet al., 2008, Detection of novel Fibrobacter populations in landfill sites and determination of their relative abundance via quantitative PCR., Environmental microbiology, Vol: 10, Pages: 1310-9

Members of the bacterial genus Fibrobacter have long been considered important components of the anaerobic cellulolytic community in the herbivore gut, but their presence and activity in other environments is largely unknown. In this study, a specific polymerase chain reaction (PCR) primer set, targeting the 16S rRNA gene of Fibrobacter spp., was applied to community DNA from five landfill sites followed by temporal thermal gel electrophoresis (TTGE) analysis of cloned amplification products. Phylogenetic analysis of clone sequences indicated the presence of novel clusters closely related to the genus Fibrobacter. There are two named species, Fibrobacter succinogenes and F. intestinalis, and only two of the 58 sequenced clones were identified with them, and both were F. succinogenes. The clone sequences from landfill were recovered in five distinct clusters within the Fibrobacter lineage, and four of these were novel. Quantitative PCR (qPCR) assays of reverse-transcribed community RNA from landfill leachates and rumen fluid samples indicated that the abundance of Fibrobacter spp. relative to total bacteria varied from 0.2% to 40% in landfill, and 21% to 32% in the rumen, and these data demonstrate that fibrobacters can be a significant component of the microbial community in landfill ecosystems. This is the first evidence for Fibrobacter spp. outside the gut ecosystem, and as the only cultivated representatives of this group are actively cellulolytic, their diversity and abundance points to a possible role in cellulose hydrolysis in landfill, and perhaps other anaerobic environments also.

Journal article

Smith DL, Wareing BM, Fogg PCM, Riley LM, Spencer M, Cox MJ, Saunders JR, McCarthy AJ, Allison HEet al., 2007, Multilocus characterization scheme for shiga toxin-encoding bacteriophages., Applied and environmental microbiology, Vol: 73, Pages: 8032-40

Shiga toxin-producing Escherichia coli (STEC) strains are food-borne pathogens whose ability to produce Shiga toxin (Stx) is due to integration of Stx-encoding lambdoid bacteriophages. These Stx phages are both genetically and morphologically heterogeneous, and here we report the design and validation of a PCR-based multilocus typing scheme. PCR primer sets were designed for database variants of a range of key lambdoid bacteriophage genes and applied to control phages and 70 stx(+) phage preparations induced from a collection of STEC isolates. The genetic diversity residing within these populations could be described, and observations were made on the heterogeneity of individual gene targets, including the unexpected predominance of short-tailed phages with a highly conserved tail spike protein gene. Purified Stx phages can be profiled using this scheme, and the lambdoid phage-borne genes in induced STEC preparations can be identified as well as those residing in the noninducible prophage complement. The ultimate goal is to enable robust and realistically applicable epidemiological studies of Stx phages and their traits. The impact of Stx phage on STEC epidemiology is currently unknown.

Journal article

Neufeld JD, Schäfer H, Cox MJ, Boden R, McDonald IR, Murrell JCet al., 2007, Stable-isotope probing implicates Methylophaga spp and novel Gammaproteobacteria in marine methanol and methylamine metabolism., The ISME journal, Vol: 1, Pages: 480-91

The metabolism of one-carbon (C(1)) compounds in the marine environment affects global warming, seawater ecology and atmospheric chemistry. Despite their global significance, marine microorganisms that consume C(1) compounds in situ remain poorly characterized. Stable-isotope probing (SIP) is an ideal tool for linking the function and phylogeny of methylotrophic organisms by the metabolism and incorporation of stable-isotope-labelled substrates into nucleic acids. By combining DNA-SIP and time-series sampling, we characterized the organisms involved in the assimilation of methanol and methylamine in coastal sea water (Plymouth, UK). Labelled nucleic acids were analysed by denaturing gradient gel electrophoresis (DGGE) and clone libraries of 16S rRNA genes. In addition, we characterized the functional gene complement of labelled nucleic acids with an improved primer set targeting methanol dehydrogenase (mxaF) and newly designed primers for methylamine dehydrogenase (mauA). Predominant DGGE phylotypes, 16S rRNA, methanol and methylamine dehydrogenase gene sequences, and cultured isolates all implicated Methylophaga spp, moderately halophilic marine methylotrophs, in the consumption of both methanol and methylamine. Additionally, an mxaF sequence obtained from DNA extracted from sea water clustered with those detected in (13)C-DNA, suggesting a predominance of Methylophaga spp among marine methylotrophs. Unexpectedly, most predominant 16S rRNA and functional gene sequences from (13)C-DNA were clustered in distinct substrate-specific clades, with 16S rRNA genes clustering with sequences from the Gammaproteobacteria. These clades have no cultured representatives and reveal an ecological adaptation of particular uncultured methylotrophs to specific C(1) compounds in the coastal marine environment.

Journal article

Cox M, 2006, Fate of marine bacteria, NEW SCIENTIST, Vol: 191, Pages: 22-22, ISSN: 0262-4079

Journal article

McDonald IR, Kämpfer P, Topp E, Warner KL, Cox MJ, Hancock TLC, Miller LG, Larkin MJ, Ducrocq V, Coulter C, Harper DB, Murrell JC, Oremland RSet al., 2005, Aminobacter ciceronei sp. nov. and Aminobacter lissarensis sp. nov., isolated from various terrestrial environments., International journal of systematic and evolutionary microbiology, Vol: 55, Pages: 1827-32

The bacterial strains IMB-1(T) and CC495(T), which are capable of growth on methyl chloride (CH(3)Cl, chloromethane) and methyl bromide (CH(3)Br, bromomethane), were isolated from agricultural soil in California fumigated with CH(3)Br, and woodland soil in Northern Ireland, respectively. Two pesticide-/herbicide-degrading bacteria, strains ER2 and C147, were isolated from agricultural soil in Canada. Strain ER2 degrades N-methyl carbamate insecticides, and strain C147 degrades triazine herbicides widely used in agriculture. On the basis of their morphological, physiological and genotypic characteristics, these four strains are considered to represent two novel species of the genus Aminobacter, for which the names Aminobacter ciceronei sp. nov. (type strain IMB-1(T)=ATCC 202197(T)=CIP 108660(T)=CCUG 50580(T); strains ER2 and C147) and Aminobacter lissarensis sp. nov. (type strain CC495(T)=NCIMB 13798(T)=CIP 108661(T)=CCUG 50579(T)) are proposed.

Journal article

Borodina E, Cox MJ, McDonald IR, 2005, Use of DNA-stable isotope probing and functional gene probes to investigate the diversity of methyl chloride-utilizing bacteria in soil, Environmental, Vol: 7, Pages: 1318-1318

Journal article

Wilson WH, O GAT, Schroeder D, P MC, Oke J, Malin Get al., 2002, Isolation of viruses responsible for the demise of an Emiliania huxleyi bloom in the English Channel, Journal of the Marine Biological Association of the United Kingdom, Pages: 369-377

Journal article

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