The advent of multidrug resistance among pathogenic bacteria has attracted great attention worldwide. As a response to this growing challenge, diverse studies have focused on the development of novel anti-infective therapies, including antimicrobial peptides (AMPs). The biological properties of this class of antimicrobials have been thoroughly investigated, and membranolytic activities are the most reported mechanisms by which AMPs kill bacteria. Nevertheless, an increasing number of works have pointed to a different direction, in which AMPs are seen to be capable of displaying non-lytic modes of action by internalizing bacterial cells. In this context, this review focused on the description of the in vitro and in vivo antibacterial and antibiofilm activities of non-lytic AMPs, including indolicidin, buforin II PR-39, bactenecins, apidaecin, and drosocin, also shedding light on how AMPs interact with and further translocate through bacterial membranes to act on intracellular targets, including DNA, RNA, cell wall and protein synthesis.

Bacterial infections caused by intracellular pathogens are difficult to control. Conventional antibiotic therapies are often ineffective, as high doses are needed to increase the number of antibiotics that will cross the host cell membrane to act on the intracellular bacterium. Moreover, higher doses of antibiotics may lead to elevated severe toxic effects against host cells. In this context, antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) have shown great potential to treat such infections by acting directly on the intracellular pathogenic bacterium or performing the delivery of cargos with antibacterial activities. Therefore, in this mini-review, we cover the main AMPs and CPPs described to date, aiming at intracellular bacterial infection treatment. Moreover, we discuss some of the proposed mechanisms of action for these peptide classes and their conjugation with other antimicrobials.

Antimicrobial peptides (AMPs) represent alternative strategies to combat the global health problem of antibiotic resistance. However, naturally occurring AMPs are generally not sufficiently active for use as antibiotics. Optimized synthetic versions incorporating additional design principles are needed. Here, we engineered amino-terminal Cu(II) and Ni(II) (ATCUN) binding motifs, which can enhance biological function, into the native sequence of two AMPs, CM15 and citropin1.1. The incorporation of metalbinding motifs modulated the antimicrobial activity of synthetic peptides against a panel of carbapenem-resistant enterococci (CRE) bacteria, including carbapenem-resistant Klebsiella pneumoniae (KpC+) and Escherichia coli (KpC+). Activity modulation depended on the type of ATCUN variant utilized. Membrane permeability assays revealed that the in silico selected lead template, CM15, and its ATCUN analogs increased bacterial cell death. Mass spectrometry, circular dichroism, and molecular dynamics simulations indicated that coordinating ATCUN derivatives with Cu(II) ions did not increase the helical tendencies of the AMPs. CM15 ATCUN variants, when combined with Meropenem, streptomycin, or chloramphenicol, showed synergistic effects against E. coli (KpC+ 1812446) biofilms. Motif addition also reduced the hemolytic activity of the wild-type AMP and improved the survival rate of mice in a systemic infection model. The dependence of these bioactivities on the particular amino acids of the ATCUN motif highlights the possible use of size, charge, and hydrophobicity to fine-tune AMP biological function. Our data indicate that incorporating metal-binding motifs into peptide sequences leads to synthetic variants with modified biological properties. These principles may be applied to augment the activities of other peptide sequences.

In recent decades, cancer and multidrug resistance have become a worldwide problem, resulting in high morbidity and mortality. Some infectious agents like Streptococcus pneumoniae , Stomatococcus mucilaginous, Staphylococcus spp. , E. coli. Klebsiella spp. , Pseudomonas aeruginosa, Candida spp., Helicobacter pylori , hepatitis B and C, and human papillomaviruses (HPV) have been associated with the development of cancer. Chemotherapy, radiotherapy and antibiotics are the conventional treatment for cancer and infectious disease. This treatment causes damage in healthy cells and tissues, and usually triggers systemic side-effects, as well as drug resistance. Therefore, the search for new treatments is urgent, in order to improve efficacy and also reduce side-effects. Proteins and peptides originating from bacteria can thus be a promising alternative to conventional treatments used nowadays against cancer and infectious disease. These molecules have demonstrated specific activity against cancer cells and bacterial infection; indeed, proteins and peptides can be considered as future antimicrobial and anticancer drugs. In this context, this review will focus on the desirable characteristics of proteins and peptides from bacterial sources that demonstrated activity against microbial infections and cancer, as well as their efficacy in vitro and in vivo .

AMPs produced by B. mori induced by microbial challenge in the fat body.

The macauba palm (Acrocomia aculeata) is native of tropical America and is found mostly in the Cerrados and Pantanal biomes. The fruits provide an oily pulp, rich in long chain fatty acids, and a kernel that encompass more than 50% of lipids rich in medium chain fatty acids (MCFA). Based on biochemical and nutritional evidences MCFA is readily catabolized and can reduce body fat accumulation. In this study, an animal model was employed to evaluate the effect of Acrocomia aculeata kernel oil (AKO) on the blood glucose level and the fatty acid deposit in the epididymal adipose tissue. The A. aculeata kernel oil obtained by cold pressing presented suitable quality as edible oil. Its fatty acid profile indicates high concentration of MCFA, mainly lauric, capric and caprilic. Type 2 diabetic rats fed with that kernel oil showed reduction of blood glucose level in comparison with the diabetic control group. Acrocomia aculeata kernel oil showed hypoglycemic effect. A small fraction of total dietary medium chain fatty acid was accumulated in the epididymal adipose tissue of rats fed with AKO at both low and high doses and caprilic acid did not deposit at all.

O medicamento é essecial para o tratamento de várias patologias.

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