Cec4-Derived Peptide Inhibits Planktonic and Biofilm-Associated Methicillin Resistant Staphylococcus epidermidis

Mao, Chengju; Wang, Yue; Yang, Yifan; Li, Lü; Yuan, Kun; Cao, Huijun; Qiu, Zhilang; Guo, Guo; Wu, Jian-Wei; Peng, Jian

doi:10.1128/spectrum.02409-22

Cited by 7 publications

(4 citation statements)

References 65 publications

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“…Contextually, more than 3000 AMPs have been reported to elicit activity against bacteria in their planktonic as well as sessile lifecycle so far [24,25]. In contrast to the single target of classic antibiotics, AMPs can exert their antibacterial activity impairing the cell membrane structure, permeability, and fluidity, and/or interfering with nucleic acids and protein synthesis pathways, triggering stress and ROS accumulation [26,27]. Thanks to their multihit, broad-spectrum action, AMPs may also provide a potential new therapeutic solution against MDR strains, supporting and enhancing the effectiveness of commercially available antibiotics [28].…”

Section: Discussionmentioning

confidence: 99%

Oreoch-1: A Peptide from Oreochromis niloticus as a Potential Tool against Staphylococci

Palma,

Chianese,

Panico

et al. 2023

Pathogens

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Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis, are important human pathogens associated with potentially life-threatening infections. Their great biofilm-producing ability and the development of resistance mechanisms often account for therapeutic failure. Hence, the scientific community has devoted intensive efforts to the development of antimicrobial compounds active against both planktonic and sessile bacterial populations. Contextually, antimicrobial peptides (AMPs) are natural peptides produced by the innate immunity of every organism, representing a potential new therapeutic solution against human microbial pathogens. Our work focused on the in vitro activity of Oreoch-1, an AMP from the gills of Nile tilapia (Oreochromis niloticus), against standard and clinical S. aureus and S. epidermidis strains. Firstly, the cytotoxicity profile of Oreoch-1 was determined in human colon carcinoma cells. Secondly, its antibacterial spectrum was explored against staphylococcal strains to set up the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Our results highlighted an antibacterial activity in the range 6.25–25 μM, with a general bacteriostatic effect. Therefore, the biofilm-inhibitory property was assessed against S. aureus ATCC 25923 and S. epidermidis ATCC 35984, indicating a significant reduction in S. aureus biomass at sub-MIC concentrations. Overall, our study indicates Oreoch-1 as a promising new therapeutic weapon against staphylococcal infections.

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Section: Discussionmentioning

confidence: 99%

Oreoch-1: A Peptide from Oreochromis niloticus as a Potential Tool against Staphylococci

Palma,

Chianese,

Panico

et al. 2023

Pathogens

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“…The RNA extraction was performed according to the instruction manual of the RNA extraction kit (Axygen, Sigma-Aldrich, St. Louis, MO, USA). 28 Total RNA was detected by 1% agarose gel electrophoresis, and the concentration and quality of total RNA were determined by Nanodrop Spectrophotometer (ND-200, Thermo Scientific, Waltham, MA, USA). The remaining RNA was stored at −20 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The bacterial suspension exposed to 0.5 × MIC was resuspended and grown to the logarithmic phase to determine the MIC with corresponding drugs. 28 The above steps were repeated to 30 generations, and then the 30th-generation strain was subcultured without Cec4 for 10 generations. C-7 is the Cec4-resistant isolate at seventh passage from A. baumannii ATCC19606 cultured in the presence of Cec4 sub-inhibitory concentrations.…”

Section: Methodsmentioning

confidence: 99%

Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo

Peng¹,

Wang²,

Wu³

et al. 2023

DDDT

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Introduction Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive. Methods The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed. Results Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii . In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans , even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection. Conclusion In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections.

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“…Finally, the glass slides were dried and coated with gold for imaging ( 55 ). For TEM, glutaraldehyde samples were cryoimmobilized and subjected to TEM imaging ( 58 , 59 ).…”

Section: Methodsmentioning

confidence: 99%

Rational Design of Stapled Antimicrobial Peptides to Enhance Stability and In Vivo Potency against Polymicrobial Sepsis

et al. 2023

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Cec4-Derived Peptide Inhibits Planktonic and Biofilm-Associated Methicillin Resistant Staphylococcus epidermidis

Abstract: S. epidermidis is one of the most important pathogens of graft-related infection and hospital-acquired infection. The growing problem of antibiotic resistance, as well as the emergence of bacterial pathogenicity, highlights the need for antimicrobials with new modes of action.

Cited by 7 publications

References 65 publications

Oreoch-1: A Peptide from Oreochromis niloticus as a Potential Tool against Staphylococci

Oreoch-1: A Peptide from Oreochromis niloticus as a Potential Tool against Staphylococci

Antimicrobial Peptide Cec4 Eradicates Multidrug-Resistant Acinetobacter baumannii in vitro and in vivo

Rational Design of Stapled Antimicrobial Peptides to Enhance Stability and In Vivo Potency against Polymicrobial Sepsis

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