Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections.
Microbiome-derived antimicrobial peptides offer therapeutic solutions for the treatment of Pseudomonas aeruginosa infections.
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DOI：
10.1038/s41522-022-00332-w
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发表时间：
2022-08-29
影响因子：
9.2
通讯作者：
Huws, Sharon A.
中科院分区：
文献类型：
--
作者：
Mulkern, Adam J.;Oyama, Linda B.;Cookson, Alan R.;Creevey, Christopher J.;Wilkinson, Toby J.;Olleik, Hamza;Maresca, Marc;da Silva, Giarla C.;Fontes, Patricia P.;Bazzolli, Denise M. S.;Mantovani, Hilario C.;Damaris, Bamu F.;Mur, Luis A. J.;Huws, Sharon A.
由于微生物组的复杂性和多样性，微生物组（特别是瘤胃微生物组）在生物技术开发中很普遍。在这项研究中，来自瘤胃微生物组（Lynronne 1，2，3和P15）的抗菌肽（AMP）被评估其对七种铜绿假单胞菌临床菌株的治疗潜力。所有AMP对所有菌株均表现出抗微生物活性，最小抑制浓度（MIC）范围为4-512 µg/mL。所有AMP在3× MIC值下对菌株PAO 1和LES 431的时间杀灭动力学显示在10 min至4 h内完全杀灭，尽管P15 s对PAO 1没有杀菌作用。所有AMP均显著抑制菌株PAO 1和LES 431的生物膜形成，并且诱导抗性测定显示对这些菌株的活性没有降低。AMP对人肺细胞的细胞毒性也很小。在作用机制方面，AMP显示出对PAO 1和LES 431细菌膜脂质的亲和力，有效地透化铜绿假单胞菌膜。转录组和代谢组分析显示，细胞膜上的催化活性增加，促进脂肪酸的β-氧化。最后，用Galleria mellonella感染模型进行的测试显示Lynronne 1和2在体内是有效的，分别在32 mg/kg和128 mg/kg处理后具有100%的存活率。这项研究说明了微生物组来源的AMP对铜绿假单胞菌感染的治疗潜力。
Microbiomes are rife for biotechnological exploitation, particularly the rumen microbiome, due to their complexicity and diversity. In this study, antimicrobial peptides (AMPs) from the rumen microbiome (Lynronne 1, 2, 3 and P15s) were assessed for their therapeutic potential against seven clinical strains of Pseudomonas aeruginosa. All AMPs exhibited antimicrobial activity against all strains, with minimum inhibitory concentrations (MICs) ranging from 4–512 µg/mL. Time-kill kinetics of all AMPs at 3× MIC values against strains PAO1 and LES431 showed complete kill within 10 min to 4 h, although P15s was not bactericidal against PAO1. All AMPs significantly inhibited biofilm formation by strains PAO1 and LES431, and induction of resistance assays showed no decrease in activity against these strains. AMP cytotoxicity against human lung cells was also minimal. In terms of mechanism of action, the AMPs showed affinity towards PAO1 and LES431 bacterial membrane lipids, efficiently permeabilising the P. aeruginosa membrane. Transcriptome and metabolome analysis revealed increased catalytic activity at the cell membrane and promotion of β-oxidation of fatty acids. Finally, tests performed with the Galleria mellonella infection model showed that Lynronne 1 and 2 were efficacious in vivo, with a 100% survival rate following treatment at 32 mg/kg and 128 mg/kg, respectively. This study illustrates the therapeutic potential of microbiome-derived AMPs against P. aeruginosa infections.
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影响因子：
5.2
作者：
Huws SA;Creevey CJ;Oyama LB;Mizrahi I;Denman SE;Popova M;Muñoz-Tamayo R;Forano E;Waters SM;Hess M;Tapio I;Smidt H;Krizsan SJ;Yáñez-Ruiz DR;Belanche A;Guan L;Gruninger RJ;McAllister TA;Newbold CJ;Roehe R;Dewhurst RJ;Snelling TJ;Watson M;Suen G;Hart EH;Kingston-Smith AH;Scollan ND;do Prado RM;Pilau EJ;Mantovani HC;Attwood GT;Edwards JE;McEwan NR;Morrisson S;Mayorga OL;Elliott C;Morgavi DP
通讯作者：
Morgavi DP
影响因子：
5.2
作者：
Arai H
通讯作者：
Arai H
D-氨基酸取代增强抗菌肽polybia-CP的稳定性
影响因子：
3.7
作者：
Jia, Fengjing;Wang, Jiayi;Wang, Rui
通讯作者：
Wang, Rui
影响因子：
--
作者：
Jorgensen, J. H.
通讯作者：
Jorgensen, J. H.
影响因子：
4.8
作者：
Mahfoud, R;Garmy, N;Fantini, J
通讯作者：
Fantini, J