Paeoniflorin reduce luxS/AI-2 system-controlled biofilm formation and virulence in Streptococcus suis

ABSTRACT Streptococcus suis (S. suis), more specifically serotype 2, is a bacterial pathogen that threatens the lives of pigs and humans. Like many other pathogens, S. suis exhibits quorum sensing (QS) system-controlled virulence factors, such as biofilm formation that complicates treatment. Therefore, impairing the QS involving LuxS/AI-2 cycle in S. suis, may be a promising alternative strategy for overcoming S. suis infections. In this study, we investigated paeoniflorin (PF), a monoterpenoid glycoside compound extracted from peony, as an inhibitor of S. suis LuxS/AI-2 system. At a sub-minimal inhibitory concentration (MIC) (1/16 MIC; 25 μg/ml), PF significantly reduced biofilm formation by S. suis through inhibition of extracellular polysaccharide (EPS) production, without affecting bacterial growth. Moreover, evidence was brought that PF reduces AI-2 activity in S. suis biofilm. Molecular docking indicated that LuxS may be the target of PF. Monitoring LuxS enzymatic activity confirmed that PF had a partial inhibitory effect. Finally, we showed that the use of PF in a mouse model can relieve S. suis infections. This study highlighted the anti-biofilm potential of PF against S. suis, and brought evidence that it may as an inhibitor of the LuxS/AI-2 system to prevent S. suis biofilm-related infections. PF can thus be used as a new type of natural biofilm inhibitor for clinical application.

[1]  Yu Yang,et al.  Effect of Syringopicroside Extracted from Syringa oblata Lindl on the Biofilm Formation of Streptococcus suis , 2021, Molecules.

[2]  L. Yi,et al.  The otc gene of Streptococcus suis plays an important role in biofilm formation, adhesion, and virulence in a murine model. , 2020, Veterinary microbiology.

[3]  J. Tian,et al.  Dissecting signal molecule AI-2 mediated biofilm formation and environmental tolerance in Lactobacillus plantarum. , 2020, Journal of bioscience and bioengineering.

[4]  Xiang Li,et al.  Antimicrobial and antibiofilm activities of paeoniflorin against carbapenem‐resistant Klebsiella pneumoniae , 2019, Journal of applied microbiology.

[5]  L. Yi,et al.  Autoinducer-2 influences tetracycline resistance in Streptococcus suis by regulating the tet(M) gene via transposon Tn916. , 2019, Research in veterinary science.

[6]  Xuezhang Zhou,et al.  Total alkaloids of Sophora alopecuroides and matrine inhibit auto-inducer 2 in the biofilms of Staphylococcus epidermidis. , 2019, Microbial pathogenesis.

[7]  E. Gilbert,et al.  Rhamnus prinoides (gesho): A source of diverse anti-biofilm activity. , 2019, Journal of ethnopharmacology.

[8]  L. Piddock,et al.  Non-traditional Antibacterial Therapeutic Options and Challenges. , 2019, Cell host & microbe.

[9]  M. Donia,et al.  Potential of marine natural products against drug-resistant bacterial infections. , 2019, The Lancet. Infectious diseases.

[10]  A. Netrusov,et al.  Composition of the Biofilm Matrix of Cutibacterium acnes Acneic Strain RT5 , 2019, Front. Microbiol..

[11]  M. Oves,et al.  Bougainvillea flower extract mediated zinc oxide's nanomaterials for antimicrobial and anticancer activity. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[12]  L. Yi,et al.  LuxS/AI-2 system is involved in fluoroquinolones susceptibility in Streptococcus suis through overexpression of efflux pump SatAB. , 2019, Veterinary microbiology.

[13]  N. M. Hassimotto,et al.  Effect of Quercetin Rich Onion Extracts on Bacterial Quorum Sensing , 2019, Front. Microbiol..

[14]  G. Lebel,et al.  Antibacterial activity against porcine respiratory bacterial pathogens and in vitro biocompatibility of essential oils , 2019, Archives of Microbiology.

[15]  Bonnie L Bassler,et al.  Bacterial quorum sensing in complex and dynamically changing environments , 2019, Nature Reviews Microbiology.

[16]  Jie-ping Zhu,et al.  Developing natural products as potential anti-biofilm agents , 2019, Chinese Medicine.

[17]  Shaohui Wang,et al.  pdh modulate virulence through reducing stress tolerance and biofilm formation of Streptococcus suis serotype 2 , 2019, Virulence.

[18]  Jianrong Li,et al.  Identification of natural product compounds as quorum sensing inhibitors in Pseudomonas fluorescens P07 through virtual screening. , 2018, Bioorganic & medicinal chemistry.

[19]  Chengping Lu,et al.  Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model. , 2018, Journal of Visualized Experiments.

[20]  L. Yi,et al.  The LuxS/AI-2 system of Streptococcus suis , 2018, Applied Microbiology and Biotechnology.

[21]  Guanzhao Liang,et al.  Paeoniflorin augments systemic Candida albicans infection through inhibiting Th1 and Th17 cell expression in a mouse model , 2018, International immunopharmacology.

[22]  Sheng Chang,et al.  Three new monoterpene glycosides from oil peony seed cake , 2018 .

[23]  N. Fittipaldi,et al.  Critical Streptococcus suis Virulence Factors: Are They All Really Critical? , 2017, Trends in microbiology.

[24]  Yanhua Li,et al.  Rutin Inhibits Streptococcus suis Biofilm Formation by Affecting CPS Biosynthesis , 2017, Front. Pharmacol..

[25]  Zhe Ma,et al.  Streptococcus suis Serotype 2 Biofilms Inhibit the Formation of Neutrophil Extracellular Traps , 2017, Front. Cell. Infect. Microbiol..

[26]  Chengping Lu,et al.  Streptococcus suis small RNA rss04 contributes to the induction of meningitis by regulating capsule synthesis and by inducing biofilm formation in a mouse infection model. , 2017, Veterinary microbiology.

[27]  N. Tufenkji,et al.  Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa , 2016, Scientific Reports.

[28]  D. Grenier,et al.  Green tea catechins potentiate the effect of antibiotics and modulate adherence and gene expression in Porphyromonas gingivalis. , 2016, Archives of oral biology.

[29]  C. Ding,et al.  Crystal Structure and Identification of Two Key Amino Acids Involved in AI-2 Production and Biofilm Formation in Streptococcus suis LuxS , 2015, PloS one.

[30]  Yanhua Li,et al.  Emodin affects biofilm formation and expression of virulence factors in Streptococcus suis ATCC700794 , 2015, Archives of Microbiology.

[31]  J. Corander,et al.  Genomic signatures of human and animal disease in the zoonotic pathogen Streptococcus suis , 2015, Nature Communications.

[32]  Youjun Feng,et al.  Streptococcus suis infection , 2014, Virulence.

[33]  Chengping Lu,et al.  Overexpression of luxS Cannot Increase Autoinducer-2 Production, Only Affect the Growth and Biofilm Formation in Streptococcus suis , 2013, TheScientificWorldJournal.

[34]  Xu Zhou,et al.  Screening of Actinobacillus pleuropneumoniae LuxS Inhibitors , 2013, Current Microbiology.

[35]  Vipin Chandra Kalia,et al.  Quorum sensing inhibitors: an overview. , 2013, Biotechnology advances.

[36]  Chengping Lu,et al.  Comparative Proteomic Analysis of Streptococcus suis Biofilms and Planktonic Cells That Identified Biofilm Infection-Related Immunogenic Proteins , 2012, PloS one.

[37]  Yang Wang,et al.  Functional analysis of luxS in Streptococcus suis reveals a key role in biofilm formation and virulence. , 2011, Veterinary microbiology.

[38]  H. Flemming,et al.  The biofilm matrix , 2010, Nature Reviews Microbiology.

[39]  Youjun Feng,et al.  Uncovering newly emerging variants of Streptococcus suis, an important zoonotic agent. , 2010, Trends in microbiology.

[40]  Ernesto García,et al.  Versatility of the capsular genes during biofilm formation by Streptococcus pneumoniae. , 2009, Environmental microbiology.

[41]  Christopher M Waters,et al.  The Vibrio harveyi quorum-sensing system uses shared regulatory components to discriminate between multiple autoinducers. , 2006, Genes & development.

[42]  M. Surette,et al.  The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum‐sensing signal molecule , 2001, Molecular microbiology.