2. Academic Validation
  3. Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study

Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study

  • Metabolites. 2022 Mar 15;12(3):246. doi: 10.3390/metabo12030246.
Said E Desouky 1 2,  Mohammed Abu-Elghait 1,  Eman A Fayed 3,  Samy Selim 4,  Basit Yousuf 2,  Yasuhiro Igarashi 5,  Basel A Abdel-Wahab 6 7,  Amnah Mohammed Alsuhaibani 8,  Kenji Sonomoto 2,  Jiro Nakayama 2
Affiliations

Affiliations

  • 1 Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo 11884, Egypt.
  • 2 Laboratory of Microbial Technology, Division of Systems Bioengineering, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
  • 3 Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt.
  • 4 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72341, Saudi Arabia.
  • 5 Biotechnology Research Center, Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
  • 6 Department of Medical Pharmacology, College of Medicine, Assiut University, Assiut 7111, Egypt.
  • 7 Department of Pharmacology, College of Pharmacy, Najran University, Najran 1988, Saudi Arabia.
  • 8 Department of Physical Sport Science, College of Education, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
PMID: 35323689 DOI: 10.3390/metabo12030246
Abstract

Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes' expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and its ortholog fsr quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A-D, BU-4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus. On the Other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the fsr quorum sensing system and the gelatinase production in E. faecalis at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both fsr and agr quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors.

Keywords

Enterococcus faecalis; Staphylococcus aureus; actinomycetales metabolites; agr system; anti-virulence compounds; fsr system; molecular docking; quorum sensing inhibitor; quorum sensing system.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z