Teichoic acid biosynthesis as an antibiotic target.
Abstract The relentless spread of antibiotic-resistant pathogens makes it imperative to develop new chemotherapeutic strategies to overcome infection. The bacterial cell wall has served as a rich source for both validated and unexploited pathways that are essential for virulence and survival. Lipoteichoic acids (LTAs) and wall teichoic acids (WTAs) are cell wall polymers that play fundamental roles in Gram-positive bacterial physiology and pathogenesis, and both have been proposed as novel antibacterial targets. Here we describe recent progress toward the discovery of teichoic acid biosynthesis inhibitors and thei...
Source: Current Opinion in Microbiology - July 31, 2013 Category: Microbiology Authors: Pasquina LW, Santa Maria JP, Walker S Tags: Curr Opin Microbiol Source Type: research
Ecology and industrial microbiology.
PMID: 23910626 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - July 30, 2013 Category: Microbiology Authors: Wells JM, Langella P Tags: Curr Opin Microbiol Source Type: research
Auxiliary factors: a chink in the armor of MRSA resistance to β-lactam antibiotics.
Auxiliary factors: a chink in the armor of MRSA resistance to β-lactam antibiotics. Curr Opin Microbiol. 2013 Jul 26; Authors: Roemer T, Schneider T, Pinho MG Abstract Combination agents provide an important orthogonal approach to treat infectious diseases, particularly those caused by drug resistant pathogens. Indeed, applying a biologically 'rational' and systems-level paradigm to discover potent, selective, and synergistic agents would augment current (and arguably overly relied upon) empirical and serendipitous approaches to such discovery efforts. Here, we review the cellular mechanisms of β...
Source: Current Opinion in Microbiology - July 26, 2013 Category: Microbiology Authors: Roemer T, Schneider T, Pinho MG Tags: Curr Opin Microbiol Source Type: research
Key molecular events during host cell invasion by Apicomplexan pathogens.
Abstract The ability of Apicomplexan parasites to invade host cells is key to their survival and pathogenesis. Plasmodium and Toxoplasma parasites share common mechanisms for invasion of host cells. Secretion of microneme and rhoptry proteins, tight junction formation and assembly of an acto-myosin motor are key steps for successful invasion by both parasites. Here, we review our understanding of the molecular basis for these steps. PMID: 23895827 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - July 26, 2013 Category: Microbiology Authors: Sharma P, Chitnis CE Tags: Curr Opin Microbiol Source Type: research
Omics approaches to study host-microbiota interactions.
Abstract The intestinal microbiota has profound effects on our physiology and immune system and disturbances in the equilibrium between microbiota and host have been observed in many disorders. Here we discuss the possibilities to further our understanding of how microbiota impacts on human health and disease through the use of large-scale quantifiable tools such as transcriptomics, metagenomics and metabolomics. Reductionist models, including gnotobiotic mouse models have their place in testing hypotheses and elucidating mechanisms by which specific communities or individual species impact on host biology. Networ...
Source: Current Opinion in Microbiology - July 23, 2013 Category: Microbiology Authors: van Baarlen P, Kleerebezem M, Wells JM Tags: Curr Opin Microbiol Source Type: research
Colonic bacterial metabolites and human health.
Abstract The influence of the microbial-mammalian metabolic axis is becoming increasingly important for human health. Bacterial fermentation of carbohydrates (CHOs) and proteins produces short-chain fatty acids (SCFA) and a range of other metabolites including those from aromatic amino acid (AAA) fermentation. SCFA influence host health as energy sources and via multiple signalling mechanisms. Bacterial transformation of fibre-related phytochemicals is associated with a reduced incidence of several chronic diseases. The 'gut-liver axis' is an emerging area of study. Microbial deconjugation of xenobiotics and relea...
Source: Current Opinion in Microbiology - July 20, 2013 Category: Microbiology Authors: Russell WR, Hoyles L, Flint HJ, Dumas ME Tags: Curr Opin Microbiol Source Type: research
Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies.
dez L, Hancock RE Abstract Bacteria have evolved the ability to form multicellular, surface-adherent communities called biofilms that allow survival in hostile environments. In clinical settings, bacteria are exposed to various sources of stress, including antibiotics, nutrient limitation, anaerobiosis, heat shock, etc., which in turn trigger adaptive responses in bacterial cells. The combination of this and other defense mechanisms results in the formation of highly (adaptively) resistant multicellular structures that are recalcitrant to host immune clearance mechanisms and very difficult to eradicate with the cu...
Source: Current Opinion in Microbiology - July 20, 2013 Category: Microbiology Authors: de la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE Tags: Curr Opin Microbiol Source Type: research
Innate immunity, the constant gardener of antimicrobial defense.
PMID: 23880137 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - July 20, 2013 Category: Microbiology Authors: Schroder K, Deretic V Tags: Curr Opin Microbiol Source Type: research
PK/PD models in antibacterial development.
Abstract There is an urgent need for novel antibiotics to treat life-threatening infections caused by bacterial 'superbugs'. Validated in vitro pharmacokinetic/pharmacodynamic (PK/PD) and animal infection models have been employed to identify the most predictive PK/PD indices and serve as key tools in the antibiotic development process. The results obtained can be utilized for optimizing study designs in order to minimize the cost and duration of clinical trials. This review outlines the key in vitro PK/PD and animal infection models which have been extensively used in antibiotic discovery and development. These m...
Source: Current Opinion in Microbiology - July 18, 2013 Category: Microbiology Authors: Velkov T, Bergen PJ, Lora-Tamayo J, Landersdorfer CB, Li J Tags: Curr Opin Microbiol Source Type: research
Immunomodulatory approaches for prevention and treatment of infectious diseases.
Abstract With increasing pathogen resistance to antibiotics, population ageing, and threat of pandemics there is a strong interest in the development of new approaches for the treatment of infectious diseases. Immunomodulatory therapies are defined as interventions that target the host rather than the pathogen, modulating the immune response with the aim of disease prevention or treatment. Our growing understanding of the immune system continues to offer novel drug targets and approaches for immunomodulatory interventions. In this review we will cover prominent examples of immunomodulatory therapies already in cli...
Source: Current Opinion in Microbiology - July 17, 2013 Category: Microbiology Authors: Nijnik A Tags: Curr Opin Microbiol Source Type: research
Human intestinal metagenomics: state of the art and future.
ré J Abstract Over the last few years our understanding of human biology has undergone profound transformation. The key role of the 'world inside us', namely the gut microbiota, once considered a forgotten organ, has been revealed, with strong impact on our health and well-being. The present review highlights the most important recent findings on the role of gut microbiota and its impact on the host and raises crucial questions to be considered in future studies. PMID: 23870802 [PubMed - as supplied by publisher] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - July 16, 2013 Category: Microbiology Authors: Blottière HM, de Vos WM, Ehrlich SD, Doré J Tags: Curr Opin Microbiol Source Type: research
Probiotics from research to market: the possibilities, risks and challenges.
Pot B Abstract Probiotic foods can affect large parts of the population, while therapeutic applications have a less wide scope. While commercialization routes and regulatory requirements differ for both applications, both will need good scientific support. Today, probiotics are mainly used for gastrointestinal applications, their use can easily be extended to skin, oral and vaginal health. While most probiotics currently belong to food-grade species, the future may offer new functional microorganisms in food and pharma. This review discusses the crosstalk between probiotic producers, regulatory people, medical car...
Source: Current Opinion in Microbiology - July 15, 2013 Category: Microbiology Authors: Foligné B, Daniel C, Pot B Tags: Curr Opin Microbiol Source Type: research
Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium difficile infection.
Abstract Faecal microbiota transplantation (FMT) has been used for more than five decades to treat a variety of intestinal diseases associated with pathological imbalances within the resident microbiota, termed dysbiosis. FMT has been particularly effective for treating patients with recurrent Clostridium difficile infection who are left with few clinical options other than continued antibiotic therapy. Our increasing knowledge of the structure and function of the human intestinal microbiota and C. difficile pathogenesis has led to the understanding that FMT promotes intestinal ecological restoration and highlight...
Source: Current Opinion in Microbiology - July 15, 2013 Category: Microbiology Authors: Adamu BO, Lawley TD Tags: Curr Opin Microbiol Source Type: research
Engineering lactococci and lactobacilli for human health.
Langella P Abstract Food-grade lactic acid bacteria (LAB) are good candidates for the development of oral vectors, and are attractive alternatives to attenuated pathogens, for mucosal delivery strategies. In this review, we summarize recent results on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of this work has been based on the model LAB, Lactococcus lactis, which is suitable for the heterologous expression of therapeutic proteins. Recombinant lactococci and lactobacilli strains expressing antiproteases and antioxidant enzymes have been tested successfully for their...
Source: Current Opinion in Microbiology - July 11, 2013 Category: Microbiology Authors: Bermúdez-Humarán LG, Aubry C, Motta JP, Deraison C, Steidler L, Vergnolle N, Chatel JM, Langella P Tags: Curr Opin Microbiol Source Type: research
Virus discovery and recent insights into virus diversity in arthropods.
Abstract Recent studies on virus discovery have focused mainly on mammalian and avian viruses. Arbovirology with its long tradition of ecologically oriented investigation is now catching up, with important novel insights into the diversity of arthropod-associated viruses. Recent discoveries include taxonomically outlying viruses within the families Flaviviridae, Togaviridae, and Bunyaviridae, and even novel virus families within the order Nidovirales. However, the current focusing of studies on blood-feeding arthropods has restricted the range of arthropod hosts analyzed for viruses so far. Future investigations s...
Source: Current Opinion in Microbiology - July 11, 2013 Category: Microbiology Authors: Junglen S, Drosten C Tags: Curr Opin Microbiol Source Type: research
The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications.
Abstract There is growing interest in the ability of the intestinal microbiome to influence host function within and beyond the gastrointestinal tract. Here we review evidence of microbiome-brain interactions in mice and focus on the ability to transfer behavioral traits between mouse strains using fecal microbiota transplantation (FMT). Transplantation alters brain chemistry and behavior in recipient ex-germ free mice, raising the possibility of using FMT for disorders of the central nervous system, and prompting caution in the selection of FMT donors for conditions that may include refractory Clostridium diffici...
Source: Current Opinion in Microbiology - July 8, 2013 Category: Microbiology Authors: Collins SM, Kassam Z, Bercik P Tags: Curr Opin Microbiol Source Type: research
Faecalibacterium prausnitzii and human intestinal health.
lls J, Langella P Abstract Faecalibacterium prausnitzii is the most abundant bacterium in the human intestinal microbiota of healthy adults, representing more than 5% of the total bacterial population. Over the past five years, an increasing number of studies have clearly described the importance of this highly metabolically active commensal bacterium as a component of the healthy human microbiota. Changes in the abundance of F. prausnitzii have been linked to dysbiosis in several human disorders. Administration of F. prausnitzii strain A2-165 and its culture supernatant have been shown to protect against 2,4,6-tr...
Source: Current Opinion in Microbiology - July 3, 2013 Category: Microbiology Authors: Miquel S, Martín R, Rossi O, Bermúdez-Humarán L, Chatel J, Sokol H, Thomas M, Wells J, Langella P Tags: Curr Opin Microbiol Source Type: research
Cell surface-associated compounds of probiotic lactobacilli sustain the strain-specificity dogma.
Abstract Probiotic lactobacilli can positively impact on the health status of targeted (diseased) populations but efficacy depends strongly on the strain employed and the molecular basis for this phenomenon is poorly understood. This review discusses the current state-of-the-art in the field of molecular probiotic-host interactions, focusing on subtle strain-specific differences in the biochemical characteristics of cell surface-associated probiotic ligands and the consequences thereof for the immune responses elicited. This research is bound to enhance our understanding of strain-specificity in relation to probio...
Source: Current Opinion in Microbiology - June 28, 2013 Category: Microbiology Authors: Bron PA, Tomita S, Mercenier A, Kleerebezem M Tags: Curr Opin Microbiol Source Type: research
A life history view of mutualistic viral symbioses: quantity or quality for cooperation?
Abstract Mutualistic symbioses between viruses and their hosts do not employ a straightforward rule by viral genome characteristics, transmission mechanisms or host genotypes. In this review we propose that reproduction rates and environmental carrying capacity of hosts may play a major role in maintaining the mutualism. Depending on how host life history shifts following establishment of the symbiosis, a symbiosis can be classified as quality-selected mutualism or quantity-selected mutualism. Quality-selected mutualism is described with modified Lotka-Volterra models. Both our models and previous empirical exampl...
Source: Current Opinion in Microbiology - June 21, 2013 Category: Microbiology Authors: Bao X, Roossinck MJ Tags: Curr Opin Microbiol Source Type: research
Autophagy as an immune effector against tuberculosis.
Abstract The now well-accepted innate immunity paradigm that autophagy acts as a cell-autonomous defense against intracellular bacteria has its key origins in studies with Mycobacterium tuberculosis, an important human pathogen and a model microorganism infecting macrophages. A number of different factors have been identified that play into the anti-mycobacterial functions of autophagy, and recent in vivo studies in the mouse model of tuberculosis have uncovered additional anti-inflammatory and tissue-sparing functions of autophagy. Complementing these observations, genome wide association studies indicate a consi...
Source: Current Opinion in Microbiology - June 18, 2013 Category: Microbiology Authors: Bradfute SB, Castillo EF, Arko-Mensah J, Chauhan S, Jiang S, Mandell M, Deretic V Tags: Curr Opin Microbiol Source Type: research
Mitochondria: sensors and mediators of innate immune receptor signaling.
Abstract By integrating stress signals with inputs from other cellular organelles, eukaryotic mitochondria are dynamic sensing systems that can confer substantial impact on innate immune signaling in both health and disease. This review highlights recently discovered elements of innate immune receptor signaling (TLR, RLR, NLR, and CLR) associated with mitochondrial function and discusses the role of mitochondria in the initiation and/or manifestation of inflammatory diseases and disorders. We also highlight the role of mitochondria as therapeutic targets for inflammatory disease. PMID: 23757367 [PubMed - as s...
Source: Current Opinion in Microbiology - June 8, 2013 Category: Microbiology Authors: Cloonan SM, Choi AM Tags: Curr Opin Microbiol Source Type: research
Inhibition of human immunodeficiency virus type-1 through autophagy.
Abstract As an obligatory intracellular pathogen, human immunodeficiency virus type-1 (HIV) is dependent upon its ability to exploit host cell machinery for replication and dissemination, and to circumvent cellular processes that prevent its growth. One such intracellular process is autophagy, a component of the host defense against HIV with roles in innate immune signaling, adaptive immunity and intracellular degradation of HIV. During permissive infection, HIV down-modulates autophagy, promoting its own replication. Inducers of autophagy can overcome this suppression and inhibit HIV. This review summarizes recen...
Source: Current Opinion in Microbiology - June 5, 2013 Category: Microbiology Authors: Campbell GR, Spector SA Tags: Curr Opin Microbiol Source Type: research
Striking a balance: fungal commensalism versus pathogenesis.
Abstract The environment is suffused with nearly countless types of fungi, and our immune systems must be tuned to cope with constant exposure to them. In addition, it is becoming increasingly clear that many surfaces of our bodies are colonized with complex populations of fungi (the mycobiome) in the same way that they are colonized with complex populations of bacteria. The immune system must tolerate colonization with commensal fungi but defend against fungal invasion. Truly life-threatening fungal infections are common only when this balance is disrupted through, for example, profound immunosuppression or genet...
Source: Current Opinion in Microbiology - June 4, 2013 Category: Microbiology Authors: Iliev ID, Underhill DM Tags: Curr Opin Microbiol Source Type: research
Invasion factors of apicomplexan parasites: essential or redundant?
Abstract Apicomplexa are obligate intracellular parasites that cause several human and veterinary diseases worldwide. In contrast to most intracellular pathogens these protozoans are believed to invade a rather passive host cell in a process, that is, tightly linked to the ability of the parasites to move by gliding motility. Indeed specific inhibitors against components of the gliding machinery and the analysis of knockdown mutants demonstrate a linkage of gliding motility and invasion. Intriguingly, new data show that it is possible to block gliding motility, while host cell invasion still occurs. This suggests ...
Source: Current Opinion in Microbiology - May 30, 2013 Category: Microbiology Authors: Meissner M, Ferguson DJ, Frischknecht F Tags: Curr Opin Microbiol Source Type: research
Bacteriophage-host interaction: from splendid isolation into a messy reality.
w H Abstract In the reductionist era T-type coliphage research became one of the foundations for molecular biology. The technological progress in systems biology makes it now possible to study T-type phage-Escherichia coli interaction in the natural ecological niche, the gut of warm blooded animals. This development gives a second chance to phages as anti-microbial agents ('phage therapy'). Bacteria growing in biofilms are difficult to treat with antibiotics while many phages express naturally depolymerases which attack the polysaccharide matrix that enmesh bacteria in biofilms. Phages were already used successful...
Source: Current Opinion in Microbiology - May 28, 2013 Category: Microbiology Authors: Brüssow H Tags: Curr Opin Microbiol Source Type: research
Recent insights into apicomplexan parasite egress provide new views to a kill.
Abstract A hallmark of apicomplexan pathogens such as Plasmodium, Toxoplasma and Cryptosporidium is that they invade, replicate within, and then egress from their host cells. Egress usually results in lysis of the host cell, with deleterious consequences for the host. In the case of malaria, for example, much of the disease pathology is associated with cyclical waves of host erythrocyte destruction. This review highlights recent advances in mapping the signaling pathways that lead to egress and the parasite molecules involved in responding to and transmitting those signals. The review also discusses new findings f...
Source: Current Opinion in Microbiology - May 28, 2013 Category: Microbiology Authors: Blackman MJ, Carruthers VB Tags: Curr Opin Microbiol Source Type: research
An evolutionary perspective on the broad antiviral specificity of MxA.
Abstract Germ line encoded antiviral defenses in vertebrate cells tend to be either broadly acting factors that exploit general features of viral replication or effectors with strong pathogen preference by virtue of specific recognition of viral proteins. The Mx GTPases, however, are atypical since they have broad antiviral activity against a wide range of RNA and DNA viruses despite specifically targeting different proteins across virus families. This review presents recent advances in understanding the biochemical properties and evolution of the primate ortholog MxA, and discusses how this information begins to ...
Source: Current Opinion in Microbiology - May 28, 2013 Category: Microbiology Authors: Mitchell PS, Emerman M, Malik HS Tags: Curr Opin Microbiol Source Type: research
Protein export in malaria parasites: many membranes to cross.
Abstract The continuous multiplication of Plasmodium parasites in red blood cells leads to a rapid increase in parasite numbers and is responsible for the disease symptoms of malaria. Survival and virulence of the parasite are linked to parasite-induced changes of the host red blood cells. These alterations require export of a large number of parasite proteins that are trafficked across multiple membranes to reach the host cell. Two classes of exported proteins are known, those with a conserved Plasmodium export element (PEXEL/HT) or those without this motif (PNEPs). Recent work has revealed new aspects of the det...
Source: Current Opinion in Microbiology - May 28, 2013 Category: Microbiology Authors: Marti M, Spielmann T Tags: Curr Opin Microbiol Source Type: research
Viral pathogen discovery.
Abstract Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other b...
Source: Current Opinion in Microbiology - May 28, 2013 Category: Microbiology Authors: Chiu CY Tags: Curr Opin Microbiol Source Type: research
Inflammasome-mediated pyroptotic and apoptotic cell death, and defense against infection.
Abstract Cell death is an effective strategy to limit intracellular infections. Canonical inflammasomes, including NLRP3, NLRC4, and AIM2, recruit and activate caspase-1 in response to a range of microbial stimuli and endogenous danger signals. Caspase-1 then promotes the secretion of IL-1β and IL-18 and a rapid form of lytic programmed cell death termed pyroptosis. A second inflammatory caspase, mouse caspase-11, mediates pyroptotic death through an unknown non-canonical inflammasome system in response to cytosolic bacteria. In addition, recent work shows that inflammasomes can also recruit procaspase-8, ini...
Source: Current Opinion in Microbiology - May 23, 2013 Category: Microbiology Authors: Aachoui Y, Sagulenko V, Miao EA, Stacey KJ Tags: Curr Opin Microbiol Source Type: research
Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence.
Abstract Some RNA virus genomes bear 5'-triphosphates, which can be recognized in the cytoplasm of infected cells by host proteins that mediate anti-viral immunity. Both the innate sensor RIG-I and the interferon-induced IFIT proteins bind to 5'-triphosphate viral RNAs. RIG-I signals for induction of interferons during RNA virus infection while IFITs sequester viral RNAs to exert an anti-viral effect. Notably, the structures of these proteins reveal both similarities and differences, which are suggestive of independent evolution towards ligand binding. 5'-triphosphates, which are absent from most RNAs in the cytos...
Source: Current Opinion in Microbiology - May 23, 2013 Category: Microbiology Authors: Rehwinkel J, Reis E Sousa C Tags: Curr Opin Microbiol Source Type: research
Virome genomics: a tool for defining the human virome.
Abstract High throughput, deep sequencing assays are powerful tools for gaining insights into virus-host interactions. Sequencing assays can discover novel viruses and describe the genomes of novel and known viruses. Genomic information can predict viral proteins that can be characterized, describe important genes in the host that control infections, and evaluate gene expression of viruses and hosts during infection. Sequencing can also describe variation and evolution of viruses during replication and transmission. This review recounts some of the major advances in the studies of virus-host interactions from the ...
Source: Current Opinion in Microbiology - May 22, 2013 Category: Microbiology Authors: Wylie KM, Weinstock GM, Storch GA Tags: Curr Opin Microbiol Source Type: research
Innate receptors for adaptive immunity.
Abstract Pattern recognition receptors (PRRs) are commonly known as sensor proteins crucial for the early detection of microbial or host-derived stress signals by innate immune cells. Interestingly, some PRRs are also expressed and functional in cells of the adaptive immune system. These receptors provide lymphocytes with innate sensing abilities; for example, B cells express Toll-like receptors, which are important for the humoral response. Strikingly, certain other NOD-like receptors are not only highly expressed in adaptive immune cells, but also exert functions related specifically to adaptive immune system pa...
Source: Current Opinion in Microbiology - May 6, 2013 Category: Microbiology Authors: Michallet MC, Rota G, Maslowski K, Guarda G Tags: Curr Opin Microbiol Source Type: research
Cryptococcus neoformans constitutes an ideal model organism to unravel the contribution of cellular aging to the virulence of chronic infections.
Abstract Aging affects all organisms, from unicellular yeasts to multicellular humans. Studies in model organisms demonstrate that the pathways that mediate the two forms of aging, replicative and chronological, are highly conserved. Most studies are focused on the effect of aging on an individual cell rather than a whole population. Complex longevity regulation, however, makes aging a highly adaptive trait that is subject to natural selection. Recent studies have shed light on the potential relevance of aging in fungal pathogens, which undergo replicative aging when they expand in the host environment. Hence, pat...
Source: Current Opinion in Microbiology - April 27, 2013 Category: Microbiology Authors: Bouklas T, Fries BC Tags: Curr Opin Microbiol Source Type: research
Vesicular mechanisms of traffic of fungal molecules to the extracellular space.
Abstract Fungal cells are efficient in releasing to the extracellular space molecules that lack typical secretion signals, including cytoplasmic components. Studies developed during the last five years indicate that extracellular vesicle formation is involved in the traffic of these intracellular components to the extracellular space. The cellular origin of these vesicles, however, is still unknown. Here we review the potential mechanisms involved in formation of fungal extracellular vesicles and consequent release of fungal molecules to the outer cellular space. We also propose that these compartments can origina...
Source: Current Opinion in Microbiology - April 26, 2013 Category: Microbiology Authors: Rodrigues ML, Franzen AJ, Nimrichter L, Miranda K Tags: Curr Opin Microbiol Source Type: research
The role of 'eat-me' signals and autophagy cargo receptors in innate immunity.
Abstract Selective autophagy is an important effector mechanism of cell autonomous immunity, in particular against invasive bacterial species. Anti-bacterial autophagy is activated by rupture of bacteria-containing vacuoles and exposure of bacteria to the cytosol. The autophagy cargo receptors p62, NDP52 and Optineurin detect incoming bacteria that have become associated with specific 'eat-me' signals such as Galectin-8 and poly-ubiquitin and feed them into the autophagy pathway via interactions with phagophore-associated ATG8-like proteins. Here we review recent progress in the field regarding the origin of bacte...
Source: Current Opinion in Microbiology - April 23, 2013 Category: Microbiology Authors: Boyle KB, Randow F Tags: Curr Opin Microbiol Source Type: research
Fungal glycan interactions with epithelial cells in allergic airway disease.
Abstract Human exposure to fungi results in a wide range of health outcomes, from invasive disease or allergy to immune tolerance. Inhaled fungi contact airway epithelial cells as an early event, and this host:fungal interaction can shape the eventual immunological outcome. Emerging evidence points to exposure to fungal cell wall carbohydrates in the development of allergic airway disease. Herein, we describe determinants of fungal allergenicity, and review the responses of airway epithelial cells to fungal carbohydrates. A greater understanding of the recognition of and response to fungal carbohydrates by airway ...
Source: Current Opinion in Microbiology - April 17, 2013 Category: Microbiology Authors: Roy RM, Klein BS Tags: Curr Opin Microbiol Source Type: research
Fungal cell wall dynamics and infection site microenvironments: signal integration and infection outcome.
Abstract Upon entrance into the host, fungi encounter a myriad of host effector products and microenvironments that they sense and adapt to for survival. Alterations of the structure and composition of the cell wall is a major fungal adaptation mechanism to evade these environments. Here we discuss recent findings of host-microenvironmental induced fungal cell wall changes, including structure, composition, and protein content, and their effects on host immune responses. A take home message from these recent studies is an emerging understanding of how integration of multiple signals, of both fungal and host respon...
Source: Current Opinion in Microbiology - April 15, 2013 Category: Microbiology Authors: Shepardson KM, Cramer RA Tags: Curr Opin Microbiol Source Type: research
The fungal Achilles' heel: targeting Hsp90 to cripple fungal pathogens.
Abstract There is a pressing need for new therapeutic strategies for life-threatening fungal infections. Targeting the molecular chaperone Hsp90 has emerged as a promising approach to cripple fungal pathogens, thereby enhancing antifungal efficacy, impairing the evolution of drug resistance, and rendering resistant pathogens responsive to treatment. Hsp90 inhibitors in clinical development for cancer may be repurposed for some therapeutic applications, though others require fungal selective Hsp90 inhibitors or alternative strategies to inhibit the chaperone machinery. Novel targets include upstream regulators of H...
Source: Current Opinion in Microbiology - April 12, 2013 Category: Microbiology Authors: Cowen LE Tags: Curr Opin Microbiol Source Type: research
Titan cells in Cryptococcus neoformans: cells with a giant impact.
Abstract Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100μm in cell body diameter, in contrast to typical size cells of 5-7μm. These titan cells pose a problem for the host because they contribute to...
Source: Current Opinion in Microbiology - April 12, 2013 Category: Microbiology Authors: Zaragoza O, Nielsen K Tags: Curr Opin Microbiol Source Type: research
Candida albicans biofilms: building a heterogeneous, drug-tolerant environment.
Abstract Fungi are able to form biofilms on medical implants, causing serious infections. A better understanding of fungal biofilm formation is necessary to develop tools for detection or prevention and to identify new antifungal strategies. This review explores recent advances in the characterization at the molecular level of fungal biofilms, especially those formed by the yeast Candida albicans: the identification of complex transcriptional networks that control their formation; the pivotal role of the extracellular matrix in biofilm antifungal tolerance; and the knowledge gained on the physiology of biofilm cel...
Source: Current Opinion in Microbiology - April 5, 2013 Category: Microbiology Authors: Bonhomme J, d'Enfert C Tags: Curr Opin Microbiol Source Type: research
RNA polymerase and the ribosome: the close relationship.
Abstract In bacteria transcription and translation are linked in time and space. When coupled to RNA polymerase (RNAP), the translating ribosome ensures transcriptional processivity by preventing RNAP backtracking. Recent advances in the field have characterized important linker proteins that bridge the gap between transcription and translation: In particular, the NusE(S10):NusG complex and the NusG homolog, RfaH. The direct link between the moving ribosome and RNAP provides a basis for maintaining genomic integrity while enabling efficient transcription and timely translation of various genes within the bacterial...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: McGary K, Nudler E Tags: Curr Opin Microbiol Source Type: research
Entering the era of bacterial epigenomics with single molecule real time DNA sequencing.
Abstract DNA modifications, such as methylation guide numerous critical biological processes, yet epigenetic information has not routinely been collected as part of DNA sequence analyses. Recently, the development of single molecule real time (SMRT) DNA sequencing has enabled detection of modified nucleotides (e.g. 6mA, 4mC, 5mC) in parallel with acquisition of primary sequence data, based on analysis of the kinetics of DNA synthesis reactions. In bacteria, genome-wide mapping of methylated and unmethylated loci is now feasible. This technological advance sets the stage for comprehensive, mechanistic assessment of...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Davis BM, Chao MC, Waldor MK Tags: Curr Opin Microbiol Source Type: research
Signaling diversity and evolution of extracytoplasmic function (ECF) σ factors.
Signaling diversity and evolution of extracytoplasmic function (ECF) σ factors. Curr Opin Microbiol. 2013 Apr;16(2):148-55 Authors: Mascher T Abstract Extracytoplasmic function σ factors (ECFs) represent a fundamental and widely distributed principle of bacterial signal transduction that connects the perception of a stimulus (input) with the induction of an appropriate set of genes (output). In recent years, comparative genomics analyses have not only allowed a systematic and functional classification of ECFs but also indicated the presence of numerous novel and widely conserved mechanisms of E...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Mascher T Tags: Curr Opin Microbiol Source Type: research
Lost after translation: post-translational modifications by bacterial type III effectors.
Abstract Many Gram-negative bacterial pathogens use the type III secretion system to deliver effector proteins into host cells. These effectors use various mechanisms to exploit host processes to the advantage of the pathogen. A large group of effectors use post-translational modifications, either reversible or irreversible, to manipulate host proteins, and while most of these mechanisms mimic eukaryotic activities, others appear to be unique biochemical functions. Deciphering such mechanisms and identifying the host targets of these effectors sheds light on eukaryotic signaling pathways and immune responses. ...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Salomon D, Orth K Tags: Curr Opin Microbiol Source Type: research
Heterogeneity of intracellular replication of bacterial pathogens.
Abstract Intracellular growth of bacterial pathogens is usually measured at the whole population level, which masks potential cell-to-cell variation. More direct measurements of replication using microscopy and Flow Cytometry have revealed extensive heterogeneity among populations of intracellular bacteria. Heterogeneity could result from differential exposure to nutritional deprivation and host cell antimicrobial activities, as well as variability in production or efficacy of virulence molecules. Furthermore, bacteria have evolved specific mechanisms to generate epigenetic variation. These include unequal partiti...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Helaine S, Holden DW Tags: Curr Opin Microbiol Source Type: research
dUTPases, the unexplored family of signalling molecules.
e;s MÁ, Marina A Abstract Deciphering the molecular mechanisms that control relevant cellular processes is of utmost importance to understand how viruses, prokaryotic and eukaryotic cells work. The diversity of living organisms suggests that there are novel regulators still to be discovered, which may uncover new regulatory paradigms. dUTPases (Duts) are assumed to be ubiquitous enzymes regulating cellular dUTP levels to prevent misincorporation of uracil into DNA. Recently however, Duts have been involved in the control of several relevant cellular processes, including transfer of mobile genetic elements, ...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Penadés JR, Donderis J, García-Caballer M, Tormo-Más MÁ, Marina A Tags: Curr Opin Microbiol Source Type: research
Disruption of the gut microbiome as a risk factor for microbial infections.
Abstract The discovery that microorganisms can be etiologic agents of disease has driven clinical, research and public health efforts to reduce exposure to bacteria. However, despite extensive campaigns to eradicate pathogens (via antibiotics, vaccinations, hygiene, sanitation, etc.), the incidence and/or severity of multiple immune-mediated diseases including, paradoxically, infectious disease have increased in recent decades. We now appreciate that most microbes in our environment are not pathogenic, and that many human-associated bacteria are symbiotic or beneficial. Notably, recent examples have emerged reveal...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Khosravi A, Mazmanian SK Tags: Curr Opin Microbiol Source Type: research
Beyond the cytoskeleton: mesoscale assemblies and their function in spatial organization.
Abstract Recent studies have identified a growing number of mesoscale protein assemblies in both bacterial and eukaryotic cells. Traditionally, these polymeric assemblies are thought to provide structural support for the cell and thus have been classified as the cytoskeleton. However a new class of macromolecular structure is emerging as an organizer of cellular processes that occur on scales hundreds of times larger than a single protein. We propose two types of self-assembling structures, dynamic globules and crystalline scaffolds, and suggest they provide a means to achieve cell-scale order. We discuss general ...
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Wilson MZ, Gitai Z Tags: Curr Opin Microbiol Source Type: research
Bacterial regulatory mechanisms: the gene and beyond.
PMID: 23623149 [PubMed - in process] (Source: Current Opinion in Microbiology)
Source: Current Opinion in Microbiology - April 1, 2013 Category: Microbiology Authors: Bassler B, Vogel J Tags: Curr Opin Microbiol Source Type: research