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.
We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in health and disease via the activity of the gut-brain axis, possibly contributing to autism spectrum disorders, Alzheimer's disease, Parkinson's disease, depression, and anxiety disorder. Gut microbes may also be involved in nociception, complex host behaviors, and brain development. Future efforts will be needed to determine whether the observed associations correspond to causative mechanisms, as well as to engineer effective interventions to modulate the effects of the microbiome on the central nervous system.
Bacterial resistance is a major threat to plant crops, animals and human health, and over the years this situation has increasingly spread worldwide. Due to their many bioactive compounds, plants are promising sources of antimicrobial compounds that can potentially be used in the treatment of infections caused by microorganisms. As well as stem, flowers and leaves, fruits have an efficient defense mechanism against pests and pathogens, besides presenting nutritional and functional properties due to their multifunctional molecules. Among such compounds, the antimicrobial peptides (AMPs) feature different antimicrobials that are capable of disrupting the microbial membrane and of acting in binding to intra-cytoplasmic targets of microorganisms. They are therefore capable of controlling or halting the growth of microorganisms. In summary, this review describes the major classes of AMPs found in fruits, their possible use as biotechnological tools and prospects for the pharmaceutical industry and agribusiness.
Biofilm-forming bacteria may be 10−1000 times more resistant to antibiotics than planktonic bacteria and represent about 75% of bacterial infections in humans. Antibiofilm treatments are scarce, and no effective therapies have been reported so far. In this context, antibiofilm peptides (ABPs) represent an exciting class of agents with potent activity against biofilms both in vitro and in vivo. Moreover, murine models of bacterial biofilm infections have been used to evaluate the in vivo effectiveness of ABPs. Therefore, here we highlight the translational potential of ABPs and provide an overview of the different clinically relevant murine models to assess ABP efficacy, including wound, foreign body, chronic lung, and oral models of infection. We discuss key challenges to translate ABPs to the clinic and the pros and cons of the existing murine biofilm models for reliable assessment of the efficacy of ABPs.
Objectives
The number of bacterial pathogens resistant to the currently available antibiotics has dramatically increased, with antimicrobial peptides (AMPs) being among the most promising potential new drugs. In this study, the applicability and mechanisms of action of Pa-MAP 2 and Pa-MAP 1.9, two AMPs synthetically designed based on a natural AMP template, were evaluated.
Methods
Pa-MAP 2 and Pa-MAP 1.9 were tested against a clinically isolated multidrug-resistant (MDR) Escherichia coli strain. Biophysical approaches were used to evaluate the preference of both peptides for specific lipid membranes, and bacterial surface changes imaged by atomic force microscopy (AFM). The efficacy of both peptides was assessed both in vitro and in vivo.
Results
Experimental results showed that both peptides have antimicrobial activity against the E. coli MDR strain. Zeta potential and surface plasmon resonance assays showed that they interact extensively with negatively charged membranes, changing from a random coil structure, when free in solution, to an α-helical structure after membrane interaction. The antibacterial efficacy was evaluated in vitro, by several techniques, and in vivo, using a wound infection model, showing a concentration-dependent antibacterial effect. Different membrane properties were evaluated to understand the mechanism underlying peptide action, showing that both promote destabilization of the bacterial surface, as imaged by AFM, and change properties such as membrane surface and dipole potential.
Conclusions
Despite their similarity, data indicate that the mechanisms of action of the peptides are different, with Pa-MAP 1.9 being more effective than Pa-MAP 2. These results highlight their potential use as antimicrobial agents against MDR bacteria.
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