A D-enantiomer of the antimicrobial peptide GL13K evades antimicrobial resistance in the Gram positive bacteria Enterococcus faecalis and Streptococcus gordonii.
A D-enantiomer of the antimicrobial peptide GL13K evades antimicrobial resistance in the Gram positive bacteria Enterococcus faecalis and Streptococcus gordonii.
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DOI：
10.1371/journal.pone.0194900
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Gorr SU
中科院分区：
文献类型：
--
作者：
Hirt H;Hall JW;Larson E;Gorr SU
抗微生物肽代表了传统抗生素的替代品，其可能通过直接攻击细菌细胞膜而对细菌耐药性机制不太敏感。然而，细菌具有多种防御机制，可以阻止阳离子抗菌肽到达细胞膜。抗微生物肽GL 13 K的L-和D-对映体针对革兰氏阳性细菌粪肠球菌和戈登链球菌进行了测试，以了解细菌蛋白酶和细胞壁修饰在细菌抗性中的作用。GL 13 K来源于人唾液蛋白BPIFA 2。通过肉汤稀释和用于确定细菌耐药性的系列测定来确定最小抑菌浓度。在生物测定中利用铜绿假单胞菌的发光菌株测定肽降解以检测肽活性。自溶和D-丙氨酰化缺陷株E. faecalis和S. Gordonii在自溶测定和肽活性测定中进行测试。E. faecalis蛋白酶使L-GL 13 K失活，但不使D-GL 13 K失活，而自溶不影响肽活性。事实上，D-对映体似乎在自溶开始之前杀死细菌。D-丙氨酰化突变体被L-GL 13 K杀死，而这种修饰不影响D-GL 13 K的杀死。突变体恢复了对L-GL 13 K的抗性，而细菌在用肽重复处理后没有获得对D-GL 13 K的抗性。D-丙氨酰化影响细菌细胞的疏水性，但疏水性本身并不影响GL 13 K活性。D-GL 13 K在革兰氏阳性菌中避开了两种耐药机制，而没有产生实质性的新耐药性。D-GL 13 K具有进一步开发抗生素的吸引力。
Antimicrobial peptides represent an alternative to traditional antibiotics that may be less susceptible to bacterial resistance mechanisms by directly attacking the bacterial cell membrane. However, bacteria have a variety of defense mechanisms that can prevent cationic antimicrobial peptides from reaching the cell membrane. The L- and D-enantiomers of the antimicrobial peptide GL13K were tested against the Gram-positive bacteria Enterococcus faecalis and Streptococcus gordonii to understand the role of bacterial proteases and cell wall modifications in bacterial resistance. GL13K was derived from the human salivary protein BPIFA2. Minimal inhibitory concentrations were determined by broth dilution and a serial assay used to determine bacterial resistance. Peptide degradation was determined in a bioassay utilizing a luminescent strain of Pseudomonas aeruginosa to detect peptide activity. Autolysis and D-alanylation-deficient strains of E. faecalis and S. gordonii were tested in autolysis assays and peptide activity assays. E. faecalis protease inactivated L-GL13K but not D-GL13K, whereas autolysis did not affect peptide activity. Indeed, the D-enantiomer appeared to kill the bacteria prior to initiation of autolysis. D-alanylation mutants were killed by L-GL13K whereas this modification did not affect killing by D-GL13K. The mutants regained resistance to L-GL13K whereas bacteria did not gain resistance to D-GL13K after repeated treatment with the peptides. D-alanylation affected the hydrophobicity of bacterial cells but hydrophobicity alone did not affect GL13K activity. D-GL13K evades two resistance mechanisms in Gram-positive bacteria without giving rise to substantial new resistance. D-GL13K exhibits attractive properties for further antibiotic development.
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影响因子：
3.2
作者：
Liu, Yaling;Burne, Robert A.
通讯作者：
Burne, Robert A.
影响因子：
3.9
作者：
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DOI：
10.1016/j.bbamem.2015.02.012
发表时间：
2015-11
期刊：
Biochimica et biophysica acta
影响因子：
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通讯作者：
Shafer WM
影响因子：
4.9
作者：
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通讯作者：
Gorr, Sven-Ulrik
影响因子：
3.7
作者：
Cole JN;Nizet V
通讯作者：
Nizet V