A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria

Current research in the field of antimicrobials is focused on the development of novel antibiotics and antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host Defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they share unique characteristics suitable for antimicrobial activity including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that was identified through molecular cloning from the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against different strains of Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displaying significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was designed from the naturally occurring scorpion venom host defense peptide. The design strategy depended on modifying the amino acid sequence of the parent peptide in order to increase its net positive charge, percentage helicity and optimize other physico-chemical parameters involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 displayed potent and selective in vitro antimicrobial activities against a wide range of MDR Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics displayed a synergistic mode of action which resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. These effective concentrations were associated with negligible toxicities on mammalian cells. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDR and biofilm forming bacteria.

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DNA Binding Ligands with Excellent Antibiotic Potency Against Drug-Resistant Gram-Positive Bacteria.

ChemInform ◽

10.1002/chin.200306197 ◽

2003 ◽

Vol 34 (6) ◽

Author(s):

Roland W. Buerli ◽

Yigong Ge ◽

Sarah White ◽

Eldon E. Baird ◽

Sofia M. Touami ◽

...

Keyword(s):

Dna Binding ◽

Drug Resistant ◽

Gram Positive ◽

Gram Positive Bacteria

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Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2009.08.026 ◽

2009 ◽

Vol 17 (19) ◽

pp. 6879-6889 ◽

Cited By ~ 11

Author(s):

Rie Miyauchi ◽

Katsuhiro Kawakami ◽

Masao Ito ◽

Norikazu Matsuhashi ◽

Hitoshi Ohki ◽

...

Keyword(s):

Antibacterial Activity ◽

Drug Resistant ◽

Gram Positive ◽

Design Synthesis ◽

Gram Positive Bacteria

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In Vitro Activity of Eravacycline against Gram-Positive Bacteria Isolated in Clinical Laboratories Worldwide from 2013 to 2017

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01715-19 ◽

2019 ◽

Vol 64 (3) ◽

Cited By ~ 1

Author(s):

Ian Morrissey ◽

Stephen Hawser ◽

Sibylle H. Lob ◽

James A. Karlowsky ◽

Matteo Bassetti ◽

...

Keyword(s):

Antimicrobial Agents ◽

Clinical Isolates ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria ◽

Microdilution Method ◽

Clinical Laboratories ◽

Broth Microdilution Method ◽

Doubling Dilution

ABSTRACT Eravacycline is a novel, fully synthetic fluorocycline antibiotic being developed for the treatment of serious infections, including those caused by resistant Gram-positive pathogens. Here, we evaluated the in vitro activities of eravacycline and comparator antimicrobial agents against a recent global collection of frequently encountered clinical isolates of Gram-positive bacteria. The CLSI broth microdilution method was used to determine in vitro MIC data for isolates of Enterococcus spp. (n = 2,807), Staphylococcus spp. (n = 4,331), and Streptococcus spp. (n = 3,373) isolated primarily from respiratory, intra-abdominal, urinary, and skin specimens by clinical laboratories in 37 countries on three continents from 2013 to 2017. Susceptibilities were interpreted using both CLSI and EUCAST breakpoints. There were no substantive differences (a >1-doubling-dilution increase or decrease) in eravacycline MIC90 values for different species/organism groups over time or by region. Eravacycline showed MIC50 and MIC90 results of 0.06 and 0.12 μg/ml, respectively, when tested against Staphylococcus aureus, regardless of methicillin susceptibility. The MIC90 values of eravacycline for Staphylococcus epidermidis and Staphylococcus haemolyticus were equal (0.5 μg/ml). The eravacycline MIC90s for Enterococcus faecalis and Enterococcus faecium were 0.06 μg/ml and were within 1 doubling dilution regardless of the vancomycin susceptibility profile. Eravacycline exhibited MIC90 results of ≤0.06 μg/ml when tested against Streptococcus pneumoniae and beta-hemolytic and viridans group streptococcal isolates. In this surveillance study, eravacycline demonstrated potent in vitro activity against frequently isolated clinical isolates of Gram-positive bacteria (Enterococcus, Staphylococcus, and Streptococcus spp.), including isolates collected over a 5-year period (2013 to 2017), underscoring its potential benefit in the treatment of infections caused by common Gram-positive pathogens.

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Therapeutic Potential of a Scorpion Venom-Derived Antimicrobial Peptide and Its Homologs Against Antibiotic-Resistant Gram-Positive Bacteria

Frontiers in Microbiology ◽

10.3389/fmicb.2018.01159 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 8

Author(s):

Gaomin Liu ◽

Fan Yang ◽

Fangfang Li ◽

Zhongjie Li ◽

Yange Lang ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Therapeutic Potential ◽

Scorpion Venom ◽

Gram Positive ◽

Antibiotic Resistant ◽

Gram Positive Bacteria

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Comparative Surveillance Study of Telavancin Activity against Recently Collected Gram-Positive Clinical Isolates from across the United States

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01641-07 ◽

2008 ◽

Vol 52 (7) ◽

pp. 2383-2388 ◽

Cited By ~ 68

Author(s):

Deborah C. Draghi ◽

Bret M. Benton ◽

Kevin M. Krause ◽

Clyde Thornsberry ◽

Chris Pillar ◽

...

Keyword(s):

United States ◽

The United States ◽

Clinical Isolates ◽

Surveillance Study ◽

Coagulase Negative Staphylococci ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Serious Infections ◽

Wide Range ◽

Vancomycin Resistant

ABSTRACT Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 μg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC90s, 0.03 to 0.12 μg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC90, 1 μg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC90, 2 μg/ml) but less active against VanA strains (MIC90, 8 to 16 μg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 μg/ml to 1.0 μg/ml and 1.0 μg/ml to 4.0 μg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.

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DNA binding ligands targeting drug-resistant Gram-positive bacteria. Part 1: Internal benzimidazole derivatives

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2003.12.042 ◽

2004 ◽

Vol 14 (5) ◽

pp. 1253-1257 ◽

Cited By ~ 87

Author(s):

Roland W. Bürli ◽

Dustin McMinn ◽

Jacob A. Kaizerman ◽

Wenhao Hu ◽

Yigong Ge ◽

...

Keyword(s):

Dna Binding ◽

Benzimidazole Derivatives ◽

Drug Resistant ◽

Gram Positive ◽

Gram Positive Bacteria

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In vitro activity of quinupristin/dalfopristin against clinical isolates of common gram-positive bacteria in Taiwan

Diagnostic Microbiology and Infectious Disease ◽

10.1016/s0732-8893(98)00147-3 ◽

1999 ◽

Vol 33 (4) ◽

pp. 299-303 ◽

Cited By ~ 3

Author(s):

Shan-Chwen Chang ◽

Chi-Tai Fang ◽

Po-Ren Hsueh ◽

Kwen-Tay Luh ◽

Wei-Chuan Hsieh

Keyword(s):

Vitro Activity ◽

Clinical Isolates ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Positive Bacteria

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An alpha/beta chimeric peptide molecular brush for eradicating MRSA biofilms and persister cells to mitigate antimicrobial resistance

Biomaterials Science ◽

10.1039/d0bm01211d ◽

2020 ◽

Vol 8 (24) ◽

pp. 6883-6889 ◽

Cited By ~ 1

Author(s):

Ximian Xiao ◽

Si Zhang ◽

Sheng Chen ◽

Yuxin Qian ◽

Jiayang Xie ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Drug Resistant ◽

Excellent Performance ◽

Persister Cells ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Chimeric Peptide ◽

Alpha Beta ◽

Chimeric Polypeptide

An α/β chimeric polypeptide molecular brush shows excellent performance in eradicating established biofilms, persister cells, and clinically isolated multi-drug resistant Gram-positive bacteria.

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