The genome of the ant Tetramorium bicarinatum reveals a tandem organization of venom peptides genes allowing the prediction of their regulatory and evolutionary profiles.

BACKGROUND: Venoms have evolved independently over a hundred times in the animal kingdom to deter predators and/or subdue prey. Venoms are cocktails of various secreted toxins, whose origin and diversification provide an appealing system for evolutionary researchers. Previous studies of the ant venom of Tetramorium bicarinatum revealed several Myrmicitoxin (MYRTX) peptides that gathered into seven precursor families suggesting different evolutionary origins. Analysis of the T. bicarinatum genome enabling further genomic approaches was necessary to understand the processes underlying the evolution of these myrmicitoxins. RESULTS: Here, we sequenced the genome of Tetramorium bicarinatum and reported the organisation of 44 venom peptide genes (vpg). Of the eleven chromosomes that make up the genome of T. bicarinatum, four carry the vpg which are organized in tandem repeats. This organisation together with the ML evolutionary analysis of vpg sequences, is consistent with evolution by local duplication of ancestral genes for each precursor family. The structure of the vpg into two or three exons is conserved after duplication events while the promoter regions are the least conserved parts of the vpg even for genes with highly identical sequences. This suggests that enhancer sequences were not involved in duplication events, but were recruited from surrounding regions. Expression level analysis revealed that most vpg are highly expressed in venom glands, although one gene or group of genes is much more highly expressed in each family. Finally, the examination of the genomic data revealed that several genes encoding transcription factors (TFs) are highly expressed in the venom glands. The search for binding sites (BS) of these TFs in the vpg promoters revealed hot spots of GATA sites in several vpg families. CONCLUSION: In this pioneering investigation on ant venom genes, we provide a high-quality assembly genome and the annotation of venom peptide genes that we think can fosters further genomic research to understand the evolutionary history of ant venom biochemistry.

Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells.

Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant "Myrmecia pilosula", as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3's cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (p < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results.

Ant Venom-Based Ceramide Therapy Is Effective Against Atopic Dermatitis In Vivo.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with relatively few therapeutic alternatives. These include corticosteroids, which address inflammation but not superinfection, and Januse kinase (JAK) inhibitors, which have a US Food and Drug Administration (FDA) black box for potential carcinogenicity. METHODS: We demonstrate that S14, a synthetic derivative of ant venom-derived solenopsin, has potent anti inflammatory effects on the OVA murine model of atopic dermatitis. S14 has demonstrated prior activity in murine psoriasis and has the benefit of ceramide anti-inflammatory effects without being able to be metabolized into proinflammatory sphingosine-1 phosphate. RESULTS: The efficacy of S14 accompanied by the induction of IL-12 suggests a commonality in inflammatory skin disorders, and our results suggest that pharmacological ceramide restoration will be broadly effective for inflammatory skin disease. CONCLUSIONS: Solenopsin derivative S14 has anti-inflammatory effects in murine models of AD and psoriasis. This makes S14 a strong candidate for human use, and pre-IND studies are warranted.J Drugs Dermatol. 2023;22(10):1001-1006 doi:10.36849/JDD.7308.

Discovery of an Insect Neuroactive Helix Ring Peptide from Ant Venom.

Ants are among the most abundant terrestrial invertebrate predators on Earth. To overwhelm their prey, they employ several remarkable behavioral, physiological, and biochemical innovations, including an effective paralytic venom. Ant venoms are thus cocktails of toxins finely tuned to disrupt the physiological systems of insect prey. They have received little attention yet hold great promise for the discovery of novel insecticidal molecules. To identify insect-neurotoxins from ant venoms, we screened the paralytic activity on blowflies of nine synthetic peptides previously characterized in the venom of Tetramorium bicarinatum. We selected peptide U11, a 34-amino acid peptide, for further insecticidal, structural, and pharmacological experiments. Insecticidal assays revealed that U11 is one of the most paralytic peptides ever reported from ant venoms against blowflies and is also capable of paralyzing honeybees. An NMR spectroscopy of U11 uncovered a unique scaffold, featuring a compact triangular ring helix structure stabilized by a single disulfide bond. Pharmacological assays using Drosophila S2 cells demonstrated that U11 is not cytotoxic, but suggest that it may modulate potassium conductance, which structural data seem to corroborate and will be confirmed in a future extended pharmacological investigation. The results described in this paper demonstrate that ant venom is a promising reservoir for the discovery of neuroactive insecticidal peptides.

Antimicrobial Peptide Arsenal Predicted from the Venom Gland Transcriptome of the Tropical Trap-Jaw Ant Odontomachus chelifer.

With about 13,000 known species, ants are the most abundant venomous insects. Their venom consists of polypeptides, enzymes, alkaloids, biogenic amines, formic acid, and hydrocarbons. In this study, we investigated, using in silico techniques, the peptides composing a putative antimicrobial arsenal from the venom gland of the neotropical trap-jaw ant Odontomachus chelifer. Focusing on transcripts from the body and venom gland of this insect, it was possible to determine the gland secretome, which contained about 1022 peptides with putative signal peptides. The majority of these peptides (75.5%) were unknown, not matching any reference database, motivating us to extract functional insights via machine learning-based techniques. With several complementary methodologies, we investigated the existence of antimicrobial peptides (AMPs) in the venom gland of O. chelifer, finding 112 non-redundant candidates. Candidate AMPs were predicted to be more globular and hemolytic than the remaining peptides in the secretome. There is evidence of transcription for 97% of AMP candidates across the same ant genus, with one of them also verified as translated, thus supporting our findings. Most of these potential antimicrobial sequences (94.8%) matched transcripts from the ant's body, indicating their role not solely as venom toxins.

Proteinaceous Venom Expression of the Yellow Meadow Ant, Lasius flavus (Hymenoptera: Formicidae).

Ants are one of the important groups of venomous animals with about 14,000 described species. Studies so far focused on the discovery of venom proteins are only available for limited stinging ants, and the proteinaceous compositions of the stingless ants are completely unknown. Here, we used the transcriptomic approach to identify venom components from the yellow meadow ant, Lasius flavus, a stingless ant. The transcriptomic analysis yielded an extraordinary simplicity of the venom expression profile, with 17 venom proteins, such as phospholipase B, odorant binding protein, and apolipoprotein D. Ten of them were discovered as novel toxins for future functional investigations. Quantitative real time PCR analysis revealed that genes encoding the identified venom proteins display exclusively or highly expression profiles in venom glands, validating them as venom compositions. Our findings contribute to the understanding of the evolutional diversity of toxins between stinging and stingless ants.

Transcriptomic and biochemical analysis from the venom gland of the neotropical ant Odontomachus chelifer.

The genus Odontomachus is widely distributed in neotropical areas throughout Central and South America. It is a stinging ant that subdues its prey (insects) by injecting them a cocktail of toxic molecules (venom). Ant venoms are generally composed of formic acid, alkaloids, hydrocarbons, amines, peptides, and proteins. Odontomachus chelifer is an ant that inhabits neotropical regions from Mexico to Argentina. Unlike the venom of other animals such as scorpions, spiders and snakes, this ant venom has seldom been analyzed comprehensively, and their compositions are not yet completely known. In the present study, we performed a partial investigation of enzymatic and functional activities of O. chelifer ant venom, and we provide a global insight on the transcripts expressed in the venom gland to better understand their properties. The crude venom showed phospholipase A2 and antiparasitic activities. RNA sequencing (Illumina platform) of the venom gland of O. chelifer generated 61, 422, 898 reads and de novo assembly Trinity generated 50,220 contigs. BUSCO analysis against Arthropoda_db10 showed that 92.89% of the BUSCO groups have complete gene representation (single-copy or duplicated), while 4.05% are only partially recovered, and 3.06% are missing. The 30 most expressed genes in O. chelifer venom gland transcriptome included important transcripts involved in venom function such as U-poneritoxin (01)-Om1a-like (pilosulin), chitinase 2, venom allergen 3, chymotrypsin 1 and 2 and glutathione S-transferase. Analysis of the molecular function revealed that the largest number of transcripts were related to catalytic activity, including phospholipases. These data emphasize the potential of O. chelifer venom for prospection of molecules with biotechnological application.

Bioactivity Profiling of In Silico Predicted Linear Toxins from the Ants Myrmica rubra and Myrmica ruginodis.

The venoms of ants (Formicidae) are a promising source of novel bioactive molecules with potential for clinical and agricultural applications. However, despite the rich diversity of ant species, only a fraction of this vast resource has been thoroughly examined in bioprospecting programs. Previous studies focusing on the venom of Central European ants (subfamily Myrmicinae) identified a number of short linear decapeptides and nonapeptides resembling antimicrobial peptides (AMPs). Here, we describe the in silico approach and bioactivity profiling of 10 novel AMP-like peptides from the fellow Central European myrmicine ants Myrmica rubra and Myrmica ruginodis. Using the sequences of known ant venom peptides as queries, we screened the venom gland transcriptomes of both species. We found transcripts of nine novel decapeptides and one novel nonapeptide. The corresponding peptides were synthesized for bioactivity profiling in a broad panel of assays consisting of tests for cytotoxicity as well as antiviral, insecticidal, and antimicrobial activity. U-MYRTX-Mrug5a showed moderately potent antimicrobial effects against several bacteria, including clinically relevant pathogens such as Listeria monocytogenes and Staphylococcus epidermidis, but high concentrations showed negligible cytotoxicity. U-MYRTX-Mrug5a is, therefore, a probable lead for the development of novel peptide-based antibiotics.

Venomics survey of six myrmicine ants provides insights into the molecular and structural diversity of their peptide toxins.

Among ants, Myrmicinae represents the most speciose subfamily. The venom composition previously described for these social insects is extremely variable, with alkaloids predominant in some genera while, conversely, proteomics studies have revealed that some myrmicine ant venoms are peptide-rich. Using integrated transcriptomic and proteomic approaches, we characterized the venom peptidomes of six ants belonging to the different tribes of Myrmicinae. We identified a total of 79 myrmicitoxins precursors which can be classified into 38 peptide families according to their mature sequences. Myrmicine ant venom peptidomes showed heterogeneous compositions, with linear and disulfide-bonded monomers as well as dimeric toxins. Several peptide families were exclusive to a single venom whereas some were retrieved in multiple species. A hierarchical clustering analysis of precursor signal sequences led us to divide the myrmicitoxins precursors into eight families, including some that have already been described in other aculeate hymenoptera such as secapin-like peptides and voltage-gated sodium channel (NaV) toxins. Evolutionary and structural analyses of two representatives of these families highlighted variation and conserved patterns that might be crucial to explain myrmicine venom peptide functional adaptations to biological targets.

Studying the Rationale of Fire Ant Sting Therapy Usage by the Tribal Natives of Bastar Revealed Ant Venom-Derived Peptides with Promising Anti-Malarial Activity.

Prevailing drug resistance in malaria imposes the major roadblock for the existing interventions necessitating the timely need to search for alternative therapies. Ants in Solenopsis spp, termed 'Fire ants', are well known for their aggressive behavior, which leads to the release of toxic venom. Notably, the tribal natives of the malaria-laden densely forested Bastar region, Chhattisgarh, India, use fire ant sting-based therapy to cure malaria-like high fever. Inspired by this, we have collected the fire ants from the forest of Bastar and extracted peptide and alkaloid fractions from ant venom using HPLC and analyzed them by LC/MS-based applications. Evaluation of the anti-malarial efficacy of these peptide fractions demonstrated a significant reduction in the growth of Plasmodium falciparum (Pf 3D7) in vitro, whereas the alkaloid fraction showed a negligible effect. in vitro hemolytic activity confirmed the venom peptide fraction to be non-hemolytic. Additionally, the venom peptide fraction is purely non-toxic to HepG2 cells. Anti-malarial efficiency of the same in Plasmodium berghei ANKA infected mice models showed a drastic reduction in parasitemia representing promising anti-malarial activity. Overall, our study has unraveled the scientific rationale underlying fire ant sting therapy used as a tribal naturotherapy for curing malaria-like fever, thus, introducing a way forward to develop nature-inspired anti-malarial chemotherapeutics.

Antimicrobial potential of a ponericin-like peptide isolated from Bombyx mori L. hemolymph in response to Pseudomonas aeruginosa infection.

The main effectors in the innate immune system of Bombyx mori L. are antimicrobial peptides (AMPs). Here, we infected B. mori with varied inoculum sizes of Pseudomonas aeruginosa ATCC 25668 cells to investigate changes in morpho-anatomical responses, physiological processes and AMP production. Ultraviolet-visible spectra revealed a sharp change in λmax from 278 to 285 nm (bathochromic shift) in the hemolymph of infected B. mori incubated for 24 h. Further, Fourier Transform InfraRed studies on the hemolymph extracted from the infected B. mori showed a peak at 1550 cm-1, indicating the presence of α-helical peptides. The peptide fraction was obtained through methanol, acetic acid and water mixture (90:1:9) extraction, followed by peptide purification using Reverse Phase High Performance Liquid Chromatography. The fraction exhibiting antibacterial properties was collected and characterized by Matrix-Assisted Laser Desorption/Ionization-Time of Flight. A linear α-helical peptide with flexible termini (LLKELWTKMKGAGKAVLGKIKGLL) was found, corresponding to a previously described peptide from ant venom and here denominated as Bm-ponericin-L1. The antibacterial activity of Bm-ponericin-L1 was determined against ESKAPE pathogens. Scanning electron microscopy confirmed the membrane disruption potential of Bm-ponericin-L1. Moreover, this peptide also showed promising antibiofilm activity. Finally, cell viability and hemolytic assays revealed that Bm-ponericin-L1 is non-toxic toward primary fibroblasts cell lines and red blood cells, respectively. This study opens up new perspectives toward an alternative approach to overcoming multiple-antibiotic-resistance by means of AMPs through invertebrates' infection with human pathogenic bacteria.

Venomics of the Central European Myrmicine Ants Myrmica rubra and Myrmica ruginodis.

Animal venoms are a rich source of novel biomolecules with potential applications in medicine and agriculture. Ants are one of the most species-rich lineages of venomous animals. However, only a fraction of their biodiversity has been studied so far. Here, we investigated the venom components of two myrmicine (subfamily Myrmicinae) ants: Myrmica rubra and Myrmica ruginodis. We applied a venomics workflow based on proteotranscriptomics and found that the venoms of both species are composed of several protein classes, including venom serine proteases, cysteine-rich secretory protein, antigen 5 and pathogenesis-related 1 (CAP) superfamily proteins, Kunitz-type serine protease inhibitors and venom acid phosphatases. Several of these protein classes are known venom allergens, and for the first time we detected phospholipase A1 in the venom of M. ruginodis. We also identified two novel epidermal growth factor (EGF) family toxins in the M. ruginodis venom proteome and an array of additional EGF-like toxins in the venom gland transcriptomes of both species. These are similar to known toxins from the related myrmicine ant, Manica rubida, and the myrmecine (subfamily Myrmeciinae) Australian red bulldog ant Myrmecia gullosa, and are possibly deployed as weapons in defensive scenarios or to subdue prey. Our work suggests that M.rubra and M. ruginodis venoms contain many enzymes and other high-molecular-weight proteins that cause cell damage. Nevertheless, the presence of EGF-like toxins suggests that myrmicine ants have also recruited smaller peptide components into their venom arsenal. Although little is known about the bioactivity and function of EGF-like toxins, their presence in myrmicine and myrmecine ants suggests they play a key role in the venom systems of the superfamily Formicoidea. Our work adds to the emerging picture of ant venoms as a source of novel bioactive molecules and highlights the need to incorporate such taxa in future venom bioprospecting programs.

Shedding Lights on Crude Venom from Solitary Foraging Predatory Ant Ectatomma opaciventre: Initial Toxinological Investigation.

Some species of primitive predatory ants, despite living in a colony, exercise their hunting collection strategy individually; their venom is painful, paralyzing, digestive, and lethal for their prey, yet the toxins responsible for these effects are poorly known. Ectatomma opaciventre is a previously unrecorded solitary hunting ant from the Brazilian Cerrado. To overcome this hindrance, the present study performed the in vitro enzymatic, biochemical, and biological activities of E. opaciventre to better understand the properties of this venom. Its venom showed several proteins with masses ranging from 1-116 kDa, highlighting the complexity of this venom. Compounds with high enzymatic activity were described, elucidating different enzyme classes present in the venom, with the presence of the first L-amino acid oxidase in Hymenoptera venoms being reported. Its crude venom contributes to a state of blood incoagulability, acting on primary hemostasis, inhibiting collagen-induced platelet aggregation, and operating on the fibrinolysis of loose red clots. Furthermore, the E. opaciventre venom preferentially induced cytotoxic effects on lung cancer cell lines and three different species of Leishmania. These data shed a comprehensive portrait of enzymatic components, biochemical and biological effects in vitro, opening perspectives for bio-pharmacological application of E. opaciventre venom molecules.

Venenos animais como possíveis ferramentas terapéuticas contra o estresse oxidativo em diversas doengas: Revisao da Literatura / Animal venoms as possible therapeutic tools against oxidative stress in several diseases: Literature Review

Resumo Venenos sao uma substancia tóxica (composta por uma ou mais toxinas) que podem causando lesao fisiológica dependente da dose. As toxinas sao moléculas bioativas formadas principalmente por compostos enzimáticos e nao enzimático que porque provocam consequéncias indesejáveis nas presas, além disso, exibem atividades biológicas únicas, diversas e específicas que perturbam os processos fisiológicos normais. Entretanto, muitas toxinas, de diferentes animais, tém sido isoladas e muitas delas sao consideradas ótimas ferramentas para pesquisa básica e alvos terapéuticos. Foi relatado que o estresse oxidativo desempenha um papel fundamental na patogénese de várias doengas, como distúrbios neurodegenerativos, distúrbios cardiovasculares e cáncer. O mecanismo pelo qual as toxinas animais atuam nos parametros de estresse oxidativo em várias doengas, ainda nao está estabelecido. O foco principal desta revisao é destacar os principais estudos com toxinas animais como ferramenta terapéutica em diversas doengas, atuando no balango redox do organismo.

Abstract Venoms are a toxic substance (comprised of one or more toxins) that can cause dose-dependent physiological injury. Toxins are bioactive molecules formed primarily by enzymatic and non-enzymatic compounds that cause undesirable conse-quences in prey, in addition, exhibit unique, diverse and specific biological activities that disrupt normal physiological processes. However, many toxins, from different animals, have been isolated and many of them are considered great tools for basic research and therapeutic targets. Oxidative stress has been reported to play a key role in the pathogenesis of various diseases such as neurodegenerative disorders, cardiovascular disorders and cancer. How animal toxins act on oxidative stress parameters in several diseases is not yet established. The main focus of this review is to highlight the main studies with animal toxins as a therapeutic tool in several diseases, acting on the organism's redox balance.

Resumen Los venenos son sustancias tóxicas (compuestas por una o más toxinas) que pueden causar daño fisiológico dependiente de la dosis. Las toxinas son moléculas bioactivas formadas principalmente por compuestos enzimáticos y no enzimáticos que debido a que causan consecuencias indeseables en las presas, además, exhiben actividades biológicas únicas, diversas y específicas que alteran los procesos fisiológicos normales. Sin embargo, se han aislado muchas toxinas de diferentes animales, y muchos de ellos se consideran grandes herramientas para la investigación básica y dianas terapéuticas. Se ha informado que el estrés oxidativo juega un papel clave en la patogenia de diversas enfermedades, como los trastornos neurodegenerativos, enfermedades cardiovasculares y cáncer. El mecanismo por el cual las toxinas animales actúan sobre los parámetros de estrés oxidativo en vários enfermedades, aún no está establecido. El enfoque principal de esta revisión es resaltar los principales estudios con toxinas animales como herramienta terapéutica en diversas enfermedades, actuando en el equilibrio redox del organismo.

Multipurpose peptides: The venoms of Amazonian stinging ants contain anthelmintic ponericins with diverse predatory and defensive activities.

In the face of increasing drug resistance, the development of new anthelmintics is critical for controlling nematodes that parasitise livestock. Although hymenopteran venom toxins have attracted attention for applications in agriculture and medicine, few studies have explored their potential as anthelmintics. Here we assessed hymenopteran venoms as a possible source of new anthelmintic compounds by screening a panel of ten hymenopteran venoms against Haemonchus contortus, a major pathogenic nematode of ruminants. Using bioassay-guided fractionation coupled with liquid chromatography-tandem mass spectrometry, we identified four novel anthelmintic peptides (ponericins) from the venom of the neotropical ant Neoponera commutata and the previously described ponericin M-PONTX-Na1b from Neoponera apicalis venom. These peptides inhibit H. contortus development with IC50 values of 2.8-5.6 µM. Circular dichroism spectropolarimetry indicated that the ponericins are unstructured in aqueous solution but adopt α-helical conformations in lipid mimetic environments. We show that the ponericins induce non-specific membrane perturbation, which confers broad-spectrum antimicrobial, insecticidal, cytotoxic, hemolytic, and algogenic activities, with activity across all assays typically correlated. We also show for the first time that ponericins induce spontaneous pain behaviour when injected in mice. We propose that the broad-spectrum activity of the ponericins enables them to play both a predatory and defensive role in neoponeran ants, consistent with their high abundance in venom. This study reveals a broader functionality for ponericins than previously assumed, and highlights both the opportunities and challenges in pursuing ant venom peptides as potential therapeutics.

Mutualistic interaction of aphids and ants in pepper, Capsicum annuum and Capsicum frutenscens (Solanaceae) / Interacción mutualista de pulgones y hormigas en pimiento, Capsicum annuum y Capsicum frutenscens (Solanaceae)

Abstract Introduction: Adequate biological identification is fundamental for establishing integrated pest management programs and identifying the trophic and mutualist relationships that can affect pest population dynamics. Aphids are the main pest of pepper Capsicum spp. (Solanaceae) crops in Southwestern Colombia, due to their role as vectors of viruses. However, the identification of aphid species is complex, limiting the investigations performed to address their interactions with other organisms. Ants and aphids present a facultative mutualistic relationship, that promotes the growth of hemipteran colonies, for this reason, the study of the ecological mutualistic association between aphids and ants is important. Objective: The main objective was to discriminate the aphid species present in commercial crops of Capsicum spp., and to identify the ant community that attends the aphid colonies and its effects on the size of the aphid colonies. Methods: Aphid species, and their ant mutualist, were collected from Capsicum annuum and Capsicum frutescens, in the Cauca valley, Southwestern Colombia. We used the DNA barcoding approach to identify aphid species, and the ants were identified by morphology-based taxonomy. To evaluate the effect of ant care on the size and structure of aphid colonies, generalized linear models were calculated using as the response variables the total number of aphids for each colony and the proportion of nymphs. Results: The aphid species that attack pepper crops, are: Aphis gossypii and Myzus persicae (Hemiptera: Aphididae), with A. gossypii being the species that interacts with ants (19 ant species). A. gossypii colonies attended by ants had larger sizes and more nymphs per colony, than those not attended. Conclusions: Although the aphid-ant interaction is not species-specific, it is necessary to consider its role in the propagation of viral diseases in peppers and to determine how this interaction may affect regional biological control strategies.

Resumen Introducción: La adecuada identificación biológica es fundamental para establecer programas de manejo integrado de plagas e identificar las relaciones tróficas y mutualistas que pueden afectar la dinámica poblacional de insectos plaga. Los áfidos son las principales plagas del ají Capsicum spp. (Solanaceae) en el suroccidente colombiano, debido a su rol como vectores de virus. Sin embargo, su identificación es compleja, y limita las investigaciones que intentan revelar sus interacciones con otros organismos. Las hormigas y los áfidos presentan una relación mutualista facultativa, que promueve el crecimiento de las colonias de los hemípteros, por esta razón, el estudio de la asociación ecológica y mutualista entre áfidos y hormigas es importante. Objetivo: El principal objetivo de esta investigación fue discriminar las especies de áfidos presentes en cultivos comerciales de Capsicum spp., e identificar la comunidad de hormigas que atiende las colonias de áfidos y su efecto en el tamaño de las colonias de áfidos. Métodos: Los áfidos, y las hormigas mutualistas de estos áfidos, se recolectaron de Capsicum annuum y Capsicum frutescens, en el valle del rio Cauca, en el suroccidente colombiano. Se empleó el Código de barras del ADN para identificar las especies de áfidos, y las hormigas se identificaron empleando taxonomía basada en morfología. Para evaluar el efecto que tiene el cuidado de las hormigas sobre el tamaño de las colonias de áfidos, se empleó un modelo lineal generalizado, utilizando como variables de respuesta el número total de áfidos por cada colonia y la proporción de ninfas por colonia. Resultados: Las especies de áfidos que atacan los cultivos de ají, son: Aphis gossypii y Myzus persicae (Hemiptera: Aphididae), siendo A. gossypii la especie que interactúa con hormigas (19 especies). Las colonias de A. gossypii atendidas por hormigas presentan mayor tamaño y número de ninfas, que aquellas desatendidas. Conclusiones: Aunque la interacción áfido-hormiga no es especie específica, es necesario considerar su rol en la propagación de enfermedades virales en plantas cultivadas y determinar cómo esta interacción puede afectar la implementación de estrategias de control biológico.

Composition and Acute Inflammatory Response from Tetraponera rufonigra Venom on RAW 264.7 Macrophage Cells.

Tetraponera rufonigra (Arboreal Bicoloured Ant) venom induces pain, inflammation, and anaphylaxis in people and has an increased incident in Southeast Asia regions. The bioactive components and mechanism of action of the ant venom are still limited. The aim of this research was to identify the protein composition and inflammatory process of the ant venom by using RAW 264.7 macrophage cells. The major venom proteins are composed of 5' nucleotidase, prolyl endopeptidase-like, aminopeptidase N, trypsin-3, venom protein, and phospholipase A2 (PLA2). The venom showed PLA2 activity and represented 0.46 µg of PLA2 bee venom equivalent/µg crude venom protein. The venom induced cytotoxic in a dose- and time-dependent manner with IC20 approximately at 4.01 µg/mL. The increased levels of COX-2 and PGE2 were observed after 1 h of treatment correlating with an upregulation of COX-2 expression. Moreover, the level of mPGES-1 expression was obviously increased after 12 h of venom induction. Hence, our results suggested that the induction of COX-2/mPGEs-1 pathway could be a direct pathway for the ant venom-induced inflammation.

Samsum ant venom protects against carbon tetrachloride-induced acute spleen toxicity in vivo.

Many active molecules used in the development of new drugs are produced by ants. Present study assessed antioxidant and anti-inflammatory properties of Samsum ant venom (SAV) extract in carbon tetrachloride (CCL4)-induced spleen toxicity. Toxicity and oxidative stress were measured in four experimental groups: a negative control group without any treatment, a positive control group (CCl4-treated rats; a single dose of 1 ml/kg CCL4), an experimental group of CCl4-treated rats co-treated daily with SAV (100 µl), and a group to determine safe use with rats treated only with SAV (100 µl) daily for 3 weeks. CCl4-treatment led to an elevation in toxicity and oxidative stress. CCl4 significantly elevated malondialdehyde (MDA) levels, as well as expression of inhibitor of κB (IκB) and tumor necrosis factor-α (TNF-α) proteins. On the other hand, a decrease in glutathione (GSH) and catalase (CAT) levels were detected in CCl4-treated rats. Co-treatment with SAV was found to reduce these inflammatory and oxidative parameters. SAV elucidated a significant recovery of MDA concentration as well as a significant restoration in GSH levels compared to CCl4-treated rats; however, SAV increased CAT levels compared to normal rats. Hence, SAV was found to restore splenomegaly induced in CCl4-treated rats. Histopathological analysis also favored the biochemical analysis showing improvement in splenic architecture in CCl4 and SAV co-treated rats. The antioxidant properties of SAV may potentially enhance anti-inflammatory actions and improve spleen structure and function in CCl4-challenged rats.

Antimicrobial activity of synthetic Dq-3162, a 28-residue ponericin G-like dinoponeratoxin from the giant ant Dinoponera quadriceps venom, against carbapenem-resistant bacteria.

The predatory giant ant Dinoponera quadriceps is one of the largest venomous ants on Earth. The venom of D. quadriceps comprises a rich blend of bioactive peptides that includes structures related to at least five classes of antimicrobial peptides. In the present study, two representative synthetic peptides, sDq-2562 and sDq-3162, belonging to the ponericin-like dinoponeratoxin family, were evaluated for their microbicide activity against antibiotic-resistant bacteria. The most effective peptide, the 28-residue sDq-3162 displayed a significant bacteriostatic and bactericidal effect with minimal inhibitory concentrations (MICs) between 5 µM and 10 µM (15.6 µg mL-1 and 31.2 µg mL-1), according to the strain of drug-resistant bacteria tested. In combination with conventional antibiotics, sDq-3162 displayed in vitro synergistic effects, reducing the MICs of antibiotics for more than 2-log against clinical isolates of carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa, with low cytotoxicity to human erythrocytes, in vitro. Since the development of molecules to circumvent the spread of antibiotic-resistant bacteria is demanding, ant venom peptides arise as useful molecular resources to contribute with the antimicrobial arsenal and therapeutic strategies to fight clinically relevant microbial infections.