Galleria mellonella as a Model System for Studying Listeria Pathogenesis

Abstract

Essential aspects of the innate immune response to microbial infection are conserved between insects and mammals. This has generated interest in using insects as model organisms to study host-microbe interactions. We used the greater wax moth Galleria mellonella, which can be reared at 37°C, as a model host for examining the virulence potential of Listeria spp. Here we report that Galleria is an excellent surrogate model of listerial septic infection, capable of clearly distinguishing between pathogenic and nonpathogenic Listeria strains and even between virulent and attenuated Listeria monocytogenes strains. Virulence required listerial genes hitherto implicated in the mouse infection model and was linked to strong antimicrobial activities in both hemolymph and hemocytes of infected larvae. Following Listeria infection, the expression of immune defense genes such as those for lysozyme, galiomycin, gallerimycin, and insect metalloproteinase inhibitor (IMPI) was sequentially induced. Preinduction of antimicrobial activity by treatment of larvae with lipopolysaccharide (LPS) significantly improved survival against subsequent L. monocytogenes challenge and strong antilisterial activity was detected in the hemolymph of LPS pretreated larvae. We conclude that the severity of septic infection with L. monocytogenes is modulated primarily by innate immune responses, and we suggest the use of Galleria as a relatively simple, nonmammalian model system that can be used to assess the virulence of strains of Listeria spp. isolated from a wide variety of settings from both the clinic and the environment.Listeriae are rod-shaped, motile, facultative, anaerobic Gram-positive bacteria that are ubiquitously distributed in the environment (28). Of the six species that comprise the genus Listeria, only L. monocytogenes and L. ivanovii are pathogenic and cause disease, while strains of the species L. innocua, L. welshimeri, L. seeligeri, and L. grayi are generally considered to be nonpathogenic (26). L. monocytogenes is a major foodborne pathogen, and listeriosis is an invasive disease that in its severest form can lead to meningitis, meningoencephalitis, septicemia, and abortions (38). Listeriosis occurs primarily in pregnant women, newborn infants, and the elderly as well as in immunocompromised patients, with a mortality rate of about 30% (22,36). The virulence of L. monocytogenes has been linked to a 9.6-kb pathogenicity island designated vgc (virulence gene cluster) that comprises six genes encoding its major virulence determinants. These are (i) prfA, a master regulator of many known listerial virulence genes; (ii) hly, encoding listeriolysin, a hemolysin required for bacterial escape from the host primary vacuole to the host cytoplasm; (iii) two phospholipase genes denoted plcA and plcB, for facilitating lysis of host cell membranes; (iv) actA, encoding a surface bound protein that directs polymerization of host cell actin and is required for intracellular motility; and (v) mpl, encoding a metalloproteinase which is thought t...

Legionella pneumophila Pathogenesis in the Galleria mellonella Infection Model

“…A T4SS-deficient mutant did not show any virulence even at the highest (10 7 CFU) inoculum injected. This contrasts observations described for the G. mellonella model of Listeria infection, in which nonpathogenic strains with increasing doses up to 10 7 CFU per larva also induced mortality (23,34). It was proposed that this could be attributed to a form of sepsis, and subsequent death was caused by bacterial overload and was not due to specific virulence factors.…”

“…following wild-type L. pneumophila infection. Depletion of circulating hemocytes upon bacterial infection has previously been reported and correlated with G. mellonella mortality caused by pathogenic fungi and Gram-negative bacteria (9,34). This loss may be due to the death of infected hemocytes or the sequestration of hemocytes in nodules or to a combination of both.…”

Niklozamidin Galleria mellonella L. (Lepidoptera: Pyralidae)'nın bazı biyolojik ve fizyolojik özelliklerine etkisi

“…Bu çalışmada kullanılan büyük bal mumu güvesi G. mellonella insan ve hayvanlarda enfeksiyon oluşturan bazı küf, mantar ve bakterilerin patojenitesini belirlemede memeli deney hayvanlarına alternatif omurgasız bir konukçu model sistemi olarak (Miyata et al, 2003;Altincicek et al, 2007;Joyce et al, 2010;Mukherjee et al, 2010) ve böcek-insektisit etkileşimi ile ilgili biyokimyasal ve fizyolojik çalışmalar için model olarak kullanılabilen oldukça uygun bir böcektir (Büyükgüzel & İçen, 2004;Büyükgüzel & Kalender, 2008). Mevcut çalışmada antihelmintik ilaçların zararlı böceklerin mücadelesinde insektisit olarak kullanılabilirliğinin belirlenmesi amacıyla, niklozamidin G. mellonella gelişme dönemleri ve ergin biyolojisi üzerindeki etkileri araştırılmıştır.…”

Insects emerge as valuable model hosts to explore virulence

“…21 In addition, it has been established as a surrogate model host for Listeria monocytogenes, the infective agent causing listeriosis, a major foodborne disease that occurs primarily in pregnant women, newborn infants and the elderly as well as in immune compromised patients, with a mortality rate of about 30%. 22 The potential of insect model hosts such as D. melanogaster and G. mellonella in applied medical research can be expanded beyond their established roles as whole-animal-high-throughput-systems for in vivo testing of human pathogens or antibiotics 10,13 to include their value as a source of novel anti-infective drugs. 23,24 Insects and humans share some evolutionary conserved families of antimicrobial peptides such as the defensins.…”