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EMBO Molecular Medicine

All articles accepted from 14 August 2012 are published under the terms of the Creative Commons Attribution License.   Articles accepted before this date were published under the agreement as stated in the final article.

Cover image for Vol. 7 Issue 3

Edited By: Stefanie Dimmeler (Chief Editor), Roberto Buccione and Céline Carret (EMBO Editors)

Online ISSN: 1757-4684

Review Series: Host-pathogen interactions

How do organisms mount a protective immune response against infectious pathogens? In turn, how do pathogens subvert host defenses to successfully invade and multiply within the host? How can vaccines efficiently protect us? Pathogens have evolved numerous and clever, difficult to beat, strategies to hide or escape from the immune system. This review series focuses on these themes by providing timely analyses on microorganisms, inflammatory responses, and vaccination strategies, but also authoritative insights into these intriguing, complex and often deadly infectious diseases.



Reviews

EMBO Molecular Medicine - Emerging therapies for the treatment of hepatitis C
Christian M. Lange, Ira M. Jacobson, Charles M. Rice and Stefan Zeuzem
EMBO Mol Med, Early View
This review article thoroughly describes the more important approaches to the development of new therapies for the treatment of chronic hepatitis C. This data will be of interest for clinicians and biologists interested in infectious diseases.
EMBO Molecular Medicine - Antimicrobial peptides and gut microbiota in homeostasis and pathology
Maureen J. Ostaff, Eduard Friedrich Stange, Jan Wehkamp
EMBO Mol Med 2013, 5(10), 1465–1483
This review discusses how a balanced hostmicrobe interaction is multifactorial and depends on antimicrobial peptides, gut microbiota, innate immunity and epithelial pathways. Dysregulation of this system results in several intestinal disorders.
EMBO Molecular Medicine - Of inflammasomes and pathogens – sensing of microbes by the inflammasome
Franz Bauernfeind, Veit Hornung
EMBO Mol Med 2013, 5(6), 814–826
Inflammasomes are multiprotein platforms that recognize pathogens and play a critical role in innate immunity. This review carefully details key discoveries on how microbes are sensed by and engage inflammasomes in the host cells.
EMBO Molecular Medicine - Genetic susceptibility to Candida infections
Sanne P. Smeekens, Frank L. van de Veerdonk, Bart Jan Kullberg, Mihai G. Netea
EMBO Mol Med 2013, 5(6), 805–813
The commensal fungus Candida albicans can become pathogenic and life-threatening in immunocompromised individuals. This review focuses on the current knowledge of host genetic mutations and variants associated with an increased susceptibility to Candida infection in humans.


Further reading on host-pathogen interactions and infectious diseases

This "bridge-the-gap" discusses the helpful and harmful relationships between microbiota and its host, and provides an interesting perspective of using worms as model organism to better understand the complexity of microbiota, aging, and metabolism.
Filipe Cabreiro and David Gems
EMBO Mol Med 2013, 5(9), 1300–1310

Cerebral malaria (CM) remains a deadly yet poorly understood complication of Plasmodium falciparum infection. Here, brain microvessels cross-present P. berghei epitopes that elicit a strong CD8-response resulting in experimental CM pathogenesis.
Shanshan W. Howland, Chek Meng Poh, Sin Yee Gun, Carla Claser, Benoit Malleret, Nilabh Shastri, Florent Ginhoux, Gijsbert M. Grotenbreg and Laurent Rénia
EMBO Mol Med 2013, 5(7), 984–999

Dendritic cells actively translocate HIV-1 viruses using CCR5 as coreceptor across the intestinal epithelium during mother-to-child and sexual-anal transmission. This novel mechanism opens up avenues for new therapeutic strategies.
Mariangela Cavarelli, Chiara Foglieni, Maria Rescigno and Gabriella Scarlatti
EMBO Mol Med 2013, 5(5), 776-794
Anthony L Cunningham, Andrew Harman and Najla Nasr
EMBO Mol Med 2013, 5(5), 658-660

Gene transfer of a liver-targeted sulfamidase chimera engineered for increased secretion and blood brain barrier permeability, effectively ameliorates overall brain pathology and behavioural phenotype in treated Mucopolysaccharidosis (MPS) type IIIA mice.
Nicolina Cristina Sorrentino, Luca D'Orsi, Irene Sambri, Edoardo Nusco, Ciro Monaco, Carmine Spampanato, Elena Polishchuk, Paola Saccone, Elvira De Leonibus, Andrea Ballabio and Alessandro Fraldi
EMBO Mol Med 2013, 5(5), 675-690
William S. Sly and Carole Vogler
EMBO Mol Med 2013, 5(5), 655-657

The promise of whole genome sequencing in epidemiological investigations and the source tracking of bacterial infections is exemplified here by the discovery of potential zoonotic transmission of methicillin-resistant Staphylococcus aureus strains.
Ewan M. Harrison, Gavin K. Paterson, Matthew T.G. Holden, Jesper Larsen, Marc Stegger, Anders Rhod Larsen, Andreas Petersen, Robert L. Skov, Judit Marta Christensen, Anne Bak Zeuthen, Ole Heltberg, Simon R. Harris, Ruth N. Zadoks, Julian Parkhill, Sharon J. Peacock and Mark A. Holmes
EMBO Mol Med 2013, 5(4), 509-515
Alexander Tomasz
EMBO Mol Med 2013, 5(4), 486-487

Klebsiella rhinoscleromatis causes rhinoscleroma, a neglected infectious lung disease featuring Mikulicz cells, atypical phagocytes containing the bacteria. Maturation of inflammatory monocytes into Mikulicz cells is shown here to be IL-10-dependent.
Cindy Fevre, Ana S. Almeida, Solenne Taront, Thierry Pedron, Michel Huerre, Marie-Christine Prevost, Aurélie Kieusseian, Ana Cumano, Sylvain Brisse, Philippe J. Sansonetti and Régis Tournebize
EMBO Mol Med 2013, 5(4), 516-530

Priming in the skin with the antigens present in, or derived from, live attenuated sporozoites is shown to confer sterile protection. This provides proof-of-principle for a new anti-infection vaccination strategy based on skin-based immune responses.
Michel Obeid, Jean-François Franetich, Audrey Lorthiois, Audrey Gego, Anne Charlotte Grüner, Maurel Tefit, Claude Boucheix, Georges Snounou and Dominique Mazier
EMBO Mol Med 2013, 5(2), 250-263

The authors show that targeting NF-κB p65 may be a reasonable therapeutic strategy for asthma exacerbations, specifically addressing inflammation without compromising beneficial anti-viral immunity.
Nathan W. Bartlett, Louise Slater, Nicholas Glanville, Jennifer J. Haas, Gaetano Caramori, Paolo Casolari, Deborah L. Clarke, Simon D. Message, Julia Aniscenko, Tatiana Kebadze, Jie Zhu, Patrick Mallia, Joseph P. Mizgerd, Maria Belvisi, Alberto Papi, Sergei V. Kotenko, Sebastian L. Johnston and Michael R. Edwards
EMBO Mol Med 2012, 4(12), 1244-1260
Evangelos Andreakos
EMBO Mol Med 2012, 4(12), 1231-1233

Leishmaniasis is a fatal disease affecting mostly underdeveloped countries worldwide with a high mortality and rising drug resistance. Here, the authors show that targeting topoisomerase I of the parasite along with a Th2 to Th1 switch provides a dual mode of inhibition.
Sayan Chowdhury, Tulika Mukherjee, Rupkatha Mukhopadhyay, Budhaditya Mukherjee, Souvik Sengupta, Sharmila Chattopadhyay, Parasuraman Jaisankar, Syamal Roy and Hemanta K. Majumder
EMBO Mol Med 2012, 4(10), 1126-1143

Resistance to isoniazid, a potent anti-TB drug, is developing fast. Here, pyridomycin kills Mtb by inhibiting InhA (even in isoniazid-resistant isolates). The crystal structure provides invaluable insight for developing an effective treatment against tuberculosis.
Ruben C. Hartkoorn, Claudia Sala, João Neres, Florence Pojer, Sophie Magnet, Raju Mukherjee, Swapna Uplekar, Stefanie Boy-Röttger, Karl-Heinz Altmann and Stewart T. Cole
EMBO Mol Med 2012, 4(10), 1032-1042
Gerard D. Wright
EMBO Mol Med 2012, 4(10), 1029-1031

This position paper reviews E. coli 2011 outbreak in Europe and present discussions and conclusions from the European Academy of Microbiology on a scientific, clinical as well as political points of view.
Helge Karch, Erick Denamur, Ulrich Dobrindt, B. Brett Finlay, Regine Hengge, Ludgers Johannes, Eliora Z. Ron, Tone Tønjum, Philippe J. Sansonetti and Miguel Vicente
EMBO Mol Med 2012, 4(9), 841-848

Intestinal pathogens use the host's excessive inflammatory cytokine response to disrupt epithelial gut wall integrity and promote their tissue invasion. A glycosylated dendrimers based approach is here developed and showed effective against Shigella.
Ian Teo, Steve M. Toms, Benoit Marteyn, Teresa S. Barata, Peter Simpson, Karen A. Johnston, Pamela Schnupf, Andrea Puhar, Tracey Bell, Chris Tang, Mire Zloh, Steve Matthews, Phillip M. Rendle, Philippe J. Sansonetti and Sunil Shaunak
EMBO Mol Med 2012, 4(9), 866-881
Dermot Kelleher
EMBO Mol Med 2012, 4(9), 860-862

Clinicians can now have a way to quickly and accurately identify patients at risk of developing the most severe form of Chikungunya fever thanks to the discovery of a novel biomarker.
Yiu-Wing Kam, Fok-Moon Lum, Teck-Hui Teo, Wendy W. L. Lee, Diane Simarmata, Sumitro Harjanto, Chong-Long Chua, Yoke-Fun Chan, Jin-Kiat Wee, Angela Chow, Raymond T. P. Lin, Yee-Sin Leo, Roger Le Grand, I-Ching Sam, Joo-Chuan Tong, Pierre Roques, Karl-Heinz Wiesmüller, Laurent Rénia, Olaf Rötzschke and Lisa F. P. Ng
EMBO Mol Med 2012, 4(4), 330-343

Mycolic acids are here presented as attractive diagnostic biomarkers for tuberculosis infection. A novel mass-spectrometry-based approach proves itself reliable, sensitive and clinically relevant in an animal mouse model and patients' samples.
Guanghou Shui, Anne K. Bendt, Ignasius A. Jappar, Hui Ming Lim, Marie Laneelle, Maxime Hervé, Laura E. Via, Gek Huey Chua, Martin W. Bratschi, Siti Zarina Zainul Rahim, Ang Lay Teng Michelle, Soo-Hee Hwang, Jong-Soek Lee, Seok-Yong Eum, Hyun-Kyung Kwak, Mamadou Daffé, Véronique Dartois, Gerd Michel, Clifton E. Barry III. and Markus R. Wenk
EMBO Mol Med 2012, 4(1), 27-37

T cells are critical for controlling S. aureus infection and gradually become hyporesponsive and anergic as the infection progresses towards persistence, potentially resulting in failure of the host immune response to promote sterilizing immunity.
Christina Ziegler, Oliver Goldmann, Elias Hobeika, Robert Geffers, Georg Peters and Eva Medina
EMBO Mol Med 2011, 3(11), 652-666

Andrew M. Prentice
EMBO Mol Med 2011, 3(11), 620-622

Dorothea Orth-Höller, Magdalena Riedl and Reinhard Würzner
EMBO Mol Med 2011, 3(11), 617-619

The increased bacterial translocation from gut to tissues in mice is pathogenic at the metabolic level and leads to development of type 2 diabetes. Administration of a probiotic decreased the inflammatory status resulting in metabolic improvement.
Jacques Amar, Chantal Chabo, Aurélie Waget, Pascale Klopp, Christelle Vachoux, Luis G. Bermúdez-Humarán, Natalia Smirnova, Mathieu Bergé, Thierry Sulpice, Sampo Lahtinen, Arthur Ouwehand, Philippe Langella, Nina Rautonen, Philippe J. Sansonetti and Rémy Burcelin
EMBO Mol Med 2011, 3(9), 559-572

Yves Lévy
EMBO Mol Med 2011, 3(9), 507-509

The BCG provides only limited protection against pulmonary tuberculosis. Mutation of the secreted acid phosphatase (SapM), a molecule involved in immunomodulation, is shown to improve its vaccine potential.
Nele Festjens, Pieter Bogaert, Anjana Batni, Erica Houthuys, Evelyn Plets, Dieter Vanderschaeghe, Bram Laukens, Bob Asselbergh, Eef Parthoens, Riet De Rycke, Monique A. Willart, Peggy Jacques, Dirk Elewaut, Peter Brouckaert, Bart N. Lambrecht, Kris Huygen and Nico Callewaert
EMBO Mol Med 2011, 3(4), 222-234

S. aureus can persist within host cells for several weeks which results in bacterial phenotype switching like the altered bacterial small colony variant phenotype, along with changes in virulence and auxotrophism.
Lorena Tuchscherr, Eva Medina, Muzaffar Hussain, Wolfgang Völker, Vanessa Heitmann, Silke Niemann, Dirk Holzinger, Johannes Roth, Richard A. Proctor, Karsten Becker, Georg Peters and Bettina Löffler
EMBO Mol Med 2011, 3(3), 129-141
Christian Garzoni and William L. Kelley
EMBO Mol Med 2011, 3(3), 115-117

The study shows that the development of the human TB granuloma to caseation correlates with pathogen-mediated dysregulation of host lipid metabolism and formation of foamy macrophages, which death correspond to progression of the disease.
Mi-Jeong Kim, Helen C. Wainwright, Michael Locketz, Linda-Gail Bekker, Gabriele B. Walther, Corneli Dittrich, Annalie Visser, Wei Wang, Fong-Fu Hsu, Ursula Wiehart, Liana Tsenova, Gilla Kaplan and David G. Russell
EMBO Mol Med 2010, 2(7), 258-274

Continuous depletion of CD4+ T helper cells, key players of the adaptive immune system, is a hallmark of chronic HIV-1 infection and progression to AIDS. Chronic hyperactivation of CD4+ T cells is thought to be key to their depletion. Here, the authors show that active HIV-1 replication induces in vivo bystander activation of CD4+ T cells, which are specific for persistent herpes virus antigens.
Anna Haas, Manuela Rehr, Frederik Graw, Peter Rusert, Walter Bossart, Herbert Kuster, Alexandra Trkola, Huldrych F. Günthard and Annette Oxenius
EMBO Mol Med 2010, 2(6), 231-244

Expression of haemolytic pneumolysin is shown as a mechanism by which pneumococci evade host inflammation by inhibiting human dendritic cell maturation, inducing proinflammatory cytokines and activating the inflammasome.
Marie Littmann, Barbara Albiger, Anne Frentzen, Staffan Normark, Birgitta Henriques-Normark and Laura Plant
EMBO Mol Med 2009, 1(4), 211-222

This review discusses strategies aimed to interfere with bacterial cell-to-cell signalling via the quorum-sensing pathway to inhibit bacterial virulence and/or the development of antibiotic refractory biofilms.
Jacqueline Njoroge and Vanessa Sperandio
EMBO Mol Med 2009, 1(4), 201-210

Philippe J. Sansonetti
EMBO Mol Med 2009, 1(4), 193-194

Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal inflammatory disease. The symptoms are the result of hypercytokinaemia and organ infiltration by lymphocytes and macrophages. In this paper, the authors show that in vivo IFNγ neutralization has a dramatic curative effect on clinical and biological manifestations of experimental HLH.
Jana Pachlopnik Schmid, Chen-H. Ho, Fabrice Chrétien, Juliette M. Lefebvre, Gérard Pivert, Marie Kosco-Vilbois, Walter Ferlin, Frédéric Geissmann, Alain Fischer and Geneviève de Saint Basile
EMBO Mol Med 2009, 1(2), 112-124

Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human population, but in 90% of the cases without causing overt disease. Despite this, increasing incidence of HIV infection and emergence of drug-resistant strains means that tuberculosis is in fact an extremely serious emerging threat to global health.
Alessandra Mortellaro, Lucy Robinson and Paola Ricciardi-Castagnoli
EMBO Mol Med 2009, 1(1), 19-29

This article discusses the factors that could influence the possible pandemic potential of filoviruses and elaborates on the prerequisites for the containment of future outbreaks.
Byron E.E. Martina and Albert D.M.E. Osterhaus
EMBO Mol Med 2009, 1(1), 10-18

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