Inhibition of Campylobacter jejuni Biofilm Formation by D-Amino Acids.

Inhibition of Campylobacter jejuni Biofilm Formation by D-Amino Acids.
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DOI:
10.3390/antibiotics9110836
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发表时间:
2020-11-23
期刊:
Antibiotics (Basel, Switzerland)
影响因子:
--
通讯作者:
Korolik V
Korolik V
中科院分区:
其他
文献类型:
--
作者:
Elgamoudi BA;Taha T;Korolik V

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细菌病原体形成生物膜的能力是其致病和传播的重要毒力机制。生物膜是微生物污染和抗生素耐药性的储存库,在恶劣环境条件下的生存起着至关重要的作用。对于肠道病原体空肠弯曲杆菌,生物膜被认为是通过食物链传播的一个促成因素,目前还没有已知的干预方法。在这里,我们提出了一种非常规的方法,通过应用D-氨基酸(DAS)和L-氨基酸(LAS)来减少空肠弯曲菌的生物被膜形成。我们发现,除L-丙氨酸外,DAS而不是LAS能减少高达70%的生物膜形成。用DAS处理空肠弯曲菌细胞,改变了生物膜的结构,减少了淀粉样纤维的出现。此外,与D-环丝氨酸(DC)单独处理相比,DAS的混合物将D-环丝氨酸(DC)的抗菌效果提高了32%。出乎意料的是,D-丙氨酸能够逆转其他Das和DCs的抑制作用。此外,L-丙氨酸和D-色氨酸降低了肽聚糖生物合成酶丙氨酸消旋酶和D-丙氨酸-D-丙氨酸连接酶的转录水平,而D-丝氨酸仅能降低ALR的转录水平。我们的研究结果表明,DAS的联合作用可能通过调节ALR和ddlA来减少空肠弯曲菌的生物被膜形成、生存能力和持久性。
The ability of bacterial pathogens to form biofilms is an important virulence mechanism in relation to their pathogenesis and transmission. Biofilms play a crucial role in survival in unfavorable environmental conditions, acting as reservoirs of microbial contamination and antibiotic resistance. For intestinal pathogen Campylobacter jejuni, biofilms are considered to be a contributing factor in transmission through the food chain and currently, there are no known methods for intervention. Here, we present an unconventional approach to reducing biofilm formation by C. jejuni by the application of D-amino acids (DAs), and L-amino acids (LAs). We found that DAs and not LAs, except L-alanine, reduced biofilm formation by up to 70%. The treatment of C. jejuni cells with DAs changed the biofilm architecture and reduced the appearance of amyloid-like fibrils. In addition, a mixture of DAs enhanced antimicrobial efficacy of D-Cycloserine (DCS) up to 32% as compared with DCS treatment alone. Unexpectedly, D-alanine was able to reverse the inhibitory effect of other DAs as well as that of DCS. Furthermore, L-alanine and D-tryptophan decreased transcript levels of peptidoglycan biosynthesis enzymes alanine racemase (alr) and D-alanine-D-alanine ligase (ddlA) while D-serine was only able to decrease the transcript levels of alr. Our findings suggest that a combination of DAs could reduce biofilm formation, viability and persistence of C. jejuni through dysregulation of alr and ddlA.
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