scholarly journals Prospecting the insect model, Galleria mellonella, for gut-related pathobiology

2020 ◽  
Author(s):  
◽  
Helena Emery
Keyword(s):  
Gastrointestinal Tract ◽  
Galleria Mellonella ◽  
Communicable Disease ◽  
Oral Route ◽  
Cordyceps Sinensis ◽  
Shellfish Poisoning ◽  
In Vivo Models ◽  
Toxicological Assessment

Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human genes and is the most widespread vertebrate model in use. Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host’s capacity to recover from subacute chemical and microbial disruptors.

scholarly journals Hepatitis E Virus Immunopathogenesis

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1180
Author(s):  
Kush Kumar Yadav ◽  
Scott P. Kenney
Keyword(s):  
Hepatitis E Virus ◽  
Organ Transplant ◽  
Hepatitis E ◽  
Oral Route ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
In Vivo Models ◽  
Transplant Patients

Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.

scholarly journals Virulence of the emerging pathogen, Burkholderia pseudomallei, depends upon the O-linked oligosaccharyltransferase, PglL

2020 ◽  
Vol 15 (4) ◽  
pp. 241-257
Author(s):  
Samuel J Willcocks ◽  
Carmen Denman ◽  
Felipe Cia ◽  
Elizabeth McCarthy ◽  
Jon Cuccui ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Galleria Mellonella ◽  
In Vitro Assays ◽  
In Vivo Models ◽  
Bacterial Fitness ◽  
Isogenic Mutants ◽  
Type Strains ◽  
Broad Role

Aim: We sought to characterize the contribution of the O-OTase, PglL, to virulence in two Burkholderia spp. by comparing isogenic mutants in Burkholderia pseudomallei with the related species, Burkholderia thailandensis. Materials & methods: We utilized an array of in vitro assays in addition to Galleria mellonella and murine in vivo models to assess virulence of the mutant and wild-type strains in each Burkholderia species. Results: We found that pglL contributes to biofilm and twitching motility in both species. PglL uniquely affected morphology; cell invasion; intracellular motility; plaque formation and intergenus competition in B. pseudomallei. This mutant was attenuated in the murine model, and extended survival in a vaccine-challenge experiment. Conclusion: Our data support a broad role for pglL in bacterial fitness and virulence, particularly in B. pseudomallei.

scholarly journals In Vitro or in Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much do We Know?

2020 ◽  
Author(s):  
Maritza Torres ◽  
Hans De Cock ◽  
Adriana Marcela Celis Ramírez
Keyword(s):  
Galleria Mellonella ◽  
Fungal Infections ◽  
Ex Vivo ◽  
Model Organisms ◽  
In Vivo Models ◽  
Fungal Host ◽  
Alternative Models ◽  
Malassezia Spp

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

scholarly journals In Vitro or In Vivo Models, the Next Frontier for Unraveling Interactions between Malassezia spp. and Hosts. How Much Do We Know?

2020 ◽  
Vol 6 (3) ◽  
pp. 155
Author(s):  
Maritza Torres ◽  
Hans de Cock ◽  
Adriana Marcela Celis Ramírez
Keyword(s):  
Galleria Mellonella ◽  
Fungal Infections ◽  
Model Organisms ◽  
In Vivo Models ◽  
Alternative Models ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
Malassezia Spp

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host–microbe interactions of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host–microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

DksA is a central regulatory switch for stress protection and virulence in Acinetobacter baumannii

2021 ◽  
Author(s):  
Ram Maharjan ◽  
Geraldine Sulivan ◽  
Felise Adams ◽  
Natasha Delgado ◽  
Lucie Semenec ◽  
...  
Keyword(s):  
Stress Response ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Term Survival ◽  
In Vivo Models ◽  
Molecular Control ◽  
Stress Protection

Abstract Bacterial coordination of stress resistance mechanisms in harsh environments is key to long-term survival and evolutionary success. In many Gram-negative pathogens, both general- and specific-stress response are controlled by alternative sigma factors such as RpoS. The critically important pathogen Acinetobacter baumannii is notoriously recalcitrant to external stressors, yet it lacks RpoS, so the molecular control of its resilience remains unclear. Here, we used transposon insertion sequencing to characterize the molecular responses of Acinetobacter baumannii to two biologically-important metals stressors, zinc and copper, and discovered that the transcriptional regulator DksA acts as a major regulatory stress-protection switch. We mapped the highly pleiotropic nature of DksA using transcriptomics and phenomics and found that it controls ribosomal protein expression, metabolism of gluconeogenic substrates and survival in stresses that cause oxidative damage. A. baumannii strains lacking DksA were no longer virulent in both murine and Galleria mellonella in vivo models. In vitro, DksA mutants exhibited increased sensitivity to human serum and antibiotics yet promoted biofilm and capsule formation. Our study provides detailed insight into the unique role that DksA plays in stress protection and virulence for A. baumannii and lays the groundwork for understanding of RpoS-independent regulatory general stress response.

scholarly journals 787. The Addition of Avibactam Augments the Activity of Piperacillin Against Mycobacterium abscessus in vitro, and Is Effective in Treating M. abscessus Infection in a Galleria mellonella in vivo Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S281-S282
Author(s):  
Michal Meir ◽  
Daniel Barkan
Keyword(s):  
Galleria Mellonella ◽  
Inhibitory Effect ◽  
Mycobacterium Abscessus ◽  
In Vivo Model ◽  
Great Promise ◽  
Infection Model ◽  
In Vivo Models ◽  
Antimicrobial Treatments

Abstract Background Mycobacterium abscessus is an emerging multi-drug-resistant pathogen, harboring the β-lactamse BlaMAB. Avibactam is a non-β-lactam, β-lactamase inhibitor shown to inhibit BlaMAB and improve the efficacy of ampicillin for M. abscessus infections in in vitro and in vivo models. Whether the addition of avibactam to piperacillin enables use of the latter against M. abscessus is unknown Methods We used a recombinant, luminescent M. abscessus to measure the reduction of MIC to meropenem, ampicillin, and piperacillin induced by avibactam. We then used our previously established G. mellonella infection model (Figure 1)1 to evaluate the effect of antimicrobial treatments in vivo. Results Addition of avibactam (4 µg/mL) consistently decreased MIC of ampicillin and piperacillin by 16 and 16–32-fold, respectively, but as expected had no significant effect on meropenem MIC (Figure 2). We inoculated 60 G. mellonella larvae with luminescent M. abscessus on day 0, and treated larvae with meropenem, piperacillin, avibactam alone, or piperacillin combined with avibactam on days 2 and 3. Using IVIS® imaging, we measured infection progression in live infected larvae on day 4. Larvae treated with meropenem and piperacillin–avibactam had significantly lower infection burden compared with untreated controls (P < 0.0001 and P = 0.004, respectively). Piperacillin and avibactam alone had no significant inhibitory effect (Figure 3). Conclusion Our findings suggest that the piperacillin–avibactam combination is effective against M. abscessus infections. This novel combination may hold a great promise for patients with cystic fibrosis suffering from M. abscessus, Pseudomonas aeruginosa, and/or Staphylococcus aureus co-infections. The G. mellonella infection model may be used in future studies to assess the efficacy of various antimicrobials and antimicrobial combinations on M. abscessus, P. aeruginosa, and S. aureus co-infections. Reference 1. Meir M et al. Antimicrob Agents Chemother. 2018. Disclosures All authors: No reported disclosures.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

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