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Fulltext The Effects of Chinese Herbal Medicines on the Quorum Sensing-Regulated Virulence in Pseudomonas aeruginosa PAO1

Chong YM, How KY, Yin WF, Chan KG

Molecules, 2018 04 21;23(4).
PMID: 29690523 DOI: 10.3390/molecules23040972

The quorum sensing (QS) system has been used by many opportunistic pathogenic bacteria to coordinate their virulence determinants in relation to cell-population density. As antibiotic-resistant bacteria are on the rise, interference with QS has been regarded as a novel way to control bacterial infections. As such, many plant-based natural products have been widely explored for their therapeutic roles. These natural products may contain anti-QS compounds that could block QS signals generation or transmission to combat QS pathogens. In this study, we report the anti-QS activities of four different Chinese herbal plant extracts: Poria cum Radix pini, Angelica dahurica, Rhizoma cibotii and Schizonepeta tenuifolia, on Pseudomonas aeruginosa PAO1. All the plants extracted using hexane, chloroform and methanol were tested and found to impair swarming motility and pyocyanin production in P.aeruginosa PAO1, particularly by Poria cum Radix pini. In addition, all the plant extracts also inhibited violacein production in C.violaceum CV026 up to 50% while bioluminescence activities were reduced in lux-based E. coli biosensors, pSB401 and pSB1075, up to about 57%. These anti-QS properties of the four medicinal plants are the first documentation that demonstrates a potential approach to attenuate pathogens’ virulence determinants.

Matched MeSH terms: Virulence/drug effects
Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum

Gemiarto AT, Ninyio NN, Lee SW, Logis J, Fatima A, Chan EW, et al.

Antonie Van Leeuwenhoek, 2015 Aug;108(2):491-504.
PMID: 26059863 DOI: 10.1007/s10482-015-0503-6

The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M-H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.

Matched MeSH terms: Virulence/drug effects
Oxidative stress resistance and fitness-compensatory response in vancomycin-intermediate Staphylococcus aureus (VISA)

Tan XE, Neoh HM, Cui L, Hiramatsu K, Jamal R

Can J Microbiol, 2019 Aug;65(8):623-628.
PMID: 31063703 DOI: 10.1139/cjm-2019-0048

In this study, vancomycin-intermediate Staphylococcus aureus (VISA) cells carrying vraS and (or) graR mutations were shown to be more resistant to oxidative stress. Caenorhabditis elegans infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appear to be physiological adaptations associated with the VISA phenotype in the Mu50 lineage.

Matched MeSH terms: Virulence/drug effects
Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases

Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, et al.

Expert Rev Anti Infect Ther, 2021 05;19(5):571-586.
PMID: 33131352 DOI: 10.1080/14787210.2021.1843427

INTRODUCTION: Quorum-sensing (QS) is a microbial cell-to-cell communication system that utilizes small signaling molecules to mediates interactions between cross-kingdom microorganisms, including Gram-positive and -negative microbes. QS molecules include N-acyl-homoserine-lactones (AHLs), furanosyl borate, hydroxyl-palmitic acid methylester, and methyl-dodecanoic acid. These signaling molecules maintain the symbiotic relationship between a host and the healthy microbial flora and also control various microbial virulence factors. This manuscript has been developed based on published scientific papers.
AREAS COVERED: Furanones, glycosylated chemicals, heavy metals, and nanomaterials are considered QS inhibitors (QSIs) and are therefore capable of inhibiting the microbial QS system. QSIs are currently being considered as antimicrobial therapeutic options. Currently, the low speed at which new antimicrobial agents are being developed impairs the treatment of drug-resistant infections. Therefore, QSIs are currently being studied as potential interventions targeting QS-signaling molecules and quorum quenching (QQ) enzymes to reduce microbial virulence.
EXPERT OPINION: QSIs represent a novel opportunity to combat antimicrobial resistance (AMR). However, no clinical trials have been conducted thus far assessing their efficacy. With the recent advancements in technology and the development of well-designed clinical trials aimed at targeting various components of the, QS system, these agents will undoubtedly provide a useful alternative to treat infectious diseases.

Matched MeSH terms: Virulence/drug effects
Fulltext The higher prevalence of extended spectrum beta-lactamases among Escherichia coli ST131 in Southeast Asia is driven by expansion of a single, locally prevalent subclone

Chen SL, Ding Y, Apisarnthanarak A, Kalimuddin S, Archuleta S, Omar SFS, et al.

Sci Rep, 2019 09 13;9(1):13245.
PMID: 31519972 DOI: 10.1038/s41598-019-49467-5

The ST131 multilocus sequence type (MLST) of Escherichia coli is a globally successful pathogen whose dissemination is increasing rates of antibiotic resistance. Numerous global surveys have demonstrated the pervasiveness of this clone; in some regions ST131 accounts for up to 30% of all E. coli isolates. However, many regions are underrepresented in these published surveys, including Africa, South America, and Asia. We collected consecutive bloodstream E. coli isolates from three countries in Southeast Asia; ST131 was the most common MLST type. As in other studies, the C2/H30Rx clade accounted for the majority of ST131 strains. Clinical risk factors were similar to other reported studies. However, we found that nearly all of the C2 strains in this study were closely related, forming what we denote the SEA-C2 clone. The SEA-C2 clone is enriched for strains from Asia, particularly Southeast Asia and Singapore. The SEA-C2 clone accounts for all of the excess resistance and virulence of ST131 relative to non-ST131 E. coli. The SEA-C2 strains appear to be locally circulating and dominant in Southeast Asia, despite the intuition that high international connectivity and travel would enable frequent opportunities for other strains to establish themselves.

Matched MeSH terms: Virulence/drug effects*
Fulltext Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S

BMC Complement Altern Med, 2014;14:4.
PMID: 24393217 DOI: 10.1186/1472-6882-14-4

The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.

Matched MeSH terms: Virulence/drug effects