Antimicrobial and Chemotactic Activity of Scorpion-Derived Peptide, ToAP2, against Mycobacterium massiliensis

Abstract

Mycobacterium massiliense is a rapid growing, multidrug-resistant, non-tuberculous mycobacteria that is responsible for a wide spectrum of skin and soft tissue infections, as well as other organs, such as the lungs. Antimicrobial peptides had been described as broad-spectrum antimicrobial, chemotactic, and immunomodulator molecules. In this study we evaluated an antimicrobial peptide derived from scorpion Tityus obscurus as an anti-mycobacterial agent in vitro and in vivo. Bioinformatics analyses demonstrated that the peptide ToAP2 have a conserved region similar to several membrane proteins, as well as mouse cathelicidin. ToAP2 inhibited the growth of four M. massiliense strains (GO01, GO06, GO08, and CRM0020) at a minimal bactericidal concentration (MBC) of 200 µM. MBC concentration used to treat infected macrophages was able to inhibit 50% of the bacterial growth of all strains. ToAP2 treatment of infected mice with bacilli reduced the bacterial load in the liver, lung, and spleen, similarly to clarithromycin levels (90%). ToAP2 alone recruited monocytes (F4/80low Gr1), neutrophils (F4/80− Gr1), and eosinophils (F4/80+ Gr1+). ToAP2, together with M. massiliense infection, was able to increase F4/80low and reduce the percentage of F4/80high macrophages when compared with infected and untreated mice. ToAP2 has in vitro anti-microbial activity that is improved in vivo due to chemotactic activity.

Dissecting Toxicity: The Venom Gland Transcriptome and the Venom Proteome of the Highly Venomous Scorpion Centruroides limpidus (Karsch, 1879)

“…CliHDPND401 has similarity to ToAP2 (A0A1D3IXJ5), a transcript isolated from the venom of Tityus obscurus . Synthetic ToAP2 displayed antimicrobial activity, both in vitro and in vivo [66]. CliHDPND402 is similar to peptide TsAP2 (S6D3A7), an antibacterial, antifungal, anticancer, and hemolytic peptide isolated from T. serrulatus [61].…”

Antiretroviral and cytotoxic activities of Tityus obscurus synthetic peptide

“…Clear signs of the late apoptosis stage or necrosis (Annexin + /PI + ) were observed among SIV-infected cells previously treated with P6 or AZT and less significantly among uninfected cells treated with P6 (Figure 8b). HUT-78 cells in the early stage of apoptosis were found among SIV-infected cells previously treated with P6 or AZT, which were also less pronounced in uninfected cells previously treated with AZT, even though uninfected cells treated with high P6 concentration showed signs of early stages of apoptosis (Figure 8c Marques-Neto et al [27] found that the same P6, reported as ToAP2, exhibited an antibacterial activity by signaling chemotactic activity to phagocytosis and sequentially destroying Mycobacterium massiliense in vivo and in vitro systems. Also, Guilhelmelli et al [28] reported in vitro activity against Cryptococcus neoformans and Candida albicans.…”

“…According to the bioinformatics analysis, [27] the ToAP2, referred here as P6, has conserved regions, similar to cell membrane proteins, as well as the mouse antimicrobial peptide (AMP) cathelicidin. These AMPs exhibit their activity by disrupting the cell membrane integrity.…”

Looking beyond Typical Treatments for Atypical Mycobacteria

“…Several reports have described the capacity of AMP to kill or inhibit the growth of NTM, including M. avium, M. abscessus, M. chelonae, M. marinum, M. fortuitum, M. massiliense, and M. kansasii (Table 3). These peptides come from diverse sources, going from bacteriocins (produced by bacteria) [161][162][163][164][165][166] to mammalian peptides like cathelicidins, human neutrophil peptide (α-defensins), and lactoferricin [167][168][169][170][171], but also including invertebrates like clams and arthropods [172][173][174][175][176]. Nonetheless, as happens for other new treatments, most of these studies are mainly directed towards Mtb, and the experimental use of NTM is often a way to overcome biosafety and experimental problems, or to address the peptides' activity spectrum.…”