scholarly journals Engineered Cationic Antimicrobial Peptides To Overcome Multidrug Resistance by ESKAPE Pathogens

2014 ◽  
Vol 59 (2) ◽  
pp. 1329-1333 ◽  
Author(s):  
Berthony Deslouches ◽  
Jonathan D. Steckbeck ◽  
Jodi K. Craigo ◽  
Yohei Doi ◽  
Jane L. Burns ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Antimicrobial Peptides ◽  
De Novo ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Clinical Settings ◽  
Eskape Pathogens ◽  
Antibiotic Peptides

ABSTRACTMultidrug resistance constitutes a threat to the medical achievements of the last 50 years. In this study, we demonstrated the abilities of twode novoengineered cationic antibiotic peptides (eCAPs), WLBU2 and WR12, to overcome resistance from 142 clinical isolates representing the most common multidrug-resistant (MDR) pathogens and to display a lower propensity to select for resistant bacteriain vitrocompared to that with colistin and LL37. The results warrant an exploration of eCAPs for use in clinical settings.

scholarly journals Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 501 ◽  
Author(s):  
Berthony Deslouches ◽  
Ronald C. Montelaro ◽  
Ken L. Urish ◽  
Yuanpu P. Di
Keyword(s):  
Antimicrobial Peptides ◽  
De Novo ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Health Crisis ◽  
Test Conditions ◽  
Reduced Activity

The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

Action mechanism of melittin-derived antimicrobial peptides, MDP1 and MDP2, de novo designed against multidrug resistant bacteria

Amino Acids ◽  
2018 ◽  
Vol 50 (9) ◽  
pp. 1231-1243 ◽  
Author(s):  
Reza Akbari ◽  
Mojdeh Hakemi Vala ◽  
Ali Hashemi ◽  
Hossein Aghazadeh ◽  
Jean-Marc Sabatier ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
De Novo ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Action Mechanism ◽  
Multidrug Resistant Bacteria

scholarly journals AMPing up the search: An in silico approach to identifying Antimicrobial Peptides (AMPs) with potential anti-biofilm activity

2021 ◽  
Author(s):  
Shreeya Mhade ◽  
Stutee Panse ◽  
Gandhar Tendulkar ◽  
Rohit Awate ◽  
Snehal Kadam ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
In Silico ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
C Protein ◽  
Pilus Biogenesis ◽  
Natural And Synthetic

AbstractAntibiotic resistance is a public health threat, and the rise of multidrug-resistant bacteria, including those that form protective biofilms, further compounds this challenge. Antimicrobial peptides (AMPs) have been recognized for their anti-infective properties, including their ability to target processes important for biofilm formation. However, given the vast array of natural and synthetic AMPs, determining potential candidates for anti-biofilm testing is a significant challenge. In this study, we present an in silico approach, based on open-source tools, to identify AMPs with potential anti-biofilm activity. This approach is developed using the sortase-pilin machinery, important for adhesion and biofilm formation, of the multidrug-resistant, biofilm-forming pathogen C. striatum as the target. Using homology modeling, we modeled the structure of the C. striatum sortase C protein, resembling the semi-open lid conformation adopted during pilus biogenesis. Next, we developed a structural library of 5544 natural and synthetic AMPs from sequences in the DRAMP database. From this library, AMPs with known anti-Gram positive activity were filtered, and 100 select AMPs were evaluated for their ability to interact with the sortase C protein using in-silico molecular docking. Based on interacting residues and docking scores, we built a preference scale to categorize candidate AMPs in order of priority for future in vitro and in vivo biofilm studies. The considerations and challenges of our approach, and the resources developed, which includes a search-enabled repository of predicted AMP structures and protein-peptide interaction models relevant to biofilm studies (B-AMP), can be leveraged for similar investigations across other biofilm targets and biofilm-forming pathogens.

scholarly journals Multidrug resistant bacteria isolated from septic arthritis in horses

2017 ◽  
Vol 37 (4) ◽  
pp. 325-330 ◽  
Author(s):  
Rodrigo G. Motta ◽  
Lorrayne S.A. Martins ◽  
Igor G. Motta ◽  
Simony T. Guerra ◽  
Carolina L. de Paula ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Septic Arthritis ◽  
Multidrug Resistant ◽  
Disk Diffusion ◽  
Nocardia Asteroides ◽  
Resistant Bacteria ◽  
In Vitro Susceptibility ◽  
Disk Diffusion Test ◽  
Streptococcus Equi

ABSTRACT: Septic arthritis is a debilitating joint infectious disease of equines that requires early diagnosis and immediate therapeutic intervention to prevent degenerative effects on the articular cartilage, as well as loss of athletic ability and work performance of the animals. Few studies have investigated the etiological complexity of this disease, as well as multidrug resistance of isolates. In this study, 60 horses with arthritis had synovial fluid samples aseptically collected, and tested by microbiological culture and in vitro susceptibility test (disk diffusion) using nine antimicrobials belonging to six different pharmacological groups. Bacteria were isolated in 45 (75.0%) samples, as follows: Streptococcus equi subsp. equi (11=18.3%), Escherichia coli (9=15.0%), Staphylococcus aureus (6=10.0%), Streptococcus equi subsp. zooepidemicus (5=8.3%), Staphylococcus intermedius (2=3.3%), Proteus vulgaris (2=3.3%), Trueperella pyogenes (2=3.3%), Pseudomonas aeruginosa (2=3.3%), Klebsiella pneumoniae (1=1.7%), Rhodococcus equi (1=1.7%), Staphylococcus epidermidis (1=1.7%), Klebsiella oxytoca (1=1.7%), Nocardia asteroides (1=1.7%), and Enterobacter cloacae (1=1.7%). Ceftiofur was the most effective drug (>70% efficacy) against the pathogens in the disk diffusion test. In contrast, high resistance rate (>70% resistance) was observed to penicillin (42.2%), enrofloxacin (33.3%), and amikacin (31.2%). Eleven (24.4%) isolates were resistant to three or more different pharmacological groups and were considered multidrug resistant strains. The present study emphasizes the etiological complexity of equine septic arthritis, and highlights the need to institute treatment based on the in vitro susceptibility pattern, due to the multidrug resistance of isolates. According to the available literature, this is the first report in Brazil on the investigation of the etiology. of the septic arthritis in a great number of horses associated with multidrug resistance of the isolates.

scholarly journals Multidrug Resistance (MDR) and Collateral Sensitivity in Bacteria, with Special Attention to Genetic and Evolutionary Aspects and to the Perspectives of Antimicrobial Peptides—A Review

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 522
Author(s):  
András Fodor ◽  
Birhan Addisie Abate ◽  
Péter Deák ◽  
László Fodor ◽  
Ervin Gyenge ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Antimicrobial Peptides ◽  
Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Mobility Patterns ◽  
Collateral Sensitivity ◽  
Resistance Evolution ◽  
Antimicrobial Peptide Resistance

Antibiotic poly-resistance (multidrug-, extreme-, and pan-drug resistance) is controlled by adaptive evolution. Darwinian and Lamarckian interpretations of resistance evolution are discussed. Arguments for, and against, pessimistic forecasts on a fatal “post-antibiotic era” are evaluated. In commensal niches, the appearance of a new antibiotic resistance often reduces fitness, but compensatory mutations may counteract this tendency. The appearance of new antibiotic resistance is frequently accompanied by a collateral sensitivity to other resistances. Organisms with an expanding open pan-genome, such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, can withstand an increased number of resistances by exploiting their evolutionary plasticity and disseminating clonally or poly-clonally. Multidrug-resistant pathogen clones can become predominant under antibiotic stress conditions but, under the influence of negative frequency-dependent selection, are prevented from rising to dominance in a population in a commensal niche. Antimicrobial peptides have a great potential to combat multidrug resistance, since antibiotic-resistant bacteria have shown a high frequency of collateral sensitivity to antimicrobial peptides. In addition, the mobility patterns of antibiotic resistance, and antimicrobial peptide resistance, genes are completely different. The integron trade in commensal niches is fortunately limited by the species-specificity of resistance genes. Hence, we theorize that the suggested post-antibiotic era has not yet come, and indeed might never come.

scholarly journals Curbing gastrointestinal infections by defensin fragment modifications without harming commensal microbiota

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Louis Koeninger ◽  
Lisa Osbelt ◽  
Anne Berscheid ◽  
Judith Wendler ◽  
Jürgen Berger ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Prolonged Exposure ◽  
Membrane Integrity ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gastrointestinal Infections ◽  
Novel Approach ◽  
Added Benefit ◽  
Eskape Pathogens

AbstractThe occurrence and spread of multidrug-resistant pathogens, especially bacteria from the ESKAPE panel, increases the risk to succumb to untreatable infections. We developed a novel antimicrobial peptide, Pam-3, with antibacterial and antibiofilm properties to counter this threat. The peptide is based on an eight-amino acid carboxyl-terminal fragment of human β-defensin 1. Pam-3 exhibited prominent antimicrobial activity against multidrug-resistant ESKAPE pathogens and additionally eradicated already established biofilms in vitro, primarily by disrupting membrane integrity of its target cell. Importantly, prolonged exposure did not result in drug-resistance to Pam-3. In mouse models, Pam-3 selectively reduced acute intestinal Salmonella and established Citrobacter infections, without compromising the core microbiota, hence displaying an added benefit to traditional broad-spectrum antibiotics. In conclusion, our data support the development of defensin-derived antimicrobial agents as a novel approach to fight multidrug-resistant bacteria, where Pam-3 appears as a particularly promising microbiota-preserving candidate.

scholarly journals Novel Antimicrobial Peptides Formulated in Chitosan Matrices are Effective Against Biofilms of Multidrug-Resistant Wound Pathogens

2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 637-643
Author(s):  
Jennifer A Neff ◽  
Danir F Bayramov ◽  
Esha A Patel ◽  
Jing Miao
Keyword(s):  
Amino Acids ◽  
Antimicrobial Peptides ◽  
Ex Vivo ◽  
Multidrug Resistant ◽  
Primary Objective ◽  
Resistant Bacteria ◽  
Chitosan Matrix ◽  
Drug Resistant Bacteria ◽  
Effective Delivery

ABSTRACT Introduction Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria. A secondary objective was to determine whether replacing the levorotatory (L) form amino acids in ASP-2 with dextrorotatory (D) form amino acids would impact peptide activity. Materials and Methods Chitosan gels loaded with antimicrobial peptides were evaluated for peptide release over 7 days and tested for efficacy against biofilms grown both in vitro on polymer mesh and ex vivo on porcine skin. Results When delivered via chitosan, 70% to 80% of peptides were released over 7 days. Gels eradicated biofilms of gram-positive and gram-negative, drug-resistant bacteria in vitro and ex vivo. Under the conditions tested, no meaningful differences in peptide activity between the L and D forms of ASP-2 were detected. Conclusions Chitosan serves as an effective delivery platform for ASP-1 and ASP-2 to treat biofilm-embedded bacteria and warrants further development as a topical treatment.

scholarly journals The prevalence and identification of multidrug-resistant bacteria in adjacent ecological systems in the Hocking Hills region of Appalachia

Fine Focus ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. 54-75
Author(s):  
Orion D. Brock ◽  
Jennifer R. Larson
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Clinical Settings ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Ecological Zones ◽  
Healthcare Settings ◽  
16S Gene

Multidrug resistance in clinical settings is a major threat to human health, but very little is known regarding the prevalence of multidrug-resistant organisms in the natural environment. Studying antibiotic resistance in the environment is important for understanding the transfer of resistance between environmental microorganisms and those found in healthcare settings. In this study, soil samples from seven adjacent ecological zones were evaluated to determine if there were differences in the amount and types of antibiotic-resistant bacteria present. We hypothesized that we would find antibiotic-resistant bacteria in all ecological zones studied and that these bacteria would be unique to their specific niche. Several resistant organisms from each site were also tested for multidrug resistance and subsequently identified through DNA sequencing of the 16S gene. Antibiotic resistance was discovered in all sites at varying percentages. Some forms of bacteria were present at all sites, but there were differences in types of resistant bacteria found between sites. Six different genera of bacteria were identified, and multidrug resistance was found in all the isolates studied. Our findings indicate that multidrug resistance is prevalent in many different types of environments, including those that have never been directly used for agricultural or urban development.

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