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      Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing

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          abstract

          Galleria mellonella (greater wax moth or honeycomb moth) has been introduced as an alternative model to study microbial infections. G. mellonella larvae can be easily and inexpensively obtained in large numbers and are simple to use as they don't require special lab equipment. There are no ethical constraints and their short life cycle makes them ideal for large-scale studies. Although insects lack an adaptive immune response, their innate immune response shows remarkable similarities with the immune response in vertebrates.

          This review gives a current update of what is known about the immune system of G. mellonella and provides an extensive overview of how G. mellonella is used to study the virulence of Gram-positive and Gram-negative bacteria. In addition, the use of G. mellonella to evaluate the efficacy of antimicrobial agents and experimental phage therapy are also discussed. The review concludes with a critical assessment of the current limitatons of G. mellonella infection models.

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          Most cited references133

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          Role of the prophenoloxidase-activating system in invertebrate immunity.

          The melanization reaction, which is a common response to parasite entry in invertebrate animals, especially arthropods, is due to the activity of an oxidoreductase, phenoloxidase. This enzyme is part of a complex system of proteinases, pattern recognition proteins and proteinase inhibitors constituting the so-called prophenoloxidase-activating system. It is proposed to be a non-self recognition system because conversion of prophenoloxidase to active enzyme can be brought about by minuscule amounts of molecules such as lipopolysaccharide, peptidoglycan and beta-1, 3-glucans from micro-organisms. Several components of this system recently have been isolated and their structure determined.
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            Positive correlation between virulence of Pseudomonas aeruginosa mutants in mice and insects.

            Strain PA14, a human clinical isolate of Pseudomonas aeruginosa, is pathogenic in mice and insects (Galleria mellonella). Analysis of 32 different PA14 mutants in these two hosts showed a novel positive correlation in the virulence patterns. Thus, G. mellonella is a good model system for identifying mammalian virulence factors of P. aeruginosa.
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              Phage-Antibiotic Synergy (PAS): β-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth

              Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage ΦMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with β-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.
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                Author and article information

                Journal
                Virulence
                Virulence
                KVIR
                Virulence
                Taylor & Francis
                2150-5594
                2150-5608
                April 2016
                5 January 2016
                5 January 2016
                : 7
                : 3 , Bloodstream Infections
                : 214-229
                Affiliations
                [a ]Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland , Auckland, New Zealand
                [b ]Maurice Wilkins Center, University of Auckland , Auckland, New Zealand
                Author notes
                CONTACT Jacelyn Mei San Loh mj.loh@ 123456auckland.ac.nz ; Thomas Proft t.proft@ 123456auckland.ac.nz School of Medical Sciences, University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.

                Color versions of one or more of the figures in this article can be found online at www.tandfonline.com/kvir.

                Supplemental data for this article can be accessed on the publisher's website.

                Article
                1135289
                10.1080/21505594.2015.1135289
                4871635
                26730990
                30aa7b72-e114-413a-85fc-f8ef21f0bdb6
                © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License http://creativecommons.org/licenses/by-nc/3.0/, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 18 November 2015
                : 15 December 2015
                : 16 December 2015
                Page count
                Figures: 1, Tables: 2, References: 151, Pages: 16
                Categories
                Review

                Infectious disease & Microbiology
                antimicrobial drug testing,galleria mellonella,gram-positive pathogens,gram-negative pathogens,infection model,innate immunity,wax worm

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