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1.  Dengue: a continuing global threat 
Nature reviews. Microbiology  2010;8(12 0):S7-16.
Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.
PMCID: PMC4333201  PMID: 21079655
2.  Animal models for HIV/AIDS research 
Nature reviews. Microbiology  2012;10(12):852-867.
The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection.
PMCID: PMC4334372  PMID: 23154262
3.  Exploring bacterial cell biology with single-molecule tracking and super-resolution imaging 
Nature reviews. Microbiology  2014;12(1):9-22.
The ability to detect single molecules in live bacterial cells enables us to probe biological events one molecule at a time and thereby gain knowledge of the activities of intracellular molecules that remain obscure in conventional ensemble-averaged measurements. Single-molecule fluorescence tracking and super-resolution imaging are thus providing a new window into bacterial cells and facilitating the elucidation of cellular processes at an unprecedented level of sensitivity, specificity and spatial resolution. In this Review, we consider what these technologies have taught us about the bacterial cytoskeleton, nucleoid organization and the dynamic processes of transcription and translation, and we also highlight the methodological improvements that are needed to address a number of experimental challenges in the field.
PMCID: PMC3934628  PMID: 24336182
4.  Motility and more: the flagellum of Trypanosoma brucei 
Nature reviews. Microbiology  2014;12(7):505-518.
A central feature of trypanosome cell biology and life cycle is the parasite’s single flagellum, which is an essential and multifunctional organelle involved in cell propulsion, morphogenesis and cytokinesis. The flagellar membrane is also a specialized subdomain of the cell surface that harbors multiple parasite virulence factors with roles in signaling and host-parasite interactions. In this review, we discuss the structure, assembly and function of the trypanosome flagellum, including canonical roles in cell motility as well as novel and emerging roles in cell morphogenesis and host-parasite interaction.
PMCID: PMC4278896  PMID: 24931043
5.  Type VI secretion effectors: poisons with a purpose 
Nature reviews. Microbiology  2014;12(2):137-148.
The type VI secretion system (T6SS) mediates interactions between a diverse range of Gram-negative bacterial species. Recent studies have led to a drastic increase in the number of characterized T6SS effector proteins and produced a more complete and nuanced view of the adaptive significance of the system. While the system is most often implicated in antagonism, in this review we consider the case for its involvement in both antagonistic and non-antagonistic behaviors. Clarifying the roles that T6S plays in microbial communities will contribute to broader efforts to understand the importance of microbial interactions in maintaining human and environmental health, and will inform efforts to manipulate these interactions for therapeutic or environmental benefit.
PMCID: PMC4256078  PMID: 24384601
6.  Novel vaccine vectors for HIV-1 
Nature reviews. Microbiology  2014;12(11):765-771.
The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated in both preclinical and clinical trials, but, given the disappointing results of the clinical efficacy studies so far, novel vaccine approaches are needed. In this Opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for HIV-1 as two contrasting, but potentially complementary, vector approaches. Both of these vector platforms have demonstrated partial protection against stringent simian immunodeficiency virus challenges in rhesus monkeys using different immunological mechanisms.
PMCID: PMC4237164  PMID: 25296195
7.  Tackling antibiotic resistance 
Nature reviews. Microbiology  2011;9(12):894-896.
The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis.
PMCID: PMC4206945  PMID: 22048738
8.  Bordetella pertussis pathogenesis: current and future challenges 
Nature reviews. Microbiology  2014;12(4):274-288.
Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.
PMCID: PMC4205565  PMID: 24608338
9.  The Cryptic Sexual Strategies of Human Fungal Pathogens 
Nature reviews. Microbiology  2014;12(4):239-251.
PMCID: PMC4102497  PMID: 24625892
10.  The spectrum of latent tuberculosis: rethinking the goals of prophylaxis 
Nature reviews. Microbiology  2009;7(12):845-855.
Immunological tests provide evidence of latent tuberculosis in one third of the global population, more than two billion individuals. Latent tuberculosis is defined by the absence of clinical symptoms but carries a risk of subsequent progression to clinical disease, particularly in the context of co-infection with HIV. Here we discuss the biology of latent tuberculosis as part of a broad spectrum of responses that occur following infection with Mycobacterium tuberculosis, resulting in formation of a range of physiologically distinct granulomatous lesions that provide environments with differential ability to support or suppress persistence of viable bacteria. We go on to show how this model can be used to inform a rational programme to discover drugs that will be effective in the eradication of M. tuberculosis infection.
PMCID: PMC4144869  PMID: 19855401
11.  Rethinking vector immunology: the role of environmental temperature in shaping resistance 
Nature reviews. Microbiology  2012;10(12):869-876.
Recent ecological research has revealed that environmental factors can strongly affect insect immunity and influence the outcome of host–parasite interactions. To date, however, most studies examining immune function in mosquitoes have ignored environmental variability. We argue that one such environmental variable, temperature, influences both vector immunity and the parasite itself. As temperatures in the field can vary greatly from the ambient temperature in the laboratory, it will be essential to take temperature into account when studying vector immunology.
PMCID: PMC4142813  PMID: 23147703
12.  Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii 
Nature reviews. Microbiology  2013;11(8):561-573.
The agent of Q fever, Coxiella burnetii, is an obligate intracellular bacterium that causes acute and chronic infections. The study of C. burnetii pathogenesis has benefited from two recent fundamental advances: improved genetic tools and the ability to grow the bacterium in extracellular media. In this Review, we describe how these recent advances have improved our understanding of C. burnetii invasion and host cell modulation, including the formation of replication-permissive Coxiella-containing vacuoles. Furthermore, we describe the Dot/Icm (defect in organelle trafficking/intracellular multiplication) system, which is used by C. burnetii to secrete a range of effector proteins into the host cell, and we discuss the role of these effectors in remodelling the host cell.
PMCID: PMC4134018  PMID: 23797173
13.  The changing face of pathogen discovery and surveillance 
Nature reviews. Microbiology  2013;11(2):133-141.
The pace of pathogen discovery is increasing dramatically. This reflects not only factors that enable the appearance and globalization of new microbial infections but also improvements in methods for ascertainment. New molecular diagnostic platforms; investments in pathogen surveillance in wildlife, domestic animals and humans; and the advent of social media tools that mine the world wide web for clues to outbreaks of infectious disease are proving invaluable in early recognition of threats to public health. Additionally, models of microbial pathogenesis are becoming more complex, providing insights into the mechanisms by which microorganisms can contribute to chronic illnesses like cancer, peptic ulcer disease and mental illness. Here we review the contributions of each of these elements to infectious disease emergence and strategies for addressing the challenges of pathogen surveillance and discovery.
PMCID: PMC4098826  PMID: 23268232
14.  New viruses for cancer therapy: meeting clinical needs 
Nature reviews. Microbiology  2013;12(1):23-34.
Early-stage clinical trials of oncolytic virotherapy have reported the safety of several virus platforms, and viruses from three families have progressed to advanced efficacy trials. In addition, preclinical studies have established proof-of-principle for many new genetic engineering strategies. Thus, the virotherapy field now has available a diverse collection of viruses that are equipped to address unmet clinical needs owing to improved systemic administration, greater tumour specificity and enhanced oncolytic efficacy. The current key challenge for the field is to develop viruses that replicate with greater efficiency within tumours while achieving therapeutic synergy with currently available treatments.
PMCID: PMC4002503  PMID: 24292552
15.  Molecular mechanisms of varicella zoster virus pathogenesis 
Nature reviews. Microbiology  2014;12(3):197-210.
Varicella zoster virus (VZV) is the causative agent of varicella (chickenpox) and zoster (shingles). Investigating VZV pathogenesis is challenging as VZV is a human-specific virus and infection does not occur, or is highly restricted, in other species. However, the use of human tissue xenografts in mice with severe combined immunodeficiency (SCID) enables the analysis of VZV infection in differentiated human cells in their typical tissue microenvironment. Xenografts of human skin, dorsal root ganglia or foetal thymus that contains T cells can be infected with mutant viruses or in the presence of inhibitors of viral or cellular functions to assess the molecular mechanisms of VZV–host interactions. In this Review, we discuss how these models have improved our understanding of VZV pathogenesis.
PMCID: PMC4066823  PMID: 24509782
Nature reviews. Microbiology  2013;11(7):455-466.
High-throughput molecular profiling and computational biology are changing the face of virology, providing a new appreciation of the importance of the host in viral pathogenesis and offering unprecedented opportunities for better diagnostics, therapeutics and vaccines. Here, we provide a snapshot of the evolution of systems virology, from global gene expression profiling and signatures of disease outcome, to geometry-based computational methods that promise to yield novel therapeutic targets, personalized medicine and adeeper understanding of how viruses cause disease. To realize these goals, pipets and petri dishes need to join forces with the powers of mathematics and computational biology.
PMCID: PMC4028060  PMID: 23728212
17.  The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium 
Nature reviews. Microbiology  2013;11(7):443-454.
Oxic environments are hazardous. Molecular oxygen adventitiously abstracts electrons from many redox enzymes, continuously forming intracellular superoxide and hydrogen peroxide. These species can destroy the activities of metalloenzymes and the integrity of DNA, which forces organisms to protect themselves with scavenging enzymes and repair systems. Nevertheless, elevated levels of oxidants quickly poison bacteria, and both microbial competitors and hostile eukaryotic hosts exploit this vulnerability by assaulting them with peroxides or superoxide-forming antibiotics. In response, bacteria activate elegant adaptive strategies. In this Review, I summarize our current knowledge of oxidative stress in Escherichia coli, the model organism for which our understanding of damage and defence is most well-developed.
PMCID: PMC4018742  PMID: 23712352
18.  How glycan metabolism shapes the human gut microbiota 
Nature reviews. Microbiology  2012;10(5):323-335.
Symbiotic microorganisms that reside in the human intestine are adept at foraging glycans and polysaccharides, including those in dietary plants (starch, hemicellulose, pectin), animal-derived cartilage and tissue (glycosaminoglycans and N-linked glycans), and endogenous glycans from host mucus (O-linked glycans). Fluctuations in the abundance of dietary and endogenous glycans, combined with the immense chemical variation among these molecules, create a dynamic and heterogeneous environment in which gut microorganisms proliferate. In this review, we describe how glycans shape the composition of the gut microbiota over various lengths of time, the mechanisms by which individual microorganisms degrade these glycans, and potential opportunities to intentionally influence this ecosystem for better health and nutrition.
PMCID: PMC4005082  PMID: 22491358
19.  Going local: technologies for exploring bacterial microenvironments 
Nature reviews. Microbiology  2013;11(5):337-348.
Microorganisms lead social lives and use coordinated chemical and physical interactions to establish complex communities. Mechanistic insights into these interactions have revealed that there are remarkably intricate systems for coordinating microbial behaviour, but little is known about how these interactions proceed in the spatially organized communities that are found in nature. This Review describes the technologies available for spatially organizing small microbial communities and the analytical methods for characterizing the chemical environment surrounding these communities. Together, these complementary technologies have provided novel insights into the impact of spatial organization on both microbial behaviour and the development of phenotypic heterogeneity within microbial communities.
PMCID: PMC3984535  PMID: 23588251
20.  MLST revisited: the gene-by-gene approach to bacterial genomics 
Nature reviews. Microbiology  2013;11(10):728-736.
Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence-based method for identifying clonal relationships among bacteria. Today, in the whole-genome era of microbiology, the need for systematic, standardized descriptions of bacterial genotypic variation remains a priority. Here, to meet this need, we draw on the successes of MLST and 16S rRNA gene sequencing to propose a hierarchical gene-by-gene approach that reflects functional and evolutionary relationships and catalogues bacteria ‘from domain to strain’. Our gene-based typing approach using online platforms such as the Bacterial Isolate Genome Sequence Database (BIGSdb) allows the scalable organization and analysis of whole-genome sequence data.
PMCID: PMC3980634  PMID: 23979428
21.  The role of mutational robustness in RNA virus evolution 
Nature reviews. Microbiology  2013;11(5):327-336.
RNA viruses face dynamic environments and are masters at adaptation. During their short ‘lifespans’, they must surmount multiple physical, anatomical and immunological challenges. Central to their adaptative capacity is the enormous genetic diversity that characterizes RNA virus populations. Although genetic diversity increases the rate of adaptive evolution, low replication fidelity can present a risk because excess mutations can lead to population extinction. In this Review, we discuss the strategies used by RNA viruses to deal with the increased mutational load and consider how this mutational robustness might influence viral evolution and pathogenesis.
PMCID: PMC3981611  PMID: 23524517
22.  The ins and outs of hepatitis C virus entry and assembly 
Nature reviews. Microbiology  2013;11(10):688-700.
Hepatitis C virus, a major human pathogen, produces infectious virus particles with several unique features, such as an ability to interact with serum lipoproteins, a dizzyingly complicated process of virus entry, and a pathway of virus assembly and release that is closely linked to lipoprotein secretion. Here we review these unique features, with an emphasis on recent discoveries in virus particle structure, virus entry and virus particle assembly and release.
PMCID: PMC3897199  PMID: 24018384
23.  Shallow breathing: bacterial life at low O2 
Nature reviews. Microbiology  2013;11(3):205-212.
Competition for molecular oxygen (O2) among respiratory microorganisms is intense because O2 is a potent electron acceptor. This competition leads to the formation of microoxic environments wherever microorganisms congregate in aquatic, terrestrial and host-associated communities. Bacteria can harvest O2 present at low, even nanomolar, concentrations using high-affinity terminal oxidases. Here, we report the results of surveys searching for high-affinity terminal oxidase genes in sequenced bacterial genomes and shotgun metagenomes. The results indicate that bacteria with the potential to respire under microoxic conditions are phylogenetically diverse and intriguingly widespread in nature. We explore the implications of these findings by highlighting the importance of microaerobic metabolism in host-associated bacteria related to health and disease.
PMCID: PMC3969821  PMID: 23411864
24.  Reprogrammed viruses as cancer therapeutics: targeted, armed and shielded 
Nature reviews. Microbiology  2008;6(7):529-540.
Virotherapy is currently undergoing a renaissance, based on our improved understanding of virus biology and genetics and our better knowledge of many different types of cancer. Viruses can be reprogrammed into oncolytic vectors by combining three types of modification: targeting, arming and shielding. Targeting introduces multiple layers of cancer specificity and improves safety and efficacy; arming occurs through the expression of prodrug convertases and cytokines; and coating with polymers and the sequential usage of different envelopes or capsids provides shielding from the host immune response. Virus-based therapeutics are beginning to find their place in cancer clinical practice, in combination with chemotherapy and radiation.
PMCID: PMC3947522  PMID: 18552863
25.  Antimalarial Drug Discovery: Approaches and Progress towards New Medicines 
Nature reviews. Microbiology  2013;11(12):849-862.
Malaria elimination has recently been reinstated as a global health priority but current therapies seem to be insufficient for the task. Elimination efforts require new drug classes that alleviate symptoms, prevent transmission and provide a radical cure. To develop these next generation medicines, public-private partnerships are funding innovative approaches to identify compounds that target multiple parasite species at multiple stages of the parasite lifecycle. Here, we review the cell-, chemistry- and target-based approaches used to discover new drug candidates that are currently in clinical trials or undergoing preclinical testing.
PMCID: PMC3941073  PMID: 24217412

Results 1-25 (134)