Abstract
The worldwide increase in antibiotic-resistant pathogens means that identification of alternative antibacterial drug targets and the subsequent development of new treatment strategies are urgently required. One such new target is the quorum sensing (QS) system. Coral microbial consortia harbor an enormous diversity of microbes, and are thus rich sources for isolating novel bioactive and pharmacologically valuable natural products. However, to date, the versatility of their bioactive compounds has not been broadly explored. In this study, about two hundred bacterial colonies were isolated from a coral species (Pocillopora damicornis) and screened for their ability to inhibit QS using the bioreporter strain Chromobacterium violaceum ATCC 12472. Approximately 15% (30 isolates) exhibited anti-QS activity, against the indicator strain. Among them, a typical Gram-positive bacterium, D11 (Staphylococcus hominis) was identified and its anti-QS activity was investigated. Confocal microscopy observations showed that the bacterial extract inhibited the biofilm formation of clinical isolates of wild-type P. aeruginosa PAO1 in a dose-dependent pattern. Chromatographic separation led to the isolation of a potent QS inhibitor that was identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) spectroscopy as DL-homocysteine thiolactone. Gene expression analyses using RT-PCR showed that strain D11 led to a significant down-regulation of QS regulatory genes (lasI, lasR, rhlI, and rhlR), as well as a virulence-related gene (lasB). From the chemical structure, the target compound (DL-homocysteine thiolactone) is an analog of the acyl-homoserine lactones (AHLs), and we presume that DL-homocysteine thiolactone outcompetes AHL in occupying the receptor and thereby inhibiting QS. Whole-genome sequence analysis of S. hominis D11 revealed the presence of predicted genes involved in the biosynthesis of homocysteine thiolactone. This study indicates that coral microbes are a resource bank for developing QS inhibitors and they will facilitate the discovery of new biotechnologically relevant compounds that could be used instead of traditional antibiotics.
Highlights
The rising problem of microbial resistance to current antibiotics and high spreading rate of resistant bacterial species has become a major public health concern
We uncovered the anti-quorum sensing (QS) activity of a marine bacterial species isolated from the coral Pocillopora damicornis
The extract of strain D11 (S. hominis) was antagonistic to P. aeruginosa PAO1 QS and affected QS-regulated functional genes, including those involved in biofilm formation and virulence production
Summary
The rising problem of microbial resistance to current antibiotics and high spreading rate of resistant bacterial species has become a major public health concern. Inhibition of QS is one of the many different strategies deployed to control biofilmforming microbes without causing drug resistance (Singh et al, 2013, 2016) Some opportunistic pathogens, such as Serratia marcescens and Pseudomonas aeruginosa, control production of their virulence factors including biofilm formation by using QS systems. Much work has focused on targeting microbial pathogenesis by inhibiting QS or biofilm formation This paradigm is neither bactericidal (it does not kill bacteria) nor bacteriostatic (it does not inhibit bacterial growth). It appears to be a attractive alternative to other methods because it does not impose a strong selective pressure, and bacterial resistance is less likely to develop (Sommer et al, 2013) For this reason, the identification of compounds that interfere with QS systems is of considerable interest in an effort to develop treatments against biofilm-associated pathogens (Christensen et al, 2007). An approach known as QS inhibition has been developed when an efficient screening for anti-QS agents is required
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
