Elgamoudi Bassam A, Taha Taha, Korolik Victoria
Institute for Glycomics, Griffith University, Gold Coast QLD 4222, Australia.
Antibiotics (Basel). 2020 Nov 23;9(11):836. doi: 10.3390/antibiotics9110836.
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 , 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 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 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 () and D-alanine-D-alanine ligase () while D-serine was only able to decrease the transcript levels of . Our findings suggest that a combination of DAs could reduce biofilm formation, viability and persistence of through dysregulation of and
细菌病原体形成生物膜的能力是与其发病机制和传播相关的重要毒力机制。生物膜在不利环境条件下的生存中起着关键作用，充当微生物污染和抗生素耐药性的储存库。对于肠道病原体而言，生物膜被认为是通过食物链传播的一个促成因素，目前尚无已知的干预方法。在此，我们提出一种通过应用D-氨基酸（DAs）和L-氨基酸（LAs）来减少生物膜形成的非常规方法。我们发现，除L-丙氨酸外，DAs而非LAs可将生物膜形成减少多达70%。用DAs处理细胞改变了生物膜结构并减少了淀粉样纤维的出现。此外，与单独使用D-环丝氨酸（DCS）处理相比，DAs混合物可将DCS的抗菌效力提高多达32%。出乎意料的是，D-丙氨酸能够逆转其他DAs以及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-丝氨酸仅能降低的转录水平。我们的研究结果表明，DAs组合可通过失调和来减少生物膜形成、的活力和持久性
