scholarly journals Limacus flavus yellow slug: bioactive molecules in the mucus

2021 ◽  
Author(s):  
Patricia Yumi Hayashida ◽  
Pedro Ismael Silva Junior

Background: Snails and slugs were used as a treatment for many health problems therefore ancient times. Since the antimicrobial resistance became a major global thread, antimicrobial peptides have been considered as a potential source for development of new drugs, especially for drug-resistant bacteria. Nowadays reports confirm that the mucous secretions have antimicrobial, antiviral and antifungal properties. Methods: The present study has the objective to characterize and evaluate antimicrobial peptides of Limacus flavus mucus. The mucus was obtained by thermal shock and submitted to RP-HPLC. Fractions were used to perform the antimicrobial activity and hemolytic assays, electrophoresis (SDS-Page Gel) and submitted to mass spectrometry (LC-MS / MS). Identification and characterization was performed by PeaksX+ software. The physicochemical parameters were evaluated with bioinformatics tools, which predicted water solubility, iso-electric point, charge net and its primary structure. Results: Three fractions were isolated from the mucus of L. flavus and presented antifungal and antibacterial activity. The mucus showed greater inhibition for filamentous fungi (Aspergillus niger), yeast (Cryptococcus neoformans), Gram positive bacteria (Bacillus subtilis, Micrococcus luteus) and Gram negative bacteria (Enterobacter cloacae). These fractions also did not show hemolytic activity for human blood cells (erythrocytes). Fractions sequences were identified and presents Mw <3kDa, WLGH, DLQW, YLRW, respectively. Conclusion: This study revealed three antimicrobial peptides of L. flavus mucus with a wide range of antimicrobial activity and its physic-chemical characterization. Keywords: Limacus flavus, mucus, slug, antimicrobial peptide, bioactive molecules, resistance, microorganisms.

2021 ◽  
Author(s):  
Alvin Hu

BACKGROUND Cationic antimicrobial peptides have broad antimicrobial activity and provide a novel way of targeting multi drug resistant bacteria in an era of increasing antimicrobial resistance. Current developments show positive prospects for both antimicrobial peptides and silver nanoparticles individually. OBJECTIVE The primary objective is to propose another method of enhancing antimicrobial activity by conjugating silver nanoparticles with cationic antimicrobial peptides for a subsequent preliminary assessment on studying the minimum inhibitory concentration of multi drug resistant bacteria. The secondary objective would be to evaluate the safety of the conjugated compound to assess viability for in vivo use. METHODS The proposition is planned for approximately 3 overarching stages. Firstly, I propose synthesis of wlbu2c, a modified version of antimicrobial peptide wlbu2 with an added cysteine group, using standard Fmoc procedure. This will subsequently be attempted to stably conjugate with silver nanoparticles ideally through photochemical means. Secondly, the conjugate wlbu2c-AgNP will be tested for antimicrobial activity following Clinical & Laboratory Standards Institute Manual on standard minimum inhibitory concentration testing. If all of the above is completed the experiment can progress to the assessment of cytotoxicity using cell lysis assays. RESULTS I-TASSER simulation revealed that our modified peptide wlbu2c has similar secondary structure to original wlbu2 peptide. No other results have been obtained at this time other than aforementioned theoretical propositions. CONCLUSIONS The addition of silver nanoparticles to already developing de novo engineered antimicrobial peptides provide a second degree of freedom toward the development of potent antimicrobials. Future prospects include emergency last line therapy, treatment for current difficult to eradicate bacterial colonization such as in cystic fibrosis, implantable medical devices, cancer and immunotherapy. This proposal is intended to be provided to the public as I do not anticipate funding at this time.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rong Tan ◽  
Meiru Wang ◽  
Huiqin Xu ◽  
Lu Qin ◽  
Jun Wang ◽  
...  

With the increasing number of drug-resistant bacteria, there is an urgent need for new antimicrobial agents, and antimicrobial peptides (AMPs), which exist in the human non-specific immune system, are one of the most promising candidates. It is an effective optimization strategy to modify antimicrobial peptides (AMPs) according to the distribution of amino acids and hydrophobic characteristics. The addition of bacterial pheromones to the N short peptide can increase the ability to recognize bacteria. In this study, we designed and synthesized AMP1–6 by amino acid substitution of mBjAMP1. Additionally, P-6, S-6, and L-6 were designed and synthesized by adding bacterial pheromones based on 1–6. Functional tests showed that the four AMPs had the ability to kill Gram-negative Vibrio anguillarum, Pseudomonas mendocina, and Vibrio parahaemolyticus, and Gram-positive Micrococcus luteus and Listeria monocytogenes. Additionally, all four AMPs induced permeabilization and depolarization of bacterial cell membranes and increased intracellular reactive oxygen species (ROS) levels. Importantly, they had little or no mammalian cytotoxicity. At the same time, 1–6 and L-6 protected the stability of intestinal flora in Sebastes schlegelii and increased the relative abundance of Lactobacillaceae. In summary, our results indicate that the designed AMPs have broad application prospects as a new type of polypeptide antimicrobial agent.


2021 ◽  
Vol 11 (12) ◽  
pp. 5352
Author(s):  
Ana Margarida Pereira ◽  
Diana Gomes ◽  
André da Costa ◽  
Simoni Campos Dias ◽  
Margarida Casal ◽  
...  

Antibacterial resistance is a major worldwide threat due to the increasing number of infections caused by antibiotic-resistant bacteria with medical devices being a major source of these infections. This suggests the need for new antimicrobial biomaterial designs able to withstand the increasing pressure of antimicrobial resistance. Recombinant protein polymers (rPPs) are an emerging class of nature-inspired biopolymers with unique chemical, physical and biological properties. These polymers can be functionalized with antimicrobial molecules utilizing recombinant DNA technology and then produced in microbial cell factories. In this work, we report the functionalization of rPBPs based on elastin and silk-elastin with different antimicrobial peptides (AMPs). These polymers were produced in Escherichia coli, successfully purified by employing non-chromatographic processes, and used for the production of free-standing films. The antimicrobial activity of the materials was evaluated against Gram-positive and Gram-negative bacteria, and results showed that the polymers demonstrated antimicrobial activity, pointing out the potential of these biopolymers for the development of new advanced antimicrobial materials.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 712
Author(s):  
Ali Salama ◽  
Ammar Almaaytah ◽  
Rula M. Darwish

(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.


2016 ◽  
Vol 42 (2-3) ◽  
pp. 429-450 ◽  
Author(s):  
Thomas J. Hwang ◽  
Aaron S. Kesselheim

Accelerating the development and approval of novel therapeutics has emerged as a key public health priority given the mortality, morbidity, and economic costs associated with infections caused by drug-resistant bacteria. However, there is limited empirical evidence to guide policymaking, such as the factors that may disadvantage antibiotics compared to other classes of drugs. In this Article, we empirically examine characteristics of the key clinical trials underpinning FDA's approval of antibiotics and other drugs over the past decade. Despite perceptions that antibiotic trials are larger and more difficult to conduct, we find that antibiotic trials are no larger than those conducted for drugs approved in other disease areas with high unmet medical needs, suggesting that policymakers may need to target other levers to meaningfully stimulate innovation. We discuss the risks and benefits of harnessing new and existing regulatory pathways to speed the approval of new drugs, particularly those intended to treat patients with serious and life-threatening infections, and we evaluate ways that proposals for new regulatory pathways could be improved to better prioritize and expedite the approval of therapies with the greatest potential for patient health benefits.


2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong

Antimicrobial peptides (AMPs) have emerged as promising alternatives of traditional antibiotics against drug-resistant bacteria owing to their broad-spectrum antimicrobial properties and low tendency to drugresistance. However, their therapeutic efficacy in vivo, especially for infections in deep organs, is limited owing to their systemic toxicity and low bioavailability. Nanoparticles-based delivery systems offer a strategy to increase the therapeutic index of AMPs by preventing proteolysis, increasing the accumulation at infection sites, and reducing toxicity. Herein, we will discuss the current progress of using nanoparticles as delivery vehicles for AMPs for the treatment of deep infections.


2020 ◽  
Vol 21 (16) ◽  
pp. 5773 ◽  
Author(s):  
Surajit Bhattacharjya ◽  
Suzana K. Straus

In an era where the pipeline of new antibiotic development is drying up, the continuous rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria are genuine threats to human health. Although antimicrobial peptides (AMPs) may serve as promising leads against drug resistant bacteria, only a few AMPs are in advanced clinical trials. The limitations of AMPs, namely their low in vivo activity, toxicity, and poor bioavailability, need to be addressed. Here, we review engineering of frog derived short α-helical AMPs (aurein, temporins) and lipopolysaccharide (LPS) binding designed β-boomerang AMPs for further development. The discovery of novel cell selective AMPs from the human proprotein convertase furin is also discussed.


Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Guizi Ye ◽  
Hongyu Wu ◽  
Jinjiang Huang ◽  
Wei Wang ◽  
Kuikui Ge ◽  
...  

Abstract Antimicrobial peptides (AMPs) have been regarded as a potential weapon to fight against drug-resistant bacteria, which is threating the globe. Thus, more and more AMPs had been designed or identified. There is a need to integrate them into a platform for researchers to facilitate investigation and analyze existing AMPs. The AMP database has become an important tool for the discovery and transformation of AMPs as agents. A database linking antimicrobial peptides (LAMPs), launched in 2013, serves as a comprehensive tool to supply exhaustive information of AMP on a single platform. LAMP2, an updated version of LAMP, holds 23 253 unique AMP sequences and expands to link 16 public AMP databases. In the current version, there are more than 50% (12 236) sequences only linking a single database and more than 45% of AMPs linking two or more database links. Additionally, updated categories based on primary structure, collection, composition, source and function have been integrated into LAMP2. Peptides in LAMP2 have been integrated in 8 major functional classes and 38 functional activities. More than 89% (20 909) of the peptides are experimentally validated peptides. A total of 1924 references were extracted and regarded as the evidence for supporting AMP activity and cytotoxicity. The updated version will be helpful to the scientific community.


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