Bringing Antimicrobial Strategies to a New Level: The Quorum Sensing System as a Target to Control Streptococcus suis

Streptococcus suis (S. suis) is an important zoonotic pathogen. It mainly uses quorum sensing (QS) to adapt to complex and changeable environments. QS is a universal cell-to-cell communication system that has been widely studied for its physiological functions, including the regulation of bacterial adhesion, virulence, and biofilm formation. Quorum sensing inhibitors (QSIs) are highly effective at interfering with the QS system and bacteria have trouble developing resistance to them. We review the current research status of the S. suis LuxS/AI-2 QS system and QSIs. Studies showed that by inhibiting the formation of AI-2, targeting the LuxS protein, inhibiting the expression of luxs gene can control the LuxS/AI-2 QS system of S. suis. Other potential QSIs targets are summarized, which may be preventing and treating S. suis infections, including AI-2 production, transmission, LuxS protein, blockage of AI-2 binding to receptors, AI-2-mediated QS. Since antibiotics are becoming increasingly ineffective due to the emergence of resistant bacteria, including S. suis, it is thus critical to find new antibacterial drugs with different mechanisms of action. QSIs provide hope for the development of such drugs.

[1]  Jie Yu,et al.  Virtual screening and in vitro experimental verification of LuxS inhibitors from natural products for Lactobacillus reuteri. , 2022, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[2]  L. Yi,et al.  Paeoniflorin reduce luxS/AI-2 system-controlled biofilm formation and virulence in Streptococcus suis , 2021, Virulence.

[3]  H. Dupont,et al.  Potential role of probiotics in reducing Clostridioides difficile virulence: Interference with quorum sensing systems. , 2021, Microbial pathogenesis.

[4]  Aijaz Ahmad,et al.  Quorum Sensing - A Stratagem for Conquering Multi-Drug Resistant Pathogens. , 2020, Current pharmaceutical design.

[5]  L. Yi,et al.  Research progress of bacterial quorum sensing receptors: Classification, structure, function and characteristics. , 2020, The Science of the total environment.

[6]  S. Straus,et al.  Towards Robust Delivery of Antimicrobial Peptides to Combat Bacterial Resistance , 2020, Molecules.

[7]  Xuepeng Wang,et al.  LuxS/AI-2 Quorum Sensing System in Edwardsiella piscicida Promotes Biofilm Formation and Pathogenicity , 2020, Infection and Immunity.

[8]  L. Yi,et al.  Regulatory Mechanisms of the LuxS/AI-2 System and Bacterial Resistance , 2019, Antimicrobial Agents and Chemotherapy.

[9]  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.

[10]  W. Zeng,et al.  The AI-2/luxS Quorum Sensing System Affects the Growth Characteristics, Biofilm Formation, and Virulence of Haemophilus parasuis , 2019, Front. Cell. Infect. Microbiol..

[11]  R. Vinothkannan,et al.  Fructose furoic acid ester: An effective quorum sensing inhibitor against uropathogenic Escherichia coli. , 2018, Bioorganic chemistry.

[12]  Bonnie L. Bassler,et al.  SnapShot: Bacterial Quorum Sensing , 2018, Cell.

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

[14]  Ben-Dong Fu,et al.  Rutin inhibits quorum sensing, biofilm formation and virulence genes in avian pathogenic Escherichia coli. , 2018, Microbial pathogenesis.

[15]  T. Defoirdt.  Quorum-Sensing Systems as Targets for Antivirulence Therapy. , 2017, Trends in microbiology.

[16]  M. Zeng,et al.  Chemical composition, antimicrobial and anti-quorum sensing activities of pummelo peel flavonoid extract , 2017 .

[17]  Yugu Li,et al.  LuxS/AI-2 in Streptococcus agalactiae reveals a key role in acid tolerance and virulence. , 2017, Research in veterinary science.

[18]  Linzi Li,et al.  New bicyclic brominated furanones as potent autoinducer-2 quorum-sensing inhibitors against bacterial biofilm formation. , 2017, European journal of medicinal chemistry.

[19]  R. Srinivasan,et al.  In vitro antibiofilm efficacy of Piper betle against quorum sensing mediated biofilm formation of luminescent Vibrio harveyi. , 2017, Microbial pathogenesis.

[20]  J. Abrini,et al.  Medicinal plant products targeting quorum sensing for combating bacterial infections. , 2017, Asian Pacific journal of tropical medicine.

[21]  Haipeng Sun,et al.  AI-2 quorum sensing negatively regulates rbf expression and biofilm formation in Staphylococcus aureus. , 2017, International journal of medical microbiology : IJMM.

[22]  Jaehyun Sim,et al.  D-Galactose as an autoinducer 2 inhibitor to control the biofilm formation of periodontopathogens , 2016, Journal of Microbiology.

[23]  L. Fox,et al.  Bactericidal effects of Cinnamon cassia oil against bovine mastitis bacterial pathogens , 2016 .

[24]  Q. Sun.  Research Progress on Bacterial Quorum Sensing Inhibitors , 2016 .

[25]  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.

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

[27]  C. Ubeda,et al.  Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota. , 2015, Cell reports.

[28]  Xu-Bin Wei,et al.  Andrographolide interferes quorum sensing to reduce cell damage caused by avian pathogenic Escherichia coli. , 2014, Veterinary microbiology.

[29]  Shaosong Huang,et al.  inhibitory effects of citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella enteritidis. , 2014, Journal of food protection.

[30]  S. Castillo,et al.  2(5H)-Furanone, epigallocatechin gallate, and a citric-based disinfectant disturb quorum-sensing activity and reduce motility and biofilm formation of Campylobacter jejuni , 2014, Folia Microbiologica.

[31]  T. Coenye,et al.  Quorum sensing inhibitors: how strong is the evidence? , 2013, Trends in microbiology.

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

[33]  Knut Drescher,et al.  A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation , 2013, Proceedings of the National Academy of Sciences.

[34]  L. Soulère,et al.  N,N′-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers , 2013, International journal of molecular sciences.

[35]  K. Xavier,et al.  AI-2-mediated signalling in bacteria. , 2013, FEMS microbiology reviews.

[36]  C. Waters,et al.  A Tangled Web: Regulatory Connections between Quorum Sensing and Cyclic Di-GMP , 2012, Journal of bacteriology.

[37]  L. Eberl,et al.  Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing , 2012, Antimicrobial Agents and Chemotherapy.

[38]  Minyong Li,et al.  Recent progresses on AI-2 bacterial quorum sensing inhibitors. , 2012, Current medicinal chemistry.

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

[40]  W. Bentley,et al.  Synthetic analogs tailor native AI-2 signaling across bacterial species. , 2010, Journal of the American Chemical Society.

[41]  Claudia Schmidt-Dannert,et al.  Applications of quorum sensing in biotechnology , 2010, Applied Microbiology and Biotechnology.

[42]  William E Bentley,et al.  Cross species quorum quenching using a native AI-2 processing enzyme. , 2010, ACS chemical biology.

[43]  K. Janda,et al.  Revisiting AI-2 quorum sensing inhibitors: direct comparison of alkyl-DPD analogues and a natural product fimbrolide. , 2009, Journal of the American Chemical Society.

[44]  D. Pei,et al.  Inhibition of S-ribosylhomocysteinase (LuxS) by substrate analogues modified at the ribosyl C-3 position. , 2009, Bioorganic & medicinal chemistry.

[45]  Chengping Lu,et al.  Biological activity and identification of a peptide inhibitor of LuxS from Streptococcus suis serotype 2. , 2009, FEMS microbiology letters.

[46]  Minyong Li,et al.  A new phenothiazine structural scaffold as inhibitors of bacterial quorum sensing in Vibrio harveyi. , 2009, Biochemical and biophysical research communications.

[47]  V. Schramm,et al.  Transition state analogues of 5′-methylthioadenosine nucleosidase disrupt quorum sensing , 2009, Nature chemical biology.

[48]  K. Bernard,et al.  Meningitis Caused by Streptococcus suis Serotype 14, North America , 2009, Emerging infectious diseases.

[49]  Minyong Li,et al.  Inhibitors and antagonists of bacterial quorum sensing , 2009, Medicinal research reviews.

[50]  Chung-Dar Lu,et al.  Structure‐Based Discovery and Experimental Verification of Novel AI‐2 Quorum Sensing Inhibitors against Vibrio harveyi , 2008, ChemMedChem.

[51]  S. Pillai,et al.  Grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria. , 2008, International journal of food microbiology.

[52]  S. Arold,et al.  Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides , 2008, Nucleic acids research.

[53]  S. Pillai,et al.  Identification of ground beef-derived fatty acid inhibitors of autoinducer-2-based cell signaling. , 2008, Journal of food protection.

[54]  Vanessa Sperandio,et al.  Global Effects of the Cell-to-Cell Signaling Molecules Autoinducer-2, Autoinducer-3, and Epinephrine in a luxS Mutant of Enterohemorrhagic Escherichia coli , 2007, Infection and Immunity.

[55]  G. Evans,et al.  Structure and inhibition of a quorum sensing target from Streptococcus pneumoniae. , 2006, Biochemistry.

[56]  W. Verstraete,et al.  Quorum Sensing-Disrupting Brominated Furanones Protect the Gnotobiotic Brine Shrimp Artemia franciscana from Pathogenic Vibrio harveyi, Vibrio campbellii, and Vibrio parahaemolyticus Isolates , 2006, Applied and Environmental Microbiology.

[57]  C. Bell,et al.  Design and synthesis of substrate and intermediate analogue inhibitors of S-ribosylhomocysteinase. , 2006, Journal of medicinal chemistry.

[58]  T. Wood,et al.  Differential Gene Expression for Investigation of Escherichia coli Biofilm Inhibition by Plant Extract Ursolic Acid , 2005, Applied and Environmental Microbiology.

[59]  B. Bassler,et al.  Regulation of Uptake and Processing of the Quorum-Sensing Autoinducer AI-2 in Escherichia coli , 2005, Journal of bacteriology.

[60]  Z. Zhou,et al.  Synthesis of LuxS inhibitors targeting bacterial cell-cell communication. , 2004, Organic letters.

[61]  K. Appelt,et al.  Structure-based design, synthesis, and antimicrobial activity of purine derived SAH/MTA nucleosidase inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[62]  B. Bassler,et al.  Chemical synthesis of S-ribosyl-L-homocysteine and activity assay as a LuxS substrate. , 2003, Bioorganic & medicinal chemistry letters.

[63]  B. Bassler,et al.  The LuxS‐dependent autoinducer AI‐2 controls the expression of an ABC transporter that functions in AI‐2 uptake in Salmonella typhimurium , 2001, Molecular microbiology.

[64]  B. Bassler,et al.  Quorum sensing in bacteria. , 2001, Annual review of microbiology.

[65]  B. Bassler,et al.  Intercellular signalling in Vibrio harveyi: sequence and function of genes regulating expression of luminescence , 1993, Molecular microbiology.

[66]  K. Nealson,et al.  Bacterial bioluminescence: its control and ecological significance , 1979 .