Effect of a phthalate derivative purified from Bacillus zhangzhouensis SK4 on quorum sensing regulated virulence factors of Pseudomonas aeruginosa

Siddhi D Shah; Harsh Patel; Saklain Mustak Saiyad; Bhakti Bajpai

doi:10.1016/j.micpath.2024.106664

Effect of a phthalate derivative purified from Bacillus zhangzhouensis SK4 on quorum sensing regulated virulence factors of Pseudomonas aeruginosa

Microb Pathog. 2024 Apr 26:191:106664. doi: 10.1016/j.micpath.2024.106664. Online ahead of print.

Authors

Siddhi D Shah¹, Harsh Patel², Saklain Mustak Saiyad³, Bhakti Bajpai⁴

Affiliations

¹ Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), The CVM University, Vallabh Vidyanagar, Anand, 388121, Gujarat, India. Electronic address: Siddhi99.shah@gmail.com.
² Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), The CVM University, Vallabh Vidyanagar, Anand, 388121, Gujarat, India. Electronic address: patelharshj0606@gmail.com.
³ Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), The CVM University, Vallabh Vidyanagar, Anand, 388121, Gujarat, India. Electronic address: saklainsaiyad13@gmail.com.
⁴ Ashok & Rita Patel Institute of Integrated Study and Research in Biotechnology and Allied Sciences (ARIBAS), The CVM University, Vallabh Vidyanagar, Anand, 388121, Gujarat, India. Electronic address: bhaktibajpai@aribas.edu.in.

PMID: 38679245
DOI: 10.1016/j.micpath.2024.106664

Abstract

Pseudomonas aeruginosa causes life-threatening diseases and is resistant to almost all conventional antibiotics. The quorum sensing (QS) system of P. aeruginosa contributes to many pathogenic factors some of which are pigment production, motility, and biofilm. The disruption of quorum sensing system may be an impactful strategy to deal with infections. The present study investigates the anti-quorum sensing property of a bioactive molecule extracted from marine epibiotic bacteria present on the surface of seaweeds. Among all the isolates tested against monitor strain Chromobacterium violaceum (MTCC 2656), the one with the highest activity was identified as Bacillus zhangzhouensis SK4. The culture supernatant was extracted with chloroform which was then partially purified by TLC and column chromatography. The probable anti-QS compound was identified as 1,2-benzenedicarboxylic acid, bis (2-methylpropyl ester) by GC-MS and NMR analysis. The treatment of P. aeruginosa MCC 3457 with the lead compound resulted in the reduced production of pyocyanin, rhamnolipids, exopolysaccharide, biofilm, and motility. The observations of light and scanning electron microscopy also supported the biofilm inhibition. The lead compound showed synergism with the meropenem antibiotic and significantly reduced MIC. The molecular docking and pharmacokinetics study predicted 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl ester), a phthalate derivative as a good drug candidate. The molecular dynamics study was also performed to check the stability of the lead compound and LasR complex. Further, lead compounds did not exhibit any cytotoxicity when tested on human embryonic kidney cells. As per our knowledge, this is the first report on the anti-QS activity of B. zhangzhouensis SK4, indicating that epibiotic bacteria can be a possible source of novel compounds to deal with the multidrug resistance phenomenon.

Keywords: Anti-quorum sensing; Epibiotic bacteria; Multidrug resistance; Pseudomonas aeruginosa; Quorum sensing.