Production of a novel recombinant brown spider hyaluronidase in baculovirus-infected insect cells

De-Bona, Elidiana; Chaves-Moreira, Daniele; Batista, Thiago Beltrami Dias; Justa, Hanna Câmara da; Rossi, Gustavo Rodrigues; Antunes, Bruno César; Matsubara, Fernando Hitomi; Minozzo, João Carlos; Wille, Ana Carolina Martins; Veiga, Sílvio Sanches; Senff‐Ribeiro, Andrea; Gremski, Luiza Helena

doi:10.1016/j.enzmictec.2021.109759

Cited by 6 publications

(9 citation statements)

References 47 publications

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“…The sera of horses that received only rCpLi on immunizations performed around 50% of reduction in dermonecrosis (Figueiredo et al, 2014). As mentioned earlier, loxoscelic venoms have other proteins that play a role in loxoscelism, i.e., metalloproteinases, serine proteases, hyaluronidases, TCTP and allergens (Feitosa et al, 1998;Veiga et al, 2000;Da Silveira et al, 2007;Trevisan-Silva et al, 2010;Ferrer et al, 2013;Justa et al, 2020;De-Bona et al, 2021). Thus, the inclusion of these toxins in the production of sera turns out to be a strategy to enhance the efficacy of antivenoms.…”

Section: Systemic Injury (Main) and Cutaneous Lesionmentioning

confidence: 94%

“…Figure 1 illustrate this potential of such toxins. Moreover, a hyaluronidase (LiHyal2) and an allergen (LALLT) from L. intermedia venom were recombinantly expressed and may be used to enhance the range of antigens for antivenom production (Justa et al, 2020;De-Bona et al, 2021).…”

Section: Systemic Injury (Main) and Cutaneous Lesionmentioning

confidence: 99%

“…Venom hyaluronidases have been studied as purified enzymes (Poh et al, 1992;Girish et al, 2004;Morey et al, 2006;Horta et al, 2014) or as recombinant proteins mainly expressed in insect cells (Soldatova et al, 2007;Clement et al, 2012;De-Bona et al, 2021). In Loxosceles spider venoms, hyaluronidase activity was identified in six Loxosceles species (L. rufescens, L. deserta, L. gaucho, L. intermedia, L. laeta and L. reclusa) and some of these results were confirmed by subsequent proteome and transcriptome studies that described hyaluronidases or coding sequences for such enzymes in various Loxosceles venoms (Young and Pincus, 2001;Barbaro et al, 2005;Fernandes-Pedrosa et al, 2008;Dos Santos et al, 2009;Gremski et al, 2010;Trevisan-Silva et al, 2017;Siqueira et al, 2019).…”

Section: Hyaluronidases: Adjuvants To Enhance the Diffusion Of Other Drugs And Agents To Correct Esthetic Filling Proceduresmentioning

confidence: 99%

“…General data acquired from venom gland transcriptomes and venom proteomes elucidated the toxins' expression profile of many Loxosceles species (Machado et al, 2005;Fernandes-Pedrosa et al, 2008;Dos Santos et al, 2009;Gremski et al, 2010;Trevisan-Silva et al, 2017;Calabria et al, 2019). In addition, these screening efforts allowed the description of coding sequences of less expressed toxins, which enabled the production of these molecules as recombinant proteins (Sade et al, 2012;Ferrer et al, 2013;Graeff et al, 2019;Justa et al, 2020;De-Bona et al, 2021). In fact, some toxins, such as wild-type and mutated/inactive phospholipases D and astacin-like metalloproteases were recombinantly expressed before the first screening reports (Fernandes Pedrosa et al, 2002;Kalapothakis et al, 2002;Chaim et al, 2006;Da Silveira et al, 2007;Kusma et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Recombinant chimeric proteins consisting of Loxosceles toxins' epitopes were also produced (Mendes et al, 2013;Lima et al, 2018;Souza et al, 2018;Calabria et al, 2019). The expression model differs for each recombinant Loxosceles toxin since some of them are produced as soluble and active proteins by prokaryotic expression systems, while others require a more complex model to achieve the desired production protocol (Boia-ferreira et al, 2019;Graeff et al, 2019;Gremski et al, 2020;Justa et al, 2020;De-Bona et al, 2021). As the purification of toxins from Brown spider venoms usually yields tiny amounts of proteins, the production of recombinant toxins allowed their further characterization.…”

Section: Introductionmentioning

confidence: 99%

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Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs

Gremski

Matsubara

Polli

et al. 2021

Front. Mol. Biosci.

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Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.

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