The Experts below are selected from a list of 627 Experts worldwide ranked by ideXlab platform
Brandon C Ogbunugafor - One of the best experts on this subject based on the ideXlab platform.
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proteostasis environment shapes higher order epistasis operating on antibiotic resistance
Genetics, 2019Co-Authors: Rafael F Guerrero, Samuel V Scarpino, Joao V Rodrigues, Daniel L Hartl, Brandon C OgbunugaforAbstract:Recent studies have affirmed that higher-order epistasis is ubiquitous and can have large effects on complex traits. Yet, we lack frameworks for understanding how epistatic interactions are influenced by central features of cell physiology. In this study, we assess how protein quality control machinery-a critical component of cell physiology-affects epistasis for different traits related to bacterial resistance to antibiotics. Specifically, we disentangle the interactions between different protein quality control genetic backgrounds and two sets of mutations: (i) SNPs associated with resistance to antibiotics in an essential bacterial enzyme (dihydrofolate reductase, or DHFR) and (ii) differing DHFR bacterial species-specific amino acid background sequences ( Escherichia coli , Listeria grayi , Chlamydia muridarum ). In doing so, we improve on generic observations that epistasis is widespread by discussing how patterns of epistasis can be partly explained by specific interactions between mutations in an essential enzyme and genes associated with proteostasis. These findings speak to the role of environmental and genotypic context in modulating higher-order epistasis, with direct implications for evolutionary theory, genetic modification technology, and efforts to manage antimicrobial resistance.
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proteostasis environment shapes higher order epistasis operating on antibiotic resistance
bioRxiv, 2018Co-Authors: Rafael F Guerrero, Samuel V Scarpino, Joao V Rodrigues, Daniel L Hartl, Brandon C OgbunugaforAbstract:ABSTRACT Recent studies have shown that higher-order epistasis is ubiquitous and can have large effects on complex traits. Yet, we lack frameworks for understanding how epistatic interactions are influenced by basic aspects of cell physiology. In this study, we assess how protein quality control machinery—a critical component of cell physiology—affects epistasis for different traits related to bacterial resistance to antibiotics. Specifically, we attempt to disentangle the interactions between different protein quality control genetic backgrounds and two sets of mutations: (i) SNPs associated with resistance to antibiotics in an essential bacterial enzyme (dihydrofolate reductase, or DHFR) and (ii) differing DHFR bacterial species-specific amino acid background sequences (Escherichia coli, Listeria grayi, and Chlamydia muridarum). In doing so, we add nuance to the generic observation that non-linear genetic interactions are widespread and capricious in nature, by proposing a mechanistically-grounded analysis of how proteostasis shapes epistasis. These findings simultaneously fortify and demystify the role of environmental context in modulating higher-order epistasis, with direct implications for evolutionary theory, genetic modification technology, and efforts to manage antimicrobial resistance.
Tonk Miray - One of the best experts on this subject based on the ideXlab platform.
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
'MDPI AG', 2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.EC/H2020/713683/EU/H.C. Ørsted Fellows Programme – co-funded by Marie Skłodowska Curie Actions (COFUNDfellowsDTU)/COFUNDfellowsDT
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 – 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1–4 (HoloTickCores 1–4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.JJV is supported by Project FIT (Pharmacology, Immunotherapy, nanoToxicology), which was funded by the European Regional Development Fund and acknowledges a grant from the research organization RVO: RO0516. Transcriptome analysis of I. holocyclus viscera and salivary glands was funded by the Australian Research Council linkage project LP120200836 and Elanco Animal Health. MT and AV would like to acknowledge generous funding by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG) and the LOEWE Center for Insect Biotechnology and Bioresources.Peer reviewe
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:International audienceTick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
Cabezas-cruz Alejandro - One of the best experts on this subject based on the ideXlab platform.
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
'MDPI AG', 2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.EC/H2020/713683/EU/H.C. Ørsted Fellows Programme – co-funded by Marie Skłodowska Curie Actions (COFUNDfellowsDTU)/COFUNDfellowsDT
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 – 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1–4 (HoloTickCores 1–4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.JJV is supported by Project FIT (Pharmacology, Immunotherapy, nanoToxicology), which was funded by the European Regional Development Fund and acknowledges a grant from the research organization RVO: RO0516. Transcriptome analysis of I. holocyclus viscera and salivary glands was funded by the Australian Research Council linkage project LP120200836 and Elanco Animal Health. MT and AV would like to acknowledge generous funding by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG) and the LOEWE Center for Insect Biotechnology and Bioresources.Peer reviewe
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:International audienceTick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
Vilcinskas Andreas - One of the best experts on this subject based on the ideXlab platform.
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
'MDPI AG', 2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications
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Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus
2021Co-Authors: Rügen Nicolai, Cabezas-cruz Alejandro, Vilcinskas Andreas, Jenkins, Timothy P., Wielsch Natalie, Vogel Heiko, Hempel Benjamin-florian, Süssmuth, Roderich D., Ainsworth Stuart, Tonk MirayAbstract:Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.EC/H2020/713683/EU/H.C. Ørsted Fellows Programme – co-funded by Marie Skłodowska Curie Actions (COFUNDfellowsDTU)/COFUNDfellowsDT
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:Tick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 – 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1–4 (HoloTickCores 1–4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity.JJV is supported by Project FIT (Pharmacology, Immunotherapy, nanoToxicology), which was funded by the European Regional Development Fund and acknowledges a grant from the research organization RVO: RO0516. Transcriptome analysis of I. holocyclus viscera and salivary glands was funded by the Australian Research Council linkage project LP120200836 and Elanco Animal Health. MT and AV would like to acknowledge generous funding by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK) via the LOEWE Centre for Translational Biodiversity Genomics (LOEWE-TBG) and the LOEWE Center for Insect Biotechnology and Bioresources.Peer reviewe
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Antibacterial and antifungal activity of defensins from the Australian paralysis tick, Ixodes holocyclus
'Elsevier BV', 2019Co-Authors: Cabezas-cruz Alejandro, Barrero, Roberto A., Tonk Miray, Bleackley, Mark R., Valdes, James J., Hernández-jarguín Angélica, Moutailler Sara, Vilcinskas Andreas, Richard-forget Florence, Anderson, Marilyn A.Abstract:International audienceTick innate immunity involves humoral and cellular responses. Among the humoral effector molecules in ticks are the defensins which are a family of small peptides with a conserved γ-core motif that is crucial for their antimicrobial activity. Defensin families have been identified in several hard and soft tick species. However, little is known about the presence and antimicrobial activity of defensins from the Australian paralysis tick Ixodes holocyclus. In this study the I. holocyclus transcriptome was searched for the presence of defensins. Unique and non-redundant defensin sequences were identified and designated as holosins 1 - 5. The antimicrobial activity of holosins 2 and 3 and of the predicted γ-cores of holosins 1-4 (HoloTickCores 1-4), was assessed using Gram-negative and Gram-positive bacteria as well as the fungus Fusarium graminearum and the yeast Candida albicans. All holosins had molecular features that are conserved in other tick defensins. Furthermore holosins 2 and 3 were very active against the Gram-positive bacteria Staphylococcus aureus and Listeria grayi. Holosins 2 and 3 were also active against F. graminearum and C. albicans and 5 μM of peptide abrogate the growth of these microorganisms. The activity of the synthetic γ-cores was lower than that of the mature defensins apart from HoloTickCore 2 which had activity comparable to mature holosin 2 against the Gram-negative bacterium Escherichia coli. This study reveals the presence of a multigene defensin family in I. holocyclus with wide antimicrobial activity
Rafael F Guerrero - One of the best experts on this subject based on the ideXlab platform.
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proteostasis environment shapes higher order epistasis operating on antibiotic resistance
Genetics, 2019Co-Authors: Rafael F Guerrero, Samuel V Scarpino, Joao V Rodrigues, Daniel L Hartl, Brandon C OgbunugaforAbstract:Recent studies have affirmed that higher-order epistasis is ubiquitous and can have large effects on complex traits. Yet, we lack frameworks for understanding how epistatic interactions are influenced by central features of cell physiology. In this study, we assess how protein quality control machinery-a critical component of cell physiology-affects epistasis for different traits related to bacterial resistance to antibiotics. Specifically, we disentangle the interactions between different protein quality control genetic backgrounds and two sets of mutations: (i) SNPs associated with resistance to antibiotics in an essential bacterial enzyme (dihydrofolate reductase, or DHFR) and (ii) differing DHFR bacterial species-specific amino acid background sequences ( Escherichia coli , Listeria grayi , Chlamydia muridarum ). In doing so, we improve on generic observations that epistasis is widespread by discussing how patterns of epistasis can be partly explained by specific interactions between mutations in an essential enzyme and genes associated with proteostasis. These findings speak to the role of environmental and genotypic context in modulating higher-order epistasis, with direct implications for evolutionary theory, genetic modification technology, and efforts to manage antimicrobial resistance.
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proteostasis environment shapes higher order epistasis operating on antibiotic resistance
bioRxiv, 2018Co-Authors: Rafael F Guerrero, Samuel V Scarpino, Joao V Rodrigues, Daniel L Hartl, Brandon C OgbunugaforAbstract:ABSTRACT Recent studies have shown that higher-order epistasis is ubiquitous and can have large effects on complex traits. Yet, we lack frameworks for understanding how epistatic interactions are influenced by basic aspects of cell physiology. In this study, we assess how protein quality control machinery—a critical component of cell physiology—affects epistasis for different traits related to bacterial resistance to antibiotics. Specifically, we attempt to disentangle the interactions between different protein quality control genetic backgrounds and two sets of mutations: (i) SNPs associated with resistance to antibiotics in an essential bacterial enzyme (dihydrofolate reductase, or DHFR) and (ii) differing DHFR bacterial species-specific amino acid background sequences (Escherichia coli, Listeria grayi, and Chlamydia muridarum). In doing so, we add nuance to the generic observation that non-linear genetic interactions are widespread and capricious in nature, by proposing a mechanistically-grounded analysis of how proteostasis shapes epistasis. These findings simultaneously fortify and demystify the role of environmental context in modulating higher-order epistasis, with direct implications for evolutionary theory, genetic modification technology, and efforts to manage antimicrobial resistance.