Potent antibacterial activity of MSI-1 derived from the magainin 2 peptide against drug-resistant bacteria

Ma, Lingman; Xie, Xin; Liu, Hanhan; Huang, Ya; Wu, Haixia; Jiang, Meiling; Xu, Pengfei; Ye, Xinyue; Zhou, Changlin

doi:10.7150/thno.39157

Cited by 40 publications

(42 citation statements)

References 40 publications

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“…Hemolytic activity of colistin in the presence of melatonin was evaluated based on previous reports 33 , 34 . 8% sheep blood cells were treated with colistin (16 to 128 μg/mL) and/or melatonin (0 to 1,000 μg/mL) for 1 h. Triton X-100 (0.2%) was used as a positive control.…”

Section: Methodsmentioning

confidence: 99%

Melatonin overcomes MCR-mediated colistin resistance in Gram-negative pathogens

Jia

Yang

et al. 2020

Theranostics

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Background: Emergence, prevalence and widely spread of plasmid-mediated colistin resistance in Enterobacteriaceae strongly impairs the clinical efficacy of colistin against life-threatening bacterial infections. Combinations of antibiotics and FDA-approved non-antibiotic agents represent a promising means to address the widespread emergence of antibiotic-resistant pathogens. Methods: Herein, we investigated the synergistic activity between melatonin and antibiotics against MCR (mobilized colistin resistance)-positive Gram-negative pathogens through checkerboard assay and time-killing curve. Molecular mechanisms underlying its mode of action were elucidated. Finally, we assessed the in vivo efficacy of melatonin in combination with colistin against drug-resistant Gram-negative bacteria. Results: Melatonin, which has been approved for treating sleep disturbances and circadian disorders, substantially potentiates the activity of three antibiotics, particularly colistin, against MCR-expressing pathogens without enhancing its toxicity. This is evidence that the combination of colistin with melatonin enhances bacterial outer membrane permeability, promotes oxidative damage and inhibits the effect of efflux pumps. In three animal models infected by mcr-1 -carrying E. coli , melatonin dramatically rescues colistin efficacy. Conclusion: Our findings revealed that melatonin serves as a promising colistin adjuvant against MCR-positive Gram-negative pathogens.

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Section: Methodsmentioning

confidence: 99%

Melatonin overcomes MCR-mediated colistin resistance in Gram-negative pathogens

Jia

Yang

et al. 2020

Theranostics

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“…The great stability of AMPs is a critical prerequisite for its in vivo efficacy [ 40 ]. Therefore, we assessed the residual antibacterial activity of WW307 after exposure to different temperatures and pH conditions [ 21 ]. Surprisingly, WW307 completely retained its activity after treatment under 40–121 °C or pH (2 to 12) for 1 h, indicating that WW307 possessed great thermal and pH stability ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…CD spectra of the peptides in four different solvents, including 0.01 M PBS (pH = 7.2), 50 μM LPS, 50 mM sodium dodecyl sulfate (SDS), and 50% trifluoroethanol (TFEA) [ 21 ], were measured using a J-810 spectropolarimeter (Jasco, Tokyo, Japan) at 25 °C. The wavelength recorded values were 190–300 nm, and the measurements were repeated three times.…”

Section: Methodsmentioning

confidence: 99%

“…For example, a synthetic derivative of human AMPs LL-37, termed SAAP-148, exhibited improved bactericidal activity and plasma stability in killing MDR pathogens, including biofilm-producing bacteria and persister cells [ 20 ]. In addition, the truncation of MSI-78 at the N -terminal resulted in a 14-amino-acids AMPs named MSI-1 [ 21 ], which displayed superior activity and lower toxicity than its parent AMPs. Recently, two amphipathic peptide antibiotics termed horine and verine with systemic efficiency in mice infection models were identified [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens

et al. 2021

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The emergence and prevalence of multidrug-resistant (MDR) bacteria have posed a serious threat to public health. Of particular concern are methicillin-resistant Staphylococcus aureus (MRSA) and blaNDM, mcr-1 and tet(X)-positive Gram-negative pathogens. The fact that few new antibiotics have been approved in recent years exacerbates this global crisis, thus, new alternatives are urgently needed. Antimicrobial peptides (AMPs) originated from host defense peptides with a wide range of sources and multiple functions, are less prone to achieve resistance. All these characteristics laid the foundation for AMPs to become potential antibiotic candidates. In this study, we revealed that peptide WW307 displayed potent antibacterial and bactericidal activity against MDR bacteria, including MRSA and Gram-negative bacteria carrying blaNDM-5, mcr-1 or tet(X4). In addition, WW307 exhibited great biofilm inhibition and eradication activity. Safety and stability experiments showed that WW307 had a strong resistance against various physiological conditions and displayed relatively low toxicity. Mechanistic experiments showed that WW307 resulted in membrane damage by selectively targeting bacterial membrane-specific components, including lipopolysaccharide (LPS), phosphatidylglycerol (PG), and cardiolipin (CL). Moreover, WW307 dissipated membrane potential and triggered the production of reactive oxygen species (ROS). Collectively, these results demonstrated that WW307 represents a promising candidate for combating MDR pathogens.

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“…Cationic AMP have received intense interest because of their multiple models of action for new antimicrobial therapeutics [9]. Growing evidence supports that AMP kill bacteria or fungi partly due to their direct membrane disruption activity [8,47], whose selectivity depends on the unique membrane composition, particularly the membrane charge. The cationic charge of the peptides leads to their several-fold accumulation next to negatively charged surfaces of gram-negative bacteria or fungi, which present very different outer surfaces to attacking AMP [9].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial and antibiofilm activity of the EeCentrocin 1 derived peptide EC1-17KV via membrane disruption

Sun

et al. 2020

eBioMedicine

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Background: The antibiotic resistance and biofilm formation of pathogenic microbes exacerbate the difficulties of anti-infection therapy in the clinic. The structural modification of antimicrobial peptides (AMP) is an effective strategy to develop novel anti-infective agents. Method: Seventeen amino acids (AA) in the longer chain of EeCentrocin 1 (from the edible sea-urchin Echinus esculentus) were truncated and underwent further modification. To produce lead peptides with low toxicity and high efficacy, the antimicrobial activity or cytotoxicity of peptides was evaluated against various multidrug-resistant bacteria/fungi or mammalian cells in vivo/ in vitro. In addition, the stability and modes of action of the lead peptide were investigated. Findings: EC1-17KV displayed potent activity and an expanded antimicrobial spectrum, especially against drug-resistant gram-negative bacteria and fungi, attributable to its enhanced amphiphilicity and net charge. In addition, it exhibits bactericidal/fungicidal activity and effectively increased the animal survival rate and mitigated the histopathological damage induced by multidrug-resistant P. aeruginosa or C. albicans in infected mice or G. mellonella. Moreover, EC1-17KV had a poor ability to induce resistance in bacteria and fungi and exhibited desirable high-salt/high-temperature tolerance properties. In bacteria, EC1-17KV promoted divalent cation release to damage bacterial membrane integrity. In fungi, it changed C. albicans membrane fluidity to increase membrane permeabilization or reduced hyphal formation to suppress biofilm formation. Interpretation: EC1-17KV is a promising lead peptide for the development of antimicrobial agents against antibiotic resistant bacteria and fungi.

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Potent antibacterial activity of MSI-1 derived from the magainin 2 peptide against drug-resistant bacteria

Cited by 40 publications

References 40 publications

Melatonin overcomes MCR-mediated colistin resistance in Gram-negative pathogens

Melatonin overcomes MCR-mediated colistin resistance in Gram-negative pathogens

Amphipathic Peptide Antibiotics with Potent Activity against Multidrug-Resistant Pathogens

Antimicrobial and antibiofilm activity of the EeCentrocin 1 derived peptide EC1-17KV via membrane disruption

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