Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou 570311, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
J Appl Microbiol. 2024 Sep 2;135(9). doi: 10.1093/jambio/lxae240.
Aeromonas hydrophila, a Gram-negative bacterium, is ubiquitously found in many aquatic habitats, causing septicemia in humans and fishes. Attributed to abuse or misuse of conventional antimicrobial drug usage, antimicrobial resistance is at an alarming rise. There is an available alternative strategy to bacterial resistance to antimicrobials, which is inhibition of virulence and pathogenicity employing quorum sensing inhibitors (QSIs). Hence, actinomycin D's effectiveness against A. hydrophila SHAe 115 as a QSI was investigated in decreasing virulence factors and preventing biofilm formation.
Actinomycin D, belongs to the QSI combating Pseudomonas aeruginosa PAO1 originally isolated from an entophytic actinomycete (Streptomyces cyaneochromogenes RC1) in Areca catechu L. In the present work, further investigations were carried out to assess the effect of actinomycin D at subminimal inhibitory concentrations (sub-MICs), QS-regulated virulence factors, and biofilm inhibition strategies. Intrinsic properties encompassing inhibition of the production of protease and hemolysin and subsequent activities on biofilm formation and eradication of mature biofilm were established along with weakened swimming and swarming motilities in A. hydrophila SHAe 115. In the Tenebrio molitor survival assay, actinomycin D effectively reduced the virulence and pathogenicity of A. hydrophila, resulting in elimination of mortality. However, the hydrolysate of actinomycin D, 2-hydroxy-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxylic acid (HDPD), had lost the QSI activity in A. hydrophila.
Actinomycin D was proved as a viable QSI in lessening A. hydrophila's the virulence and pathogenicity, as evident from our research findings.
气单胞菌是一种革兰氏阴性细菌,广泛存在于许多水生环境中,可导致人类和鱼类败血症。由于常规抗菌药物的滥用或误用,抗菌药物耐药性正在急剧上升。有一种替代细菌对抗生素耐药性的策略,即使用群体感应抑制剂 (QSIs) 抑制毒力和致病性。因此,研究了放线菌素 D 作为 QSI 对 SHAe 115 型嗜水气单胞菌的有效性,以减少毒力因子并防止生物膜形成。
放线菌素 D 最初是从槟榔内生放线菌(链霉菌蓝黑变种 RC1)中分离出来的,属于对抗铜绿假单胞菌 PAO1 的 QSI。在本工作中,进一步研究了放线菌素 D 在亚最小抑菌浓度 (sub-MIC) 下、QS 调节的毒力因子和生物膜抑制策略的作用。研究了放线菌素 D 的内在特性,包括抑制蛋白酶和溶血素的产生以及随后对生物膜形成和成熟生物膜消除的影响,以及嗜水气单胞菌 SHAe 115 的游动和群集运动能力减弱。在黄粉虫生存试验中,放线菌素 D 有效降低了嗜水气单胞菌的毒力和致病性,从而消除了死亡率。然而,放线菌素 D 的水解产物 2-羟基-4,6-二甲基-3-氧代-3H-苯并恶嗪-1,9-二羧酸(HDPD)在嗜水气单胞菌中失去了 QSI 活性。
根据我们的研究结果,放线菌素 D 被证明是一种有效的 QSI,可以减轻嗜水气单胞菌的毒力和致病性。