scholarly journals Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260003
Author(s):  
Phantitra Sudadech ◽  
Sittiruk Roytrakul ◽  
Orawee Kaewprasert ◽  
Auttawit Sirichoat ◽  
Ploenchan Chetchotisakd ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Mycobacterium Abscessus ◽  
Adjunctive Treatment ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Clarithromycin Resistance ◽  
Drug Resistant Bacteria ◽  
Treatment Failure Rate ◽  
High Treatment

Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200–400 μg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 μg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 μg/ml of four potential AMPs, S61, S62, S63 and KLK1 after 3-days-incubation. At the MICs level, S63 showed the lowest toxicity with 1.50% hemolysis and 100% PBMC viability whereas KLK1 showed the highest hemolysis (10.21%) and lowest PBMC viability (93.52%). S61, S62 and S63 were further tested with clarithromycin-AMP interaction assays and found that 5/10 (50%) of selected isolates exhibited a synergistic interaction with 0.02–0.41 FICI values. This present study demonstrated the potential application of novel AMPs as an adjunctive treatment with clarithromycin against drug resistant Mab infection.

scholarly journals Agreement Assessment of Tigecycline Susceptibilities Determined by the Disk Diffusion and Broth Microdilution Methods among Commonly Encountered Resistant Bacterial Isolates: Results from the TigecyclineIn VitroSurveillance in Taiwan (TIST) Study, 2008 to 2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1414-1417 ◽  
Author(s):  
Jien-Wei Liu ◽  
Wen-Chien Ko ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Total Error ◽  
Error Rates ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor thein vitroactivity of tigecycline against commonly encountered drug-resistant bacteria. This study compared thein vitroactivity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistantStaphylococcus aureus(MRSA;n= 759), vancomycin-resistantEnterococcus faecium(VRE;n= 191), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 602), ESBL-producingKlebsiella pneumoniae(n= 736), andAcinetobacter baumannii(n= 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC90values of tigecycline against MRSA, VRE, ESBL-producingE. coli, ESBL-producingK. pneumoniae, andA. baumanniiwere 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producingK. pneumoniaeand 33.8% forA. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) forA. baumanniiisolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producingE. coli. For routine susceptibility testing of ESBL-producingK. pneumoniaeandA. baumanniiagainst tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

scholarly journals Nanoparticles Enable Efficient Delivery of Antimicrobial Peptides for the Treatment of Deep Infections

2021 ◽  
Author(s):  
Yingxue Deng ◽  
Rui Huang ◽  
Songyin Huang ◽  
Menghua Xiong
Keyword(s):  
Antimicrobial Peptides ◽  
Broad Spectrum ◽  
Antimicrobial Properties ◽  
Therapeutic Index ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Efficient Delivery ◽  
Delivery Vehicles

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.

scholarly journals Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria

2020 ◽  
Vol 21 (16) ◽  
pp. 5773 ◽  
Author(s):  
Surajit Bhattacharjya ◽  
Suzana K. Straus
Keyword(s):  
Antimicrobial Peptides ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibiotic Development ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Drying Up ◽  
Further Development ◽  
Lps Binding

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.

An active domain HF-18 derived from hagfish intestinal peptide effectively inhibited drug-resistant bacteria in vitro/vivo

2020 ◽  
Vol 172 ◽  
pp. 113746
Author(s):  
Meiling Jiang ◽  
Xiaoqian Yang ◽  
Haomin Wu ◽  
Ya Huang ◽  
Jie Dou ◽  
...  
Keyword(s):  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

scholarly journals LAMP2: a major update of the database linking antimicrobial peptides

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Guizi Ye ◽  
Hongyu Wu ◽  
Jinjiang Huang ◽  
Wei Wang ◽  
Kuikui Ge ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Primary Structure ◽  
Scientific Community ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Current Version ◽  
Functional Activities ◽  
Drug Resistant Bacteria ◽  
Functional Classes ◽  
And Function

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.

scholarly journals Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the TigecyclineIn VitroSurveillance in Taiwan Study, 2006 to 2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1452-1457 ◽  
Author(s):  
Yen-Hsu Chen ◽  
Po-Liang Lu ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  
Keyword(s):  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria ◽  
Vancomycin Resistant ◽  
Susceptibility Rate ◽  
Important Drug

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistantStaphylococcus aureus(MRSA) (n= 1,834), penicillin-resistantStreptococcus pneumoniae(PRSP) (n= 423), vancomycin-resistant enterococci (VRE) (n= 219), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 1,141), ESBL-producingKlebsiella pneumoniae(n= 1,330),Acinetobacter baumannii(n= 1,645), andStenotrophomonas maltophilia(n= 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC90, 0.03 μg/ml), and only one MRSA isolate (MIC90, 0.5 μg/ml) and three VRE isolates (MIC90, 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producingE. coli(MIC90, 0.5 μg/ml) and 96.32% for ESBL-producingK. pneumoniae(MIC90, 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate forA. baumannii(MIC90, 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptibleA. baumanniiisolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptibleA. baumanniiisolates. In Taiwan, tigecycline continues to have excellentin vitroactivity against several major clinically important drug-resistant bacteria, with the exception ofA. baumannii.

scholarly journals Developing an antibiotic effective against multi-drug resistant bacteria.

2014 ◽  
Vol 70 (a1) ◽  
pp. C714-C714
Author(s):  
Calvin Steussy ◽  
Cynthia Stauffacher ◽  
Mark Lipton ◽  
Mohamed Seleem
Keyword(s):  
Pathogenic Bacteria ◽  
Modern Medicine ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Lead Compound ◽  
Drug Resistant Bacteria ◽  
Coa Reductase

The emergence of multi-drug resistant pathogenic bacteria is one of the great challenges to modern medicine. The gram positive cocci Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus faecalis (VRE) are two particularly virulent examples. In vivo studies have shown that the eukaryotic like 'mevalonate' isoprenoid pathway used by these pathogenic cocci is essential to their growth and virulence [1]. Our structures of HMG-CoA reductase (HMGR) from P. mevalonii demonstrated that the bacterial enzymes are structurally distinct from the human enzymes allowing for specific antibacterial activity [2]. High throughput in vitro screening against bacterial HMGR at the Southern Research Center, Birmingham, AL uncovered a lead compound with an IC50 of 80 µM with a competitive mode of action. Our x-ray crystal structures of HMGR from E. faecalis complexed with the lead compound and its variations have informed the synthesis of new inhibitors that have improved the IC50 to 5 µM [3]. Studies of this compound show it to be active against both MRSA and VRE in culture, effective against these bacteria in biofilms, and efficacious in a model system of eukaryotic infection. Structures and kinetics of these compounds will be presented and future directions discussed.

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