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.
Highlights
One of the main goals of modern medicine is the search for new antimicrobials, since outbreaks of extremely resistant bacteria are becoming more common
Since antimicrobial peptides mode of action are directly related with their secondary structure, for further structural homology analysis, its amino acid sequence was submitted to a bioinformatic program, the PSIPRED (Version 4.01, London, UK, 2016) online tool [22], and two alpha-helices were predicted (Figure 1B)
Since many of the homologue antimicrobial peptides (AMPs) do not have a three-dimensional structure deposited in the data bank, the ToAP2 structure was established with a similar sequence to other proteins
Summary
One of the main goals of modern medicine is the search for new antimicrobials, since outbreaks of extremely resistant bacteria are becoming more common. Toxins 2018, 10, 219 earlier described as causing infections related to outbreaks mainly associated with skin and soft tissue infections [2,3] This infection profile changed, as described by Sfeir et al (2018), and nowadays infections occurring in the respiratory tract have become the most worrisome cases [4]. The bacteria of this complex have resistance profiles to glutaraldehyde, widely used for disinfection in hospitals, as well as resistance to the main antimicrobial agents used to treat tuberculosis [3]. AMPs are present in several species of different kingdoms, for example, in snake [10], wasp [11], bee [12], and scorpion venoms [13], and have demonstrated action against several microorganisms, including human pathogens
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