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

Abstract

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.

Functional and Proteomic Insights into Aculeata Venoms

“…In order to fully characterize the venoms of aculeates, a comparative study of venomgland transcriptomes and proteomes is necessary. In recent years, the number of studies that included these data for hymenopterans has increased, but in the face of the enormous diversity of the order, it is clear that the research community has only started to scratch the surface of what there is to be discovered [ 62 , 78 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ]. One interesting aspect of our own contribution to this enormous task is that the transcripts we identified from the venom gland of A. mellifera were found to have nearly identical sequences to other A. mellifera venom proteins which are available in the Uniprot database ( Figure 2 ) and those identified by Koludarov et al [ 78 ].…”

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

“…The venom composition of ants has received less attention with limited publication to date [ 10 , 11 , 12 , 13 , 14 ]. These previously published studies revealed the large diversity of venom components from each species based on the transcriptomic, proteomic, or proteo-transcriptomic approach [ 10 , 13 , 20 , 21 ].…”

“…Until recently, alkaloids in the venom of ants have been relatively well-studied [ 9 ], while other venomous chemical compounds and proteinaceous venoms remain largely unveiled. Proteinaceous venom components have only been deciphered in a limited number of ants from several subfamilies including Ectatomminae, Myrmeciinae, Myrmicinae, Ponerinae, Paraponerinae, and Pseudomyrmecinae, mostly focused on emblematic species [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. The characterization of venom components from more ant species belonging to diverse subfamilies will contribute to a better understanding of the evolution of ant venoms and facilitate their applications.…”

Venom biotechnology: casting light on nature’s deadliest weapons using synthetic biology

“…For example, thanks to the high sensitivity of modern methods, venom components can now be analyzed using limited amounts of sample material. This has allowed the inclusion of species that were formerly either too rare for the collection of meaningful amounts of venom, or too small to deliver sufficient venom yields ( de Graaf et al, 2009 ; Bouzid et al, 2014 ; Lewis Ames et al, 2016 ; Walker et al, 2018 ; Walker et al, 2021 ; Casewell et al, 2019 ; Krämer et al, 2019 ; Schmidt et al, 2019 ; Lüddecke et al, 2020 ; Lüddecke et al, 2022 ; Hurka et al, 2022 ; von Reumont et al, 2022 ).…”