Trends in microbiology

Diverse microbial interactions with the basement membrane barrier.

Publication Date: 2012 Jan 31 PMID: 22300759
Authors: Steukers, L. - Glorieux, S. - Vandekerckhove, A. P. - Favoreel, H. W. - Nauwynck, H. J.
Journal: Trends Microbiol

During primary contact with susceptible hosts, microorganisms face an array of barriers that thwart their invasion process. Passage through the basement membrane (BM), a 50-100-nm-thick crucial barrier underlying epithelia and endothelia, is a prerequisite for successful host invasion. Such passage allows pathogens to reach nerve endings or blood vessels in the stroma and to facilitate spread to internal organs. During evolution, several pathogens have developed different mechanisms to cross this dense matrix of sheet-like proteins. To breach the BM, some microorganisms have developed independent mechanisms, others hijack host cells that are able to transverse the BM (e.g. leukocytes and dendritic cells) and oncogenic microorganisms might even trigger metastatic processes in epithelial cells to penetrate the underlying BM.

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A metabolic network approach for the identification and prioritization of antimicrobial drug targets.

Publication Date: 2012 Jan 31 PMID: 22300758
Authors: Chavali, A. K. - D'Auria, K. M. - Hewlett, E. L. - Pearson, R. D. - Papin, J. A.
Journal: Trends Microbiol

For many infectious diseases, novel treatment options are needed in order to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies used to identify effective drug targets and highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents.

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Antibiotic resistance is ancient: implications for drug discovery.

Publication Date: 2012 Jan 25 PMID: 22284896
Authors: Wright, G. D. - Poinar, H.
Journal: Trends Microbiol

An unfailing observation over the past 70 years is that resistance to all antibiotics emerges eventually after use in the clinic. Where does this resistance come from? Recent work has shown that antibiotic resistance genes are common in metagenomes of ancient sediments. This prevalence of resistance, well before the use of antibiotics, denotes the importance of taking microbial chemical ecology and deep metagenomic profiling into account in the development and use of antibiotics.

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Engineering the robustness of industrial microbes through synthetic biology.

Publication Date: 2012 Jan 19 PMID: 22264657
Authors: Zhu, L. - Zhu, Y. - Zhang, Y. - Li, Y.
Journal: Trends Microbiol

Microbial fermentations and bioconversions play a central role in the production of pharmaceuticals, enzymes and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximized carbon flux towards target metabolites regardless of fluctuations in intracellular or extracellular environments. This requires cellular systems that maintain functional stability and dynamic homeostasis in a given physiological state, or manipulate transitions between different physiological states. Stable maintenance or smooth transition can be achieved through engineering of dynamic controllability, modular and hierarchical organization, or functional redundancy, three key features of biological robustness in a cellular system. This review summarizes how synthetic biology can be used to improve the robustness of industrial microbes.

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A cell-based backup to speed up pandemic influenza vaccine production.

Publication Date: 2012 Jan 16 PMID: 22257962
Authors: Lee, M. S. - Hu, A. Y.
Journal: Trends Microbiol

Influenza vaccines are currently produced through egg-based methods, with one drawback being that this system is slow to respond to the surging global demand during an influenza pandemic. Alternative influenza vaccine production strategies, such as using a cell-based strategy, should be considered in pandemic situations.

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Outbreaks of human monkeypox after cessation of smallpox vaccination.

Publication Date: 2012 Jan 10 PMID: 22239910
Authors: Reynolds, M. G. - Damon, I. K.
Journal: Trends Microbiol

The recent observation of a surge in human monkeypox in the Democratic Republic of the Congo (DRC) prompts the question of whether cessation of smallpox vaccination is driving the phenomenon, and if so, why is re-emergence not universal throughout the historic geographic range of the virus? Research addressing the virus's mechanisms for immune evasion and induction, as well as that directed at elucidating the genes involved in pathogenesis in different viral lineages (West African vs Congo Basin), provide insights to help explain why emergence appears to be geographically limited. Novel vaccines offer one solution to curtail the spread of this disease.

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