These findings indicated that PABA could be a candidate inhibitor of anthranilic acid signaling to interfere with the QS systems of R. solanacearum to attenuate the virulence and presented a non-antibiotic-based treatment strategy and provided a theoretical basis for the development of novel antibacterial treatment.
Abstract
ABSTRACT Quorum sensing (QS) is widely involved in the regulation of the biological functions and pathogenic processes of bacteria in a cell density-dependent manner. The anthranilic acid signal is directly sensed by the receptor RaaR, a transcription regulator, to control the expression level of downstream target genes in Ralstonia solanacearum, thus affecting the QS signals generation and the bacterial virulence. Here, we reported that 4-Aminobenzoic acid (PABA), a structural analogue of anthranilic acid, not only significantly inhibited the production of extracellular polysaccharides (EPS), biofilm formation, and motility of R. solanacearum, but also reduced the expression level of QS signaling molecules. We also found that PABA can directly bind to RaaR and prevented it from interacting with the promoters of target genes associated with the QS system and virulence of R. solanacearum. Point mutations in RaaR at residues F137 and I270 abolished the binding between RaaR and PABA, indicating that these two amino acid residues are likely critical for the interaction between RaaR and PABA. These findings indicated that PABA could be a candidate inhibitor of anthranilic acid signaling to interfere with the QS systems of R. solanacearum to attenuate the virulence. Together, our work presented a non-antibiotic-based treatment strategy and provided a theoretical basis for the development of novel antibacterial treatment.
The bacterial Quorum Sensing system refers to the recognition of signaling molecules called autoinducers produced by bacteria when a certain cell density is reached in the environment. Those cell-density-dependent autoinducers regulate and coordinate diverse functional processes, such as bioluminescence, biofilm production, sporulation, and even the expression of some virulence factors, among others. There is a wide variety of autoinducers, and for Gram-negative bacteria, the canonical autoinducers are the N-acyl-homoserine lactones (AI-1). Presently, the production of autoinducers in Leptospira has not been described; therefore, the objective of this study was to detect and identify autoinducers in this bacterial genus. We report here the expression of AI-1 in cultures ≥2.4 × 108 of Leptospira meyeri. Ethyl acetate extracts of Leptospira culture supernatants were capable of activating the β-galactosidase system in the biosensor Agrobacterium tumefaciens strain NTL4. Partial identification of the leptospiral supernatant extracts was done by thin-layer chromatography (TLC), showing a similar retention factor to the synthetic standard N-Octanoyl-DL-homoserine lactone (C8-AHL) in the Leptospira supernatant extracts. In addition, infrared spectroscopy (IR) analysis showed peaks corresponding to the lactone and amide groups in both the C8-AHL standard and the Leptospira meyeri culture extracts. Moreover, High-Performance Liquid Chromatography–Mass Spectrometry (HPLC-MS/MS) confirmed the same retention time (10.7 ± 0.1 min) in both the Leptospira meyeri supernatant extracts and the C8-AHL standard. These results show that Leptospira meyeri synthesizes N-acyl homoserine lactone family autoinducers, particularly the N-Octanoyl-DL-homoserine lactone, and lay the groundwork for future research on Quorum Sensing systems in Leptospira.
Luz Olivia Castillo-Sánchez, A. de la Peña-Moctezuma, G. Bautista-Trujillo et al.· Microorganisms· 0 citations
This study provides novel and unexpected insights into the involvement of a LuxR homolog in regulating a QS system in Gram-positive bacteria and demonstrates that functional GBL-based QS systems are conserved and active in R. erythropolis.
Héloïse Bizière-Maco, Nathan Jordier, J. F. Barbosa-de-Bessa et al.· Frontiers in Microbiology· 0 citations
This review highlights recent advances in the development of sulfonyl- and sulfinyl-containing organosulfur compounds as modulators of QS and biofilm formation in clinically relevant Gram-negative pathogens.
D. Nwobodo, M. Egbujor, Samuel S. Kiprotich et al.· FEMS Microbiology Reviews· 0 citations
While strain XJ-10 showed no detectable acylase activity, it exhibited significant degradation activity against AHL, suggesting a distinct QQ mechanism, and these findings broaden the scope of QQ-based biocontrol strategies and enhance mechanistic insights into managing bacterial diseases through QS modulation.
We present a novel strategy for the inhibition of quorum sensing in Staphylococcus bacteria. Previous work has focused on the development of peptides that can compete with native autoinducing peptides (AIPs), to antagonize the receptor histidine kinase responsible for activation of quorum sensing and thereby repress the expression of virulence genes. Here we report simple analogues of cysteine that can eliminate the native AIPs extracellularly, before they activate their receptor, and validate that this alternative strategy can also be applied to turn off quorum sensing in different Staphylococcus aureus reporter strain assays. Further, we show that two selected compounds can reduce skin infection caused by MRSA in a murine model. This work provides impetus for the development of simple small molecules for the topical treatment of staphylococcal skin infections. We anticipate that further studies, including delivery strategies, will help illuminate this potential.
Bengt H. Gless, Riccardo Milazzo, M. Bojer et al.· Angewandte Chemie· 0 citations