Dr Brian Jones

Principal Research Fellow

contact:
Pharmacy and Biomolecular Sciences
Moulsecoomb
Brighton
BN2 4GJ

Telephone: +44 (0)1273 642098

Email: B.V.Jones@brighton.ac.uk

Research Overview

Within the broad theme of host-microbe interaction, my team is presently undertaking research at both ends of this spectrum. We utilize a wide array of molecular genetic techniques and systems-level approaches (encompassing metagenomics, metaproteomics and metabolomics) to understand host microbe-interaction from the scale of virulence mechanisms in single species, to the structure, function and health impacts of whole microbial ecosystems.

• Catheter associated UTI

Proteus mirabilis is a common cause of catheter associated urinary tract infections (CAUTI), in patients undergoing long-term bladder management. These devices are used in vast numbers in healthcare systems across the world and CAUTI are the most prevalent hospital acquired infection. P. mirabilis forms dense crystalline biofilms on catheter surfaces, which eventually block urine flow leading to complications such as pyelonephritis, septicemia and endotoxic shock.

We currently have a range of projects underway aimed at understanding the basis of P. mirabilis pathogenesis in the catheterized urinary tract, as well as developing strategies for detection and prevention of these infections. These include defining the genetic basis of biofilm formation and swarming in this organism, understanding of the regulation of gene expression during these complex processes, as well as evaluating bacteriophage based therapies for disease prevention, and aptamer based strategies for rapid point-of-care diagnosis.




Figure 1: A) Encrusted urethral catheter due to P. mirabilis biofilm formation (image courtesy of Dr D J Stickler) B-C) P. mirabilis swarming over agar surfaces, D) Real-time biophotonic analysis of gene expression during P. mirabilis swarming.


• Human gut microbiome

  The human GI tract is home to a complex microbial ecosystem composed predominantly of bacteria. This is estimated to encompass ~400-800 distinct species in the healthy adult human, and these microbes are now known to play an intimate role in our development and wellbeing. As well as undertaking a range of beneficial functions, the gut microbiome has also been implicated in a number of disease processes including colorectal cancer and inflammatory bowel disorders (IBD). A greater understanding the structure, function, and mechanisms of host-microbe interaction in this community holds the promise of significant advances in health care, including stratified or personalized medicine, and the prevention or treatment of a wide range of intestinal and metabolic disorders. My team is actively pursuing a number of projects aimed at gaining both a fundamental understanding of this ecosystem, as well as elucidating its role in the pathogenesis of colorectal cancer and IBD, and exploiting its biotechnological potential. We have also pioneered the concept and study of the human gut mobile metagenome – defined as the total pool of mobile genetic elements associated with this community, and continue to investigate the role of this flexible gene pool in gut microbiome development and function.

  
  Figure 2: Comparative metagenomic analysis of bile salt hydrolase (BSH) activity in the human gut microbiome. BSH is a key enzyme in microbial bile acid metabolism, leading to the generation of modified bile acids in the gut. Bile acids are synthesised as either glycol or tauro conjugates in the liver, and facilitate lipid absorption in the small intestine. Bile acids also have important roles as key signaling molecules regulating metabolic processes and mucosal immunity. Altered bile acids may themselves be toxic or carcinogenic and display alter binding profiles for key receptors, potentially disrupting bile acid signalling and related processes.

  A) From Jones et al 2008, PNAS 105: 13580. Function driven metagenomic analysis revealed BSH activity is distributed among all major groups of bacteria and archaea in the gut microbiome. The phylogenetic tree shows the relationship between BSH and closely revealed PVA enzymes, revealing a striking shift in substrate range toward bile acid de-conjugation among enzymes form gut associated bacteria. Green = activity against glyco-CBA and tauro-CBA; Yellow = denotes activity against tauro-CBA only. Purple = no BSH activity, Black = activity not tested. Brackets indicate clades dominated by major bacterial divisions comprising the human gut microbiota, and are generally composed of sequences from gut-associated genera. A1, A2 = Firmicutes; B = Actinobacteria; C1, C2, C3 = Bacteroidetes. Arrows show locations of archaeal sequences: 1,2) Methanobrevibacter smithii, Methanosphaera stadtmanae. 3) Methanosarcinia acetovorans. Red dots indicate sequences from human gut metagenomes. Bar represents 0.1 amino acid substitutions/site.

  B) From Jones & Ogilvie 2012, Gut, Doi: 10.1136/gutjnl-2012-302137. Comparative metgenomic analysis of BSH relative abundance profiles for major phylogenetic divisions using the MetaHIT dataset. A distinct reduction in BSH relative abundance was observed in individuals with Crohn's Disease (CD), indicating a reduced capacity of for bile acid modification in the CD gut microbiome. ACT, Actinobacteria; BACT, Bacteroidetes; FIRM, Firmicutes; TOTAL, BSH-like relative abundance in complete MetaHIT dataset regardless of phylogenetic affiliation. ALL MH, complete MetaHIT dataset, HEALTHY, Healthy individuals only, UC, individuals with ulcerative colitis only, CD, individuals with Crohn's disease only. Error bars indicate standard error of the mean (SEM). Level of significance in X2 distribution analysis: *P<0.01, **P<0.001.

Funding

Research in my laboratory is currently supported through both internal and external funding streams. External funding is presently received from:

• The Medical Research Council
• The European Union FP7 Marie Curie IAPP Scheme
• The Healthcare Infection Society
• The Royal Society
• The Society for Applied Microbiology
• The Japan Society for the Promotion of Science

Lab group

My team currently consists of 3 PhD students, 2 Postdoctoral Research Fellows, and 1 Senior technician. An additional 1-2 PhD students are expected to join my team in autumn 2012.

Recent Publications

Publications 2004- 2007

Jones B. V., Marchesi J. R. (2007) Transposon aided capture (TRACA) of plasmids resident in the human gut mobile metagenome. Nature Methods. 4: 55-61.

Jones B. V., Marchesi J. R. (2007) Accessing the mobile metagenome of the human gut microbiota. Molecular Biosystems. 3(11): 749-758.

Jones B. V., Sun F., Marchesi J. R. (2007). Using skimmed milk agar to functionally screen a gut metagenomic library for proteases may lead to false positives. Letters in Applied Microbiology. 45(4): 418-420.

Jones B. V., Mahenthiralingam E., Sabbuba, N. A., Stickler D. J. (2005) Role of swarming in the formation of crystalline Proteus mirabilis biofilms on urinary catheters. Journal of Medical Microbiology, 54: 807-813.

Jones, B. V., Young R., Mahenthiralingam E., Stickler D. J. (2004) The ultra-structure of Proteus mirabilis swarmer cell rafts, and the role of swarming in catheter-associated urinary tract infection. Infection and Immunity. 72: 3941 - 3950.

Codling, C. E., Jones B. V., Mahenthiralingam E., Russell A. D., Maillard J-Y. (2004) Identification of genes involved in the resistance of Serratia marcescens to polyquaternium-1. Journal of Antimicrobial Chemotherapy. 54: 370 – 375.

Ongoing projects

As lead investigator

• Development of methods to analyse the human gut metaproteome. In collaboration with Dr Lucas Bowler, University of Sussex.
• Response of Clostridium difficile to sub inhibitory levels of antibiotics and effect on toxin production. In collaboration with Dr M Llewelyn, BSMS.
• Role of the human gut microbiome in colorectal cancer. In collaboration with Dr C Gahan, UCC, IE; Prof J K Collins UCC, IE; and Dr J Cark, RSCH.
• Understanding the genetic basis biofilm formation in Proteus mirabilis and its contribution to catheter associated urinary tract infections
• Illuminating Biological dark matter in the human gut microbiome. In collaboration with Dr L A Ogilvie (University of Brighton).
• Elucidating mechanisms underlying host-probiotic interactions in E. coli Nissle 1917.
• Development of novel bacteriophage therapies for treatment or prevention of catheter associated infections. Coordinator of the EU FP7 BATCIC project (Bacteriophage Therapy for Catheter Infection Control) In Collaboration with Dr Cormac Gahan, UCC; Dr Paul Cotter, Teagasc, and Prof Mark Enright, Biocontrol Ltd.
• Role of novel toxin-antitoxin systems enriched in the human gut microbiome. In collaboration with Dr L A Ogilvie (University of Brighton).
• Exploring the diagnostic potential and biotechnological applications of human gut specific bacteriophage. In collaboration with Dr L A Ogilvie, Dr James Ebdon, and Dr W Macfarlane (University of Brighton).

As Collaborator

• Development of anti-Proteus DNA aptamers for diagnosis of catheter associated UTI. In collaboration with Prof K Ikebukuro, Tokyo University of Agriculture and Technology.
• Function driven metagenomic analysis of lipolytic activity in the human gut microbiome. In collaboration with Dr Paul Cotter, TFRC, Ireland.
• Discovery and characterization of novel anti-clostridial factors from the human gut microbiome. In collaboration with Prof Jay Zhu, Pennsylvania University School of Medicine, USA.
• Characterizing the antibiotic resistance pool in the human gut microbiome of intensive care patients. In collaboration with Prof Willem van Schaik, University Medical Centre Utrecht, Netherlands.

Editorial appointments

As well as undertaking regular peer review activities for a range of journals and funding agencies, I also currently act as editor for the following journals:

• Bioengineered Bugs
• Journal of Applied Microbiology
• Letters in Applied Microbiology

Teaching

I currently teach a range of microbiology subjects at level 1-3, and at M-level on a Pharmacy Masters course, and Biological/Biomedical science BSc level courses. I undertake supervision of practical laboratory based projects for M-level MPharm students, level 4 medical students (from Brighton and Sussex Medical School), and level 3 Biomedical Science students. Subjects taught include basic microbiology, pharmaceutical microbiology, preservatives and product preservation, microbial structure and function, antibiotic structure and mode of action, antibiotic resistance in clinically relevant bacteria, bacterial pathogenesis, bacterial genetics and recombination in bacteria, human gut microbiology, and gene transfer and recombination in bacteria. I previously designed and lead a module at level 1 entitled Introduction to Microbiology. Nominated for 2011 CLT Excellence in Facilitating/Empowering Learning Award.