Dataset Information

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.

ABSTRACT: Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced by four-helix bacteriocins, epidermicin NI01 and aureocin A53. Using a combination of crystallography, spectroscopy, bioassays, and nanoscale imaging, we established that individual two-helix segments of epidermicin retain antibacterial activity but each of these segments adopts a particular poration mode. In the intact protein these segments act synergistically to balance out antibacterial and hemolytic activities. The study sets a precedent of multi-mode membrane disruption advancing the current understanding of structure-activity relationships in pore-forming proteins.

SUBMITTER: Hammond K

PROVIDER: S-EPMC7424198 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.

Hammond Katharine K Lewis Helen H Halliwell Samantha S Desriac Florie F Nardone Brunello B Ravi Jascindra J Hoogenboom Bart W BW Upton Mathew M Derrick Jeremy P JP Ryadnov Maxim G MG

iScience 20200730 8

Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced by four-helix bacteriocins, epidermicin NI01 and aureocin A53. Using a combination of crystallography, spectroscopy, bioassays, and nanoscale imaging, we established that individual two-helix segments of epidermicin retain antibacterial activity but each o ...[more]

PMID: 32795916

Similar Datasets

Project description:Enterobacter cloacae is a troublesome pathogen causing refractory infections of the lower respiratory tract, urethra and abdominal cavity, endocarditis, osteomyelitis, and neonatal septicemia. It is prone to developing resistance to ordinary antibiotics and has brought a serious problem to clinical treatment. An artful synergistic combination of an antibacterial natural product allicin and a newly isolated bacteriophage, named BD523, was constructed herein. This combination significantly lowered effective dosage of allicin and effectually overcame bacterial drug-resistance. We experimentally evidenced that allicin interacts with bacterial DNA in the groove region by inserting itself into the DNA double helix and, subsequently, disrupts the bacterial DNA by cleaving phosphate diester bonds of deoxynucleotides. Further, BD523 destroys the cell wall and membrane of bacteria by synthesizing lyase proteins, including holin and endolysins. Thus, the synergistic effect of the combination benefits from complementary targeting mechanisms of allicin and BD523. They cooperatively act on bacterial DNA, cell wall, and membrane to improve antibacterial efficiency and avoid drug-resistance. IMPORTANCE Bacterial drug-resistance is a serious problem afflicting pharmacologists all over the world. Many strategies have been developed and practiced to overcome it, but almost no one is satisfactory due to the continual change of bacteria. Combinations of antibiotics and bacteriophages are promising because of the cooperation of 2 bacterial killers with distinct mechanisms. The combination of allicin and an Enterobacter cloacae bacteriophage reported herein can significantly improve the effect of allicin against E. cloacae. Its synergistic effect was even superior to the combination of bacteriophage and neomycin, of which the MIC was significantly lower than allicin. It was ascribed to the complementary antibacterial and the possible resistance-proof mechanism of bacteriophage and allicin. This study provided a pragmatic way to conquer the cunning bacterium, and may offer reference for research and development of new bacterial killers.

Project description:Bacterial infections are one of the leading causes of death worldwide. In the case of topical bacterial infections such as wound infections, silver (Ag) has historically been one of the most widely used antibacterials. However, scientific publications have demonstrated the adverse effects of silver on human cells, ecotoxicity and insufficient antibacterial effect for the complete elimination of bacterial infections. The use of Ag in the form of nanoparticles (NPs, 1-100 nm) allows to control the release of antibacterial Ag ions but is still not sufficient to eliminate infection and avoid cytotoxicity. In this study, we tested the potency of differently functionalized copper oxide (CuO) NPs to enhance the antibacterial properties of Ag NPs. The antibacterial effect of the mixture of CuO NPs (CuO, CuO-NH2 and CuO-COOH NPs) with Ag NPs (uncoated and coated) was studied. CuO and Ag NP combinations were more efficient than Cu or Ag (NPs) alone against a wide range of bacteria, including antibiotic-resistant strains such as gram-negative Escherichia coli and Pseudomonas aeruginosa as well as gram-positive Staphylococcus aureus, Enterococcus faecalis and Streptococcus dysgalactiae. We showed that positively charged CuO NPs enhanced the antibacterial effect of Ag NPs up to 6 times. Notably, compared to the synergy of CuO and Ag NPs, the synergy of respective metal ions was low, suggesting that NP surface is required for the enhanced antibacterial effect. We also studied the mechanisms of synergy and showed that the production of Cu+ ions, faster dissolution of Ag+ from Ag NPs and lower binding of Ag+ by proteins of the incubation media in the presence of Cu2+ were the main mechanisms of the synergy. In summary, CuO and Ag NP combinations allowed increasing the antibacterial effect up to 6 times. Thus, using CuO and Ag NP combinations enables to retain excellent antibacterial effects due to Ag and synergy and enhances beneficial effects, since Cu is a vital microelement for human cells. Thus, we suggest using combinations of Ag and CuO NPs in antibacterial materials, such as wound care products, to increase the antibacterial effect of Ag, improve safety and prevent and cure topical bacterial infections.

Dataset Information

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.

Publications

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets