Trends in microbiology

Publication Date: PMID:
Authors:
Journal:

post to: CiteULike

How academic labs can approach the drug discovery process as a way to synergize with big pharma.

Publication Date: 2013 Jun PMID: 23731493
Authors: Loregian, A. - Palu, G.
Journal: Trends Microbiol

While the pharmaceutical industry is facing highly challenging times, the academic drug discovery sector has the potential to contribute meaningfully to the discovery of novel drug targets and to the development of new mode-of-action therapeutics against a range of diseases, including rare and neglected diseases.

post to: CiteULike

Innate immune detection of microbial nucleic acids.

Publication Date: 2013 May 29 PMID: 23726320
Authors: Gurtler, C. - Bowie, A. G.
Journal: Trends Microbiol

Detection of pathogen-derived nucleic acids by pattern recognition receptors (PRRs) is essential for the host to mount an appropriate immune response, which for viruses involves the induction of type I interferons (IFNs). By contrast, inappropriate activation of PRRs by self nucleic acids can lead to autoimmunity. Recent developments in PRR research have uncovered important new molecular details as to how Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) distinguish pathogen from self RNA, while the discovery of cytosolic DNA sensing pathways for IFN induction has revealed completely new innate signaling mechanisms, and also questions how innate immunity discriminates between self and non-self DNA, if at all.

post to: CiteULike

Lose the battle to win the war: bacterial strategies for evading host inflammasome activation.

Publication Date: 2013 May 24 PMID: 23712018
Authors: Higa, N. - Toma, C. - Nohara, T. - Nakasone, N. - Takaesu, G. - Suzuki, T.
Journal: Trends Microbiol

The inflammasome is composed of nucleotide-binding, oligomerization domain (NOD)-like receptor (NLR) proteins, and leads to caspase-1 activation and subsequent secretion of the proinflammatory cytokines interleukin 1beta (IL-1beta) and interleukin-18 (IL-18). After certain pathogenic bacteria infect host cells, such as macrophages, NLR-mediated inflammasome activation is triggered to form part of the host defenses against the invading pathogens. However, recent evidence has shown that bacteria have strategies for evading inflammasome activation in host cells. In this review, we focus on NLR-mediated inflammasome activation and bacterial evasion of the inflammasome as part of the battle between the host defenses and pathogens.

post to: CiteULike

Probiotic strategies for treatment of respiratory diseases.

Publication Date: 2013 May 23 PMID: 23707554
Authors: Nagalingam, N. A. - Cope, E. K. - Lynch, S. V.
Journal: Trends Microbiol

Recent advances in next-generation sequencing and phylogenetic microarray technologies have identified diverse, niche-specific microbial communities that comprise the human superorganism. Mucosal microbiome perturbation is a prominent feature of an increasing number of chronic inflammatory disorders, including respiratory diseases, and efforts are now focused on identifying novel microbe-based strategies to treat or manage these conditions. Considering the evidence for niche-specificity and the diversity of function that human microbial communities afford, the range of therapeutic species used to date in probiotic supplements is strikingly narrow and is limited to species typically of gastrointestinal origin. Although the field is still relatively nascent, the potential for identifying novel microbe-based therapeutics in the human microbiome is great. This article focuses primarily on the respiratory tract, its associated microbiome, potential interactions with the gastrointestinal microbiota, and the possibilities for microbiome-manipulation strategies in the treatment and prevention of respiratory disease.

post to: CiteULike

Programmed cell death in bacteria and implications for antibiotic therapy.

Publication Date: 2013 Jun PMID: 23684151
Authors: Tanouchi, Y. - Lee, A. J. - Meredith, H. - You, L.
Journal: Trends Microbiol

It is now well appreciated that programmed cell death (PCD) plays critical roles in the life cycle of diverse bacterial species. It is an apparently paradoxical behavior as it does not benefit the cells undergoing PCD. However, growing evidence suggests that PCD can be 'altruistic': the dead cells may directly or indirectly benefit survivors through generation of public goods. This property provides a potential explanation on how PCD can evolve as an extreme form of cooperation, although many questions remain to be addressed. From another perspective, as PCD plays a critical role in bacterial pathogenesis, it has been proposed as a potential target for new antibacterial therapy. To this end, understanding the population and evolutionary dynamics resulting from PCD and public goods production may be a key to the success of designing effective antibiotic treatment.

post to: CiteULike

Potential of protein kinase inhibitors for treating herpesvirus-associated disease.

Publication Date: 2013 Jun PMID: 23608036
Authors: Li, R. - Hayward, S. D.
Journal: Trends Microbiol

Herpesviruses are ubiquitous human pathogens that establish lifelong persistent infections. Clinical manifestations range from mild self-limiting outbreaks such as childhood rashes and cold sores to the more severe and life-threatening outcomes of disseminated infection, encephalitis, and cancer. Nucleoside analog drugs that target viral DNA replication provide the primary means of treatment. However, extended use of these drugs can result in selection for drug-resistant strains, particularly in immunocompromised patients. In this review we will present recent observations about the participation of cellular protein kinases in herpesvirus biology and discuss the potential for targeting these protein kinases as well as the herpesvirus-encoded protein kinases as an anti-herpesvirus therapeutic strategy.

post to: CiteULike

Interpreting infective microbiota: the importance of an ecological perspective.

Publication Date: 2013 Jun PMID: 23598051
Authors: Rogers, G. B. - Hoffman, L. R. - Carroll, M. P. - Bruce, K. D.
Journal: Trends Microbiol

Complex microbiota are being reported increasingly across a range of chronic infections, including those of the cystic fibrosis airways. Such diversity fits poorly into classical models of sterile tissue infections, which generally involve one species, and where microbe-outcome associations usually imply causality. It has been suggested that microbiota at sites of infection could represent pathogenic entities, analogous to individual species. We argue that our ability to identify causality in microbiota-disease associations is, however, inherently confounded. Although particular microbiota may be associated with clinical outcomes, niche characteristics at sites of infection will shape microbiota composition through exerting selective pressures. Here, we suggest that ecological theory can inform clinical understanding.

post to: CiteULike

Daily battle against body odor: towards the activity of the axillary microbiota.

Publication Date: 2013 Jun PMID: 23566668
Authors: Fredrich, E. - Barzantny, H. - Brune, I. - Tauch, A.
Journal: Trends Microbiol

The microbial community of the human axilla plays a key role in the formation of axillary odor by biotransformation of odorless natural secretions into volatile odorous molecules. Culture-based microbiological and biochemical studies have allowed the characterization of the axillary microbiota, but the advent of next-generation culture-independent DNA sequencing approaches has provided an unprecedented depth of data regarding the taxonomic composition of the axillary microbiota and intra- and interindividual variation. However, the physiological activity of the microbiota of an individual and its variation under different environmental conditions remains largely unknown. Thus, metatranscriptomics represents a promising technique to identify specific metabolic activities in the axillary microbiota linked to individual differences in body odor.

post to: CiteULike

Mechanisms of endospore inactivation under high pressure.

Publication Date: 2013 Jun PMID: 23540831
Authors: Reineke, K. - Mathys, A. - Heinz, V. - Knorr, D.
Journal: Trends Microbiol

It is well known that spore germination and inactivation can be achieved within a broad temperature and pressure range. The existing literature, however, reports contradictory results concerning the effectiveness of different pressure-temperature combinations and the underlying inactivation mechanism(s). Much of the published kinetic data are prone to error as a result of unstable process conditions or an incomplete investigation of the entire inactivation pathway. Here, we review this field of research, and also discuss an inactivation mechanism of at least two steps and propose an inactivation model based on current data. Further, spore resistance properties and matrix interactions are linked to spore inactivation effectiveness.

post to: CiteULike

Reactivation of latent HIV by histone deacetylase inhibitors.

Publication Date: 2013 Jun PMID: 23517573
Authors: Shirakawa, K. - Chavez, L. - Hakre, S. - Calvanese, V. - Verdin, E.
Journal: Trends Microbiol

Latent HIV persists in CD4(+) T cells in infected patients under antiretroviral therapy (ART). Latency is associated with transcriptional silencing of the integrated provirus and driven, at least in part, by histone deacetylases (HDACs), a family of chromatin-associated proteins that regulate histone acetylation and the accessibility of DNA to transcription factors. Remarkably, inhibition of HDACs is sufficient to reactivate a fraction of latent HIV in a variety of experimental systems. This basic observation led to the shock and kill idea that forcing the transcriptional activation of HIV might lead to virus expression, to virus- or host-induced cell death of the reactivated cells, and to the eradication of the pool of latently infected cells. Such intervention might possibly lead to a cure for HIV-infected patients. Here, we review the basic biology of HDACs and their inhibitors, the role of HDACs in HIV latency, and recent efforts to use HDAC inhibitors to reactivate latent HIV in vitro and in vivo.

post to: CiteULike