Future MICROBIOLOGY Abstract Book Senior Editors: A Calderone, Georgetown University, WA, USA Brett Finlay, University of British Columbia, Canada

Microbiology has inevitably been impacted by the genomic revolution, with the first microbial genome sequencing project, that of Haemophilus influenzae, being completed in 1995. While microbes are thought to make up approximately 60% of the earth’s biomass, less than 1% of them have been characterized so far. Research into the extreme diversity of microbial organisms will lead to the elucidation of new biologic pathways and gene products, and thus potential therapeutic strategies to combat or prevent infection. The development of more accurate and rapid diagnostic techniques is also crucial to facilitate the rapid dissemination of suitable control methods in the case of novel or re-emerging pathogens. Resistance to current treatment strategies is set to continue and will become a greater problem in the future unless new treatment methods are developed.

Future Microbiology is a peer-reviewed journal that delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this increasingly important and INDEXING vast area of research. • Biobase This document includes a summary of some recent top articles, all • BIOSIS Previews IMPACT FACTOR of which are free to read in full • BIOSIS Reviews Reports and Meetings on the journal’s website (http:// • Biotechnology Citation Index® 3.637 www.futuremedicine.com/loi/ • CAB abstracts fmb). For more information, to (2015) ask a question, or to submit an • Chemical Abstracts article proposal, please e-mail • Current Awareness in Biological Sciences (CABS) the journal’s Commissioning • EMBASE/Excerpta Medica Editor’s Frances Adlam (f.adlam@ • EMBiology futuremedicine.com) or Hannah • Journal Citation Reports/Science Edition® Makin (h.makin@futuremedicine. com). • MEDLINE/Index Medicus • Science Citation Index Expanded™ (SciSearch®) • Scopus®

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01 The human gut microbiota is a metabolic organ that is determined by a dynamic process of selection and competition. Age, dietary habits and geographical origin of people have an important impact Review on the intestinal microbiota. The role of the microbiota is still largely The relationship between gut microbiota and unknown, but the bacteria of the gut flora do contribute enzymes that weight gain in humans are absent in humans and play an essential role in the catabolism of dietary fibers. Germ-free mice provide a complementary approach for 1 1 Emmanouil Angelakis , Fabrice Armougom , Matthieu characterizing the properties of the human gut microbiota. Recently, Million1 & Didier Raoult1 microbial changes in the human gut were proposed to be one of the 1Unité des Rickettsies, URMITE -CNRS UMR 6236 IRD 198, IFR 48, Faculté de Médecine, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille Cedex possible causes of obesity. This review summarizes the latest research on 05, France the association between microbial ecology and host weight. Future Microbiology 7(1), 91–109 (2012). www.futuremedicine.com/doi/full/10.2217/fmb.11.142 Altmetric: 29 Usage: 10,491

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02 and future challenges in the study of antibiotic resistance through metagenomic approaches. Review Altmetric: 18 Usage: 7455 Phage cocktails and the future of phage therapy Benjamin K Chan1, Stephen T Abedon2 & Catherine Loc-Carrillo3,4 04 1Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA 2Department of Microbiology, Ohio State University, Mansfield, OH, USA 3Department of Orthopedics, University of Utah, Salt Lake City, UT, USA Perspective 4Department of Veterans Affairs, Health Care System, Salt Lake City, UT, USA Future Microbiology 8(6), 769–783 (2013). Nucleic acids as viability markers for bacteria www.futuremedicine.com/doi/full/10.2217/fmb.13.47 detection using molecular tools Claire Cenciarini-Borde1,2, Sophie Courtois1& Viruses of bacteria, known as bacteriophages or phages, were Bernard La Scola2 discovered nearly 100 years ago. Their potential as antibacterial agents 1CIRSEE (Centre International de Recherche Sur l’Eau et l’Environnement) – Suez Environment, 38 Rue Du Président Wilson 78230 Le Pecq, France was appreciated almost immediately, with the first ‘phage therapy’ 2URMITE, CNRS-IRD UMR 6236, Université de la Méditerranée, Faculté de Médecine, trials predating Fleming’s discovery of penicillin by approximately a 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France decade. In this review, we consider phage therapy that can be used for Future Microbiology 4(1), 45–64 (2009). treating bacterial infections in humans, domestic animals and even www.futuremedicine.com/doi/full/10.2217/17460913.4.1.45 biocontrol in foods. Following an overview of the topic, we explore the common practice – both experimental and, in certain regions A large set of nucleic acid detection methods with good sensitivity and of the world, clinical – of mixing therapeutic phages into cocktails specificity are now available for the detection of pathogens in clinical, consisting of multiple virus types. We conclude with a discussion of food and environmental samples. Given increasing demand, many the commercial and medical context of phage cocktails as therapeutic efforts have been made to combine these methods to assess viability. agents. In comparing off-the-shelf versus custom approaches, we Genomic DNA PCR amplification has been shown to be inappropriate consider the merits of a middle ground, which we deem ‘modifiable’. for distinguishing viable from dead bacteria owing to DNA stability. Finally, we explore a regulatory framework for such an approach based Many authors have tried to bypass this difficulty by switching to RNA on an influenza vaccine model. amplification methods such as reverse transcription-PCR and nucleic acid sequence-based amplification. More recently, researchers have Altmetric: 2 Usage: 7564 developed methods combining specific sample pretreatment with nucleic acid detection methods, notably ethidium or propidium monoazide pretreatment coupled with PCR DNA detection or direct viable count methods and subsequent fluorescent in situ hybridization of 16S rRNA. 03 This review evaluates the performance of these different methods for viability assessment. Review Usage: 7803 Insights into antibiotic resistance through metagenomic approaches

1 1,2 Robert Schmieder & Robert Edwards 05 1Computational Science Research Center & Department of Computer Science, San Diego State University, San Diego, CA 92182, USA 2Mathematics and Computer Science Division, Argonne National Laboratory, 9700 South Cass Ave, Argonne, IL 60439, USA Review Future Microbiology 7(1), 73–89 (2012). Tuberculous meningitis in adults: a review www.futuremedicine.com/doi/full/10.2217/fmb.11.135 of a decade of developments focusing on prognostic factors for outcome The consequences of bacterial infections have been curtailed by the introduction of a wide range of antibiotics. However, infections Flavia Brancusi1, Jeremy Farrar2 & Dorothee Heemskerk2 continue to be a leading cause of mortality, in part due to the evolution 1Princeton University, Princeton, NJ, USA 2Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam and acquisition of antibiotic-resistance genes. Antibiotic misuse Future Microbiology 7(9), 1101–1116 (2012). and overprescription have created a driving force influencing the selection of resistance. Despite the problem of antibiotic resistance in www.futuremedicine.com/doi/full/10.2217/fmb.12.86 infectious bacteria, little is known about the diversity, distribution and origins of resistance genes, especially for the unculturable majority of Tuberculous meningitis (TBM) is the most severe form of TB. Despite environmental bacteria. Functional and sequence-based metagenomics treatment, mortality and long-term disability remain unacceptably high. have been used for the discovery of novel resistance determinants and Prevention, early recognition, diagnosis and treatment are fundamental the improved understanding of antibiotic-resistance mechanisms in to improving outcomes. However, an effective vaccine remains elusive, clinical and natural environments. This review discusses recent findings initial symptoms are nonspecific, and sensitive diagnostic tests are

2 www.futuremedicine.com Future Abstract Book MICROBIOLOGY not available. There has been progress in our understanding of the 07 immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and Review clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on Postgenomic strategies in antibacterial drug presentation, seizures, stroke, cranial nerve involvement, cerebrospinal discovery fluid cell count and lactate levels, hyponatreamia and coinfection with 1 2 HIV are all found to be important prognostic factors for outcome. Heike Brötz-Oesterhelt & Peter Sass 1AiCuris, Wuppertal, Germany, Institute for Pharmaceutical Biology, University of Pathogen lineage (Beijing genotype) and host genetics (polymorphisms Duesseldorf, Universitätsstrasse 1, Building 26.23.U1, Germany in TLR2, TIRAP and LTA4H genes) can influence susceptibility to 2Institute of Medical Microbiology, Immunology & Parasitology, Pharmaceutical Microbiology Section, University of Bonn, Germany TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic Future Microbiology 5(10), 1553–1579 (2010). tests, novel insights into pathogenesis and an increasing evidence base www.futuremedicine.com/doi/full/10.2217/fmb.10.119 for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines. During the last decade the field of antibacterial drug discovery has changed in many aspects including bacterial organisms of primary interest, discovery strategies applied and pharmaceutical companies Altmetric: 1 Usage: 4495 involved. Target-based high-throughput screening had been disappointingly unsuccessful for antibiotic research. Understanding of this lack of success has increased substantially and the lessons learned 06 refer to characteristics of targets, screening libraries and screening strategies. The ‘genomics’ approach was replaced by a diverse array of discovery strategies, for example, searching for new natural product Review leads among previously abandoned compounds or new microbial Virulence factors involved in the pathogenesis sources, screening for synthetic inhibitors by targeted approaches of the infection caused by the swine pathogen including structure-based design and analyses of focused libraries and designing resistance-breaking properties into antibiotics of established and zoonotic agent Streptococcus suis classes. Furthermore, alternative treatment options are being pursued Nahuel Fittipaldi1, Mariela Segura1, Daniel Grenier2 & including anti-virulence strategies and immunotherapeutic approaches. 1 Marcelo Gottschalk This article summarizes the lessons learned from the genomics era and 1 Groupe de Recherche sur les Maladies Infectieuses du Porc & Centre de Recherche describes discovery strategies resulting from that knowledge. en Infectiologie Porcine, Faculté de médecine vétérinaire, Université de Montréal, 3200 rue Sicotte, CP5000, St-Hyacinthe, Quebec, J2S 7C6, Canada 2Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec, Canada Usage: 3895 Future Microbiology 7(2), 259–279 (2012). www.futuremedicine.com/doi/full/10.2217/fmb.11.149

08 Streptococcus suis is a major swine pathogen responsible for important economic losses to the swine industry worldwide. It is also an emerging zoonotic agent of meningitis and streptococcal toxic shock-like Editorial syndrome. Since the recent recognition of the high prevalence of S. suis Ebolavirus: a brief review of novel therapeutic human disease in southeast and east Asia, the interest of the scientific community in this pathogen has significantly increased. In the last few targets years, as a direct consequence of these intensified research efforts, large Andrew S Kondratowicz1 & Wendy J Maury1 amounts of data on putative virulence factors have appeared in the 1Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa literature. Although the presence of some proposed virulence factors City, IA, USA does not necessarily define a S. suis strain as being virulent, several cell- Future Microbiology 7(1), 1–4 (2012). associated or secreted factors are clearly important for the pathogenesis www.futuremedicine.com/doi/full/10.2217/fmb.11.110 of the S. suis infection. In order to cause disease, S. suis must colonize the host, breach epithelial barriers, reach and survive in the bloodstream, Ebolavirus (EBOV) and Marburgvirus (MARV) are members of the invade different organs, and cause exaggerated inflammation. In this family Filoviridae and contain a single-stranded, negative sense ~19 kb review, we discuss the potential contribution of different described S. RNA genome. There is a single species of MARV, whereas there are suis virulence factors at each step of the pathogenesis of the infection. five known species of EBOV: Zaire EBOV, Reston EBOV, Ivory Coast Finally, we briefly discuss other described virulence factors, virulence EBOV, Sudan EBOV and Bundibugyo EBOV. While Reston EBOV factor candidates and virulence markers for which a precise role at does not cause disease in humans, the other four species cause Ebola specific steps of the pathogenesis of the S. suis infection has not yet hemorrhagic fever (EHF), with human mortality rates between 40– been clearly established. 90% and no vaccines or antivirals are currently available. As disease symptoms are thought to be caused by both replication of the virus and host immune responses, promising future therapies logically would Altmetric: 1 Usage: 4208 focus on reducing virus load and/or enhancing productive immune responses.

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Altmetric: 8 Usage: 3895 Editorial Could fecal microbiota transplantation cure 09 all Clostridium difficile infections? Thomas J Borody1, Debra Peattie2 & Amit Kapur3 Review 1Centre for Digestive Diseases, Level ½29 Great North Road, Five Dock, New South Wales 2046, Australia Polio vaccination: past, present and future 2Pleiades Advisors, 13 Oak Meadow Road, Lincoln, MA 01773, USA 3Prince of Wales Hospital, Randwick, New South Wales 2031, Australia Ananda S Bandyopadhyay1, Julie Garon2, Katherine Seib2 Future Microbiology 9(1), 1–3 (2014). & Walter A Orenstein2 www.futuremedicine.com/doi/full/10.2217/fmb.13.146 1Bill & Melinda Gates Foundation, 1432 Elliott Ave W, Seattle, WA 98119, USA 2Division of Infectious Diseases, Emory University School of Medicine, 1462 Clifton Road, Room 446, Atlanta, GA 30322, USA In its current form, fecal microbiota transplantation (FMT) is a Future Microbiology 10(5), 791–808 (2015). novel medical therapy. Intriguingly, however, early Chinese writings www.futuremedicine.com/doi/full/10.2217/fmb.15.19 reveal that it was practiced centuries ago in its crudest form using ingested fecal material to treat gastrointestinal ailments such as Live attenuated oral polio vaccine (OPV) and inactivated polio vaccine food poisoning and severe diarrhea. As we discuss here, this ancient (IPV) are the tools being used to achieve eradication of wild polio medical practice may now be coming ‘full circle‘. In 1958, Eiseman virus. Because OPV can rarely cause paralysis and generate revertant and colleagues documented the first modern report of FMT to treat polio strains, IPV will have to replace OPV after eradication of pseudomembranous colitis due to suspected Clostridium difficile wild polio virus is certified to sustain eradication of all polioviruses. infection (CDI). The authors detailed an “immediate and dramatic However, uncertainties remain related to IPV’s ability to induce response” following FMT and suggested that “this simple yet rational intestinal immunity in populations where fecal–oral transmission therapy method should be given more extensive clinical evaluation”. is predominant. Although substantial effectiveness and safety data Although C. difficile was not described until 1978, the Eiseman et al. exist on the use and delivery of OPV and IPV, several new research report and several others that followed almost certainly described initiatives are currently underway to fill specific knowledge gaps to treatments for what we now know to be CDI colitis. inform future vaccination policies that would assure polio is eradicated and eradication is maintained. Usage: 3035

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