scholarly journals Loxosceles gaucho Spider Venom: An Untapped Source of Antimicrobial Agents

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 522 ◽  
Author(s):  
Paula Segura-Ramírez ◽  
Pedro Silva Júnior
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Antimicrobial Agents ◽  
Chemical Properties ◽  
Carcinoma Cells ◽  
Promising Candidate ◽  
Human Red Blood Cells ◽  
New Antibiotics ◽  
Conventional Antibiotics ◽  
Human Cervical Carcinoma Cells

The remarkable ability of microorganisms to develop resistance to conventional antibiotics is one of the biggest challenges that the pharmaceutical industry currently faces. Recent studies suggest that antimicrobial peptides discovered in spider venoms may be useful resources for the design of structurally new anti-infective agents effective against drug-resistant microorganisms. In this work, we found an anionic antibacterial peptide named U1-SCRTX-Lg1a in the venom of the spider Loxosceles gaucho. The peptide was purified using high-performance liquid chromatography (HPLC), its antimicrobial activity was tested through liquid growth inhibition assays, and its chemical properties were characterized using mass spectrometry. U1-SCRTX-Lg1a was found to show a monoisotopic mass of 1695.75 Da, activity against Gram-negative bacteria, a lack of hemolytic effects against human red blood cells, and a lack of cytotoxicity against human cervical carcinoma cells (HeLa). Besides this, the sequence of the peptide exhibited great similarity to specific regions of phospholipases D from different species of Loxosceles spiders, leading to the hypothesis that U1-SCRTX-Lg1a may have originated from a limited proteolytic cleavage. Our data suggest that U1-SCRTX-Lg1a is a promising candidate for the development of new antibiotics that could help fight bacterial infections and represents an exciting discovery for Loxosceles spiders.

scholarly journals The Design of Alapropoginine, a Novel Conjugated Ultrashort Antimicrobial Peptide with Potent Synergistic Antimicrobial Activity in Combination with Conventional Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 712
Author(s):  
Ali Salama ◽  
Ammar Almaaytah ◽  
Rula M. Darwish
Keyword(s):  
Antimicrobial Activity ◽  
Hemolytic Activity ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Resistant Bacteria ◽  
Human Red Blood Cells ◽  
Drug Resistant Bacteria ◽  
Different Strains ◽  
Conventional Antibiotics

(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.

scholarly journals Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Defense Mechanism ◽  
Treatment Options ◽  
Bacterial Biofilms ◽  
Host Immune System ◽  
New Antibiotics ◽  
Financial Burdens ◽  
Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

scholarly journals Investigation of the Biochemical and Ultrastructural Mechanisms Underlying the Antimicrobial Activity of Mimusops spp. Extracts

2020 ◽  
Vol 17 (2) ◽  
pp. 0452
Author(s):  
Mahmoud S.M. Mohamed ◽  
Gehad Abdelmohsen ◽  
Gouda T. M. Dawoud
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Antimicrobial Agents ◽  
Antimicrobial Effect ◽  
Inhibition Zone ◽  
Antibacterial Activities ◽  
Ultrastructural Changes ◽  
Bacterial Strains ◽  
Leaf Extracts ◽  
Traditional Medicines

Antibiotic resistance is the major growing threat facing the pharmacological treatment of bacterial infections. Therefore, bioprospecting the medicinal plants could provide potential sources for antimicrobial agents. Mimusops, the biggest and widely distributed plant genus of family Sapotaceae, is used in traditional medicines due to its promising pharmacological activities. This study was conducted to elucidate the antimicrobial effect of three unexplored Mimusops spp. (M. kummel, M. laurifolia and M. zeyheri). Furthermore, the mechanisms underlying such antibacterial activity were studied. The Mimusops leaf extracts revealed significant antibacterial activities against the five tested bacterial strains with a maximum inhibition zone diameter of 22.0 mm against B. subtilis compared with standard antibiotic ciprofloxacin. The minimal inhibitory and bactericidal concentration values against tested Gram-positive and Gram-negative bacterial strains ranged from 3.15-12.5 µg/ml. However, weak antifungal effect was recorded against Candida albicans with MIC value ˃25 µg/ml. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH) assay showed that M. caffra was the best antioxidant (IC50=14.75±0.028 µg/ml), while M. laurifolia was the least one (IC50=34.22±0.014 µg/ml). The phenolics in plant leaves extracts were identified and quantified by high performance liquid chromatography (HPLC) which revealed the presence of seven phenolic acids and four flavonoids. The abundant phenolic compounds were rutin (5.216±0.067 mg/g dried wt.) and gallic acid (0.296±0.068 mg/g) followed by myricetin (0.317±0.091 mg/g) then kaempferol (0.113±0.049 mg/g) as flavonoids. The antibacterial mechanism of M. laurifolia extract, as a representative species, induces ultrastructural changes in the model bacterium Staphylococcus aureus with cell wall and plasma membrane lysis as revealed by transmission electron microscopy. Overall, Mimusops species (M. laurifolia, M. kummel and M. zeyheri) are promising natural alternative sources for antimicrobial agents.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals Bacteriophage Structure, Classification, Assembly and Phage Therapy

2021 ◽  
Vol 18 (2) ◽  
pp. 239-250
Author(s):  
Nabanita Giri
Keyword(s):  
Bacterial Infections ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
The Other ◽  
Basic Knowledge ◽  
New Antibiotics ◽  
Associated Proteins ◽  
Conventional Antibiotics ◽  
And Function ◽  
Structure Configuration

Current emergence of multidrug resistance and limitations in the development of the new antibiotics has proposed the problem of treating bacterial infections more challenging. This scenario may lead to the fear of failure in treating the multidrug resistant (MDR) bacterial infections and fuelled the uses of bacteriophages as an alternative of the conventional antibiotics in the post antibiotic era.So it is very much essential to know about the details of phage life cycle, assembly of phage complete structure, configuration and function of phage associated proteins etc. Although phages have been discovered a century ego, detailed study about lytic phages are gaining more interest in global fight against MDR bacterial species. This review has highlighted the basic knowledge of bacteriophage with the past and present scenario of several clinical studies targeting the MDR bacterial species. On the other hand it also discussed about the other uses of phages except human clinical trials.

Preparation of Antibacterial Polypeptides with Different Topologies and Their Antibacterial Properties

2022 ◽  
Author(s):  
Xiaodan Wang ◽  
FangPing Yang ◽  
Huawei Yang ◽  
Xu Zhang ◽  
Haoyu Tang ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Antibacterial Properties ◽  
Conventional Antibiotics

Antimicrobial peptides (AMPs) are attractive antimicrobial agents used to combat bacterial infections and have been advanced to be one of the most promising alternatives to conventional antibiotics. They stand out...

Synergism between Host Defence Peptides and Antibiotics Against Bacterial Infections

2020 ◽  
Vol 20 (14) ◽  
pp. 1238-1263 ◽  
Author(s):  
Jiarui Li ◽  
Pablo Fernández-Millán ◽  
Ester Boix
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Adjuvant Activity ◽  
Biofilm Growth ◽  
Intracellular Target ◽  
Conventional Antibiotics ◽  
Available Information ◽  
Toxic Concentrations

Background: Antimicrobial resistance (AMR) to conventional antibiotics is becoming one of the main global health threats and novel alternative strategies are urging. Antimicrobial peptides (AMPs), once forgotten, are coming back into the scene as promising tools to overcome bacterial resistance. Recent findings have attracted attention to the potentiality of AMPs to work as antibiotic adjuvants. Methods: In this review, we have tried to collect the currently available information on the mechanism of action of AMPs in synergy with other antimicrobial agents. In particular, we have focused on the mechanisms of action that mediate the inhibition of the emergence of bacterial resistance by AMPs. Results and Conclusion: We find in the literature many examples where AMPs can significantly reduce the antibiotic effective concentration. Mainly, the peptides work at the bacterial cell wall and thereby facilitate the drug access to its intracellular target. Complementarily, AMPs can also contribute to permeate the exopolysaccharide layer of biofilm communities, or even prevent bacterial adhesion and biofilm growth. Secondly, we find other peptides that can directly block the emergence of bacterial resistance mechanisms or interfere with the community quorum-sensing systems. Interestingly, the effective peptide concentrations for adjuvant activity and inhibition of bacterial resistance are much lower than the required for direct antimicrobial action. Finally, many AMPs expressed by innate immune cells are endowed with immunomodulatory properties and can participate in the host response against infection. Recent studies in animal models confirm that AMPs work as adjuvants at non-toxic concentrations and can be safely administrated for novel combined chemotherapies.

scholarly journals Fagoterapia, alternativa para el control de las infecciones bacterianas. Perspectivas en Colombia

2014 ◽  
Vol 20 (1) ◽  
pp. 43
Author(s):  
Catalina Prada-Peñaranda ◽  
Angela-Victoria Holguin-Moreno ◽  
Andres-Fernando González-Barrios ◽  
Martha-Josefina Vives-Florez
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Food Contamination ◽  
Economic Losses ◽  
Human Consumption ◽  
Private Companies ◽  
Great Opportunity ◽  
New Antibiotics

Bacteria easily acquire resistance to antimicrobial agents; this reduces the number of effective antibiotics available to treat bacterial infections. Food contamination by bacteria also generates important economic losses and health risks. Products for human consumption must be free of antibiotics used in clinical treatments, and the control of bacteria with antimicrobials is strictly regulated; however, there is a lack of development of new antibiotics. As a result, the development of new antimicrobial strategies is vital. Viruses that infect bacteria called bacteriophages (phages) have been proposed as an alternative treatment in an approach known as phage-therapy. Several studies have evaluated and demonstrated their effectiveness against pathogenic bacteria; currently, there are private companies dedicated to the development of new products based on phage cocktails, to control some bacterial infections. In Colombia, there is no previous information about the use of phages, but phage-therapy represents a great opportunity to use the diversity of the native microbiota. In this review, we present the perspectives for phage-therapy in Colombia as a treatment against bacterial infections.

scholarly journals Clinically relevant infections in hematology and oncology: bacterial infections and the role of novel antibiotics in times of multidrug resistance

2021 ◽  
Author(s):  
Gernot Fritsche
Keyword(s):  
Multidrug Resistance ◽  
Antibiotic Therapy ◽  
Bacterial Infections ◽  
Empirical Therapy ◽  
Multidrug Resistant ◽  
Infectious Complications ◽  
Novel Drugs ◽  
New Antibiotics ◽  
Conventional Antibiotics ◽  
Novel Antibiotics

SummaryMultidrug resistance of bacterial pathogens is an increasing problem wordwide, especially treatment of multidrug resistant (MDR) gramnegative bacteria is challenging. In the recent past, several new antibiotics as well as new betalactamase inhibitors have been introduced. These novel drugs are valuable new tools for the therapy of infectious complications in cancer patients once there is a high risk for infections due to multidrug-resistant pathogens. While it is necessary to start empirical antibiotic therapy immediately, novel antibiotics only provide benefits in certain situations, depending on the underlying pathogens. Thus, these new antibiotics are best used guided by microbiological testing, since the exact mechanism of resistance determines susceptibility or resistance to certain antibiotics. For empirical therapy, previous culture results and/or colonization with MDR pathogens can help to choose from conventional antibiotics or novel drugs. In clinical practice, optimal antibiotic therapy can be achieved by close collaboration of specialists in hematooncology, infectious diseases and microbiology.

scholarly journals Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents

2022 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Davide Roncarati ◽  
Vincenzo Scarlato ◽  
Andrea Vannini
Keyword(s):  
Biological Activity ◽  
Antibiotic Treatment ◽  
Bacterial Infections ◽  
Scientific Community ◽  
Antimicrobial Agents ◽  
Modern Medicine ◽  
High Potential ◽  
New Drugs ◽  
New Antibiotics ◽  
New Compounds

Since the discovery of penicillin in the first half of the last century, antibiotics have become the pillars of modern medicine for fighting bacterial infections. However, pathogens resistant to antibiotic treatment have increased in recent decades, and efforts to discover new antibiotics have decreased. As a result, it is becoming increasingly difficult to treat bacterial infections successfully, and we look forward to more significant efforts from both governments and the scientific community to research new antibacterial drugs. This perspective article highlights the high potential of bacterial transcriptional and posttranscriptional regulators as targets for developing new drugs. We highlight some recent advances in the search for new compounds that inhibit their biological activity and, as such, appear very promising for treating bacterial infections.

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