A WAY OF COMBATING ANTIMICROBIAL RESISTANCE THROUGH QUORUM SENSING

A WAY OF COMBATING ANTIMICROBIAL RESISTANCE THROUGH QUORUM SENSING

Shabnam Thakur *, Rupali Sharma and Rakesh Yadav

Amity Institute of Pharmacy, Amity University Haryana, Manesar, Gurgaon, Haryana, India.

ABSTRACT: Quorum sensing is a peculiar mechanism of microbial communication through the induction of various signalling autoinducer molecules having several gene expression regulatory activities of different virulence factors that control microbial. This enables a systematic path of inhibiting microbial growth and its infection production efficacy by indirectly regulating the Quorum sensing activity of the concerned pathogens. As antimicrobial resistance directly impacts the healthcare system, hence is one of the biggest threats to global health. The attenuation or inactivation of these resistant variety bacteria is the utmost call of hour. In this panorama, interference/change in the chemical signal of QS system has been developed as an efficient technique to block their expression, hence enabling them as less virulent. A literature study was performed using online research, including database searches such as PubMed, SciELO, and SCOPUS between 2000-2020. This review aims to provide a brief mechanism of inhibition of microbial resistance through QS system by different strategies.

Keywords: Anti-QS molecules, Bacterial Efflux Pump, Microbial resistant, Signalling molecules, Quorum sensing

INTRODUCTION: The breakthrough insight for the generation of neo-antibiotics and their ruthless utilization led to a major crisis in the human world; where the pathogenic microbes have developed resistance against more and/or all the available antibiotics leading to the development of multi-drug resistant (MDR) strains of pathogens ^{1, 2}. To inhibit or regulate their growth, several physiological processes have been adopted that kill the pathogen by destroying its protein bio-synthesis mechanism or disrupting its membrane structures. However, the increased use of antibiotics indirectly helps the microbes generate resistant pathogenic varieties ³ that cause severe health havoc in today’s healthcare system ⁴.

Three vital techniques have developed the resistant efficacy of microbes, viz. chemical modification of antibiotics by secretion of certain alternative enzymes to degrade the concerning antibiotics and attenuate its efficacy by scattering the functional groups ⁵, efflux pump (lipophilic and/or hydrophilic efflux pump) activation by microbes on the cell membrane that systematically removes desired antibiotics, which is done by higher excretion rate compared to the drug penetration rate to regulate the concentration of the antibiotics as minimum as possible ⁶ and alternation in the drug-targeting genes by modification of targeted gene or interference with the targeted site so that the antibiotic target will be lost ⁷.

In pathogenic microbes, especially in bacteria, some kind of extracellular chemical signalling molecules, called auto-inductors are being secreted that interact with the receptor protein leading to coordinated changes in the expression of specific genes to counteract the activities of antibiotics ⁸. Precisely Quorum sensing (QS) is a mechanism that enables microbial interaction based on the secretion of auto inductors to the environment ⁹. This developed mechanism of bacteria has machinated complex tools to inhibit the disruption of concerned microbes leading to the increased population of MDR strains, as it mostly regulates maximum cellular metabolic functions of microorganisms, including pathogenic gene expression, toxin production and elevating drug efflux system and microbial biofilms formation ¹⁰.

Bacterial efflux pump systems that effectively drop off antibiotics into the bacteria are mostly regulated by QS systems ^{11, 12}. The QS regulation mechanism involves both up-regulations of MDR pump MexAB-OprM, causing the development of MDR bacterial strain ¹³ along with some impact on the QS system itself ¹⁴. As bacterial biofilms have a direct relation with their resistance, regulation of bacterial biofilm formation by QS can directly affect the resistance efficacy of the concerned microbe ¹⁵, achieved by incurring nutrition restriction ¹⁶ and drug resistance phenotypic methods ¹⁷. Pathogenic bacteria secrete certain proteins as toxins that kill other microbes and damage the host immune system, which is transported by several secretory systems ¹⁸. The regulation of these secretory systems can prevent the resistant efficacy of the concerned bacteria. The type I secretion system (T1SS), present in Gram-negative bacteria, is regulated by the Has system of Serratia marcescens and Pseudomonas aeruginosa, and the hemolysin system of Vibrio cholerae, Neisseria meningitidis and E. coli ¹⁹. Similarly, the type II secretion system (T2SS), present in Gram-negative bacteria, is regulated by Xcp system of P. aeruginosa ²⁰. As the QS system plays a pivotal role in inhibiting bacterial-resistant variety development, the resistant efficacy of that microbe can be suppressed by interfering with the QS system of the desired microbe. However, in this meta-analysis, a brief comparative study regarding the different QS system inhibition strategies has been elaborately described.

MATERIALS AND METHODS:

Source: For the process of meta-analysis at the initial stage, three major research databases, namely SCOPUS, PubMed, Science Direct were searched in order to collect related articles. However, almost all the articles found in the PubMed and Science Direct databases were available in the Scopus database as well, and therefore SCOPUS database was used as the source for the collection of primary data for the review. The articles were selected from the database using relevant keywords like “Quorum sensing”, “Microbial resistance”, “Quorum quenching”, “Regulation of Bacterial Efflux Pump by QS”, “Regulation of Bacterial Biofilm Formation by QS”, “Regulation of Bacterial Secretion System by QS” etc. These collected research papers were inspected thoroughly for further analysis.

Data Extraction: After identifying the core theme, the papers selected under the themes were subjected to extensive reading. To prevent bias in the selection of papers, “The Preferred Reporting Items for Systematic Review and Meta-Analysis” (PRISMA) flow chart has then been prepared to demarcate the inclusion and exclusion criteria for the selected papers. The SCOPUS database was also used to obtain various bibliometric trends which were used to analyze various perceptive of research contributions under the selected research topic.

RESULT & DISCUSSION: The excessive use of antimicrobial drugs has paved the path for the microbes to generate and sustain the generalized threat and helps in adopting, to be more précised, creating the multidrug-resistant (MDR) strains. This creates a major threat to mankind as most of the present drugs remain inactivated for treating them ²¹. To solve this issue, regulation of Quorum sensing (QS) Signalling molecules can play a vital role as it has direct control over all the virulent factors of the microbe within the host body. The regulation of QS-secreted auto inductors not only means inhibition of concerned molecules; however, this can also be achieved by degradation of signal molecules or inhibiting signal molecule conduction to the specific receptors ²². For this reason, excessive studies have been going on regulating the QS activity of microbes, thus controlling the infections caused by resistant strains. For the data extraction, the selected papers' key data were screened and analyzed on the following set of particulars: details of the authors with a year of publication, Test Organism; Strategy Mechanism; and Biological Effects.

These key data sets were summarized in the following table to ease further theme-wise analysis Table 1. Quorum sensing is an efficient mechanism that regulates the communal behaviour of microbes, mostly by controlling specific gene expression. In most microbial physiological pathways, such as exopolysaccharide and toxin production, biofilm formation is generally influenced by quorum sensing. However, quorum-sensing-interfering (QSI) compounds synthesized naturally and/or artificially have both positive and negative impacts on the microbial signalling network ²³.

TABLE 1: INHIBITION STRATEGIES OF QS SYSTEM

Many recent works focus on the indirect regulation of MDR strains by modifying the quorum-sensing signal molecules or synthesizing some structural analogues to those of concerned quorum-sensing signal molecules. Quorum sensing is a common practice for bacterial species to communicate with each other through specific gene regulation. This is achieved by the production of certain signal molecules called autoinducers. The microbial population directly impacts the amount of these signal molecule production ⁵⁸.

The alternation or change in signal molecules could be due to their degradation ^{36, 39, 41} or the addition of competitive inhibitor molecules that would block the signal molecule binding to receptors ^{47, 49-51}. Inhibition of quorum sensing signalling through inhibiting the AHL signal generation can be achieved in three ways viz. affecting the synthesis of the substrates for AHL synthase i.e., fattyacyl-acyl carrier protein (acyl-ACPs) by inhibitors; inhibiting N-acyl homoserine lactone (AHL) synthesis directly; and by inhibiting the HLAs transport ⁵⁹. In a study, Picomolar inhibitor, MT-DADMe-ImmA has been synthesized through 5′-methylthioadenosine phosphorylase (MTAP) that blocks QS in Vibrio cholerae without affecting growth rate and inhibits QS signal AI-2 ²⁵.

Similarly, regulation of quorum sensing by affecting the signal reception is also crucial and follows various ways. These are direct AHL degradation to limit signal turnover, segregation of the AHL signalling pathway, and competition on AHL receptors with suitable AHL-mimetic compounds. The degradation mechanism of signal molecules uses quorum-quenching enzymes produced by microbes leading to less concentration of signal molecules below the threshold. This will directly affect the microbial gene expression and generation of any virulent factors. A similar mechanism of QS regulation was followed where the aiiA gene degrades AHL encoding enzyme, thereby degrading AHL signalling molecules in Bacillus sp. 240B1 ³². The quorum-sensing system using AHL signal molecules degradation method for many pathogenic bacteria can be a vital virulence regulator. It showed greater efficacy as no regulation was imposed on the pathogen itself; however, their signal molecules are targeted. Moreover, Signal molecule attenuation or degradation can be achieved using QS to prevent bacterial resistance. Many microbes can metabolize AI-2, leading to the inhibition of QS function. AI-2 can be phosphorylated outside the cell by the addition of ATP and LsrK, which are then unable to pass through the cell membrane as QS signals ⁶⁰. This mechanism was widely accepted and backed up by several other studies ^39-41.

Moreover, quorum-inducing signal inhibitors also help in the reduction of pathogenicity. The addition of competitors achieves this. Many living organisms secrete several compounds that are quorum-sensing signal analogues and can competitively bind with microbial quorum-sensing signal receptors, thereby interfering with their regulation system. This leads to a decrease in the pathogenicity ²². Several studies showed similar results ^49-51. The study showed that the five different halo quinoneanaloguesin Cell culture and Xenopus embryos block the Wntsignalling downstream of beta-Catenin, thereby inhibiting the activated Wnt/β-catenin signalling ⁴³. Similarly, the anti-QS molecules can also help in diminishing the QS signalling, thereby preventing bacteria's pathogenicity, its resistant activity, and biofilm formation. It will directly block the development of drug-resistant to pathogens ^{53-57, 61}.

CONCLUSION: Bacterial quorum sensing (QS) signalling, consisting of acyl-homoserine lactones (AHLs), autoinducing peptides (AIPs), and autoinducer-2 (AI-2), plays a pivotal role in balancing its pathogenesis. The alternatives to antibiotics are in high demand nowadays due to the increase in the resistance factor of pathogens. The most suitable one currently is an alteration in the signal molecule production by several strategies, including their inhibition or degradation or blocking of receptor molecules or utilization of anti-QS agents. These methods help in the reduction of bacterial virulence, thereby inactivating them.

However, elaborate studies on this aspect provide an alternate method to suppress or degrade the virulence activity of microbes due to their increased multi-resistant capacity. Hence, multi-regulatory mechanisms have to be utilized in view of the current QS-related, related research should be further improved by means of molecular biology. The complex microbial drug resistance system should be well studied, and efficient QSI screening methods should be adopted. Multiple QS regulation compounds in bio-active compounds, suppressing elements, or targeting genes should be considered more.

The study related to the formation of microbial resistance mechanisms and their regulation through different strategies is the current approach that deals with the regulation of the quorum-sensing system. It not only has a role in microbial pathogenesis but has an active involvement in bacterial biofilm formation and its regulation. Hence breakthrough in research related to quorum sensing and its regulatory systems on microbial-resistant pathogenicity has several alternatives and are the main focused area for future research.

ACKNOWLEDGEMENT: The authors are very much thankful to Amity Institute of Pharmacy, Amity University, Gurgaon, India, for providing the necessary support to complete this work successfully.

CONFLICT OF INTEREST: All authors declared no conflicts of interest.

REFERENCES:

1. Hui CY, Guo Y, Liu L and Yi J: Recent advances in bacterial biosensing and bioremediation of cadmium pollution: a mini-review. World Journal of Microbiology and Biotechnology 2022; 38(1): 1-6.
2. Ali Q, Zheng H, Rao MJ, Ali M, Hussain A, Saleem MH, Nehela Y, Sohail MA, Ahmed AM, Kubar KA and Ali S: Advances, limitations, and prospects of biosensing technology for detecting phytopathogenic bacteria. Chemosphere 2022; 133773.
3. Ackermann J, Metternich JT, Herbertz S, Kruss S. Biosensing with Fluorescent Carbon Nanotubes. Angewandte Chemie International Edition 2022; 3.
4. Zhang NX, Guo Y, Li H, Yang XQ, Gao CX and Hui CY: Versatile artificial mer operons in Escherichia coli towards whole cell biosensing and adsorption of mercury. Plos one 2021; 16(5): 0252190.
5. Singh A and Kumar V: Recent advances in synthetic biology–enabled and natural whole-cell optical biosensing of heavy metals. Analytical and Bioanalytical Chemistry 2021; 413(1): 73-82.
6. Paluch E, Rewak-Soroczyńska J, Jędrusik I, Mazurkiewicz E and Jermakow K: Prevention of biofilm formation by quorum quenching. Applied Microbiology and Biotechnology 2020; 104(5): 1871-81.
7. Zhang W, Luo Q, Zhang Y, Fan X, Ye T, Mishra S, Bhatt P, Zhang L and Chen S: Quorum Quenching in a Novel Acinetobacter sp. XN-10 Bacterial Strain against Pectobacterium carotovorum carotovorum. Microorganisms 2020; 8(8): 1100.
8. Wei Q, Bhasme P, Wang Z, Wang L, Wang S, Zeng Y, Wang Y, Ma LZ and Li Y: Chinese medicinal herb extract inhibits PQS-mediated quorum sensing system in Pseudomonas aeruginosa. Journal of Ethnopharmacology 2020; 248: 112272.
9. Liao X, Ma Y, Daliri EB, Koseki S, Wei S, Liu D, Ye X, Chen S and Ding T: Interplay of antibiotic resistance and food-associated stress tolerance in food borne pathogens. Trends in Food Science & Technology 2020; 95: 97-106.
10. Cassini A, Högberg LD, Plachouras D, Quattrocchi A, Hoxha A, Simonsen GS, Colomb-Cotinat M, Kretzschmar ME, Devleesschauwer B, Cecchini M and Ouakrim DA: Burden of AMR Collaborative Group. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis 2019; 19(1): 56-66.
11. Ma Y, Lan G, Li C, Cambaza EM, Liu D, Ye X, Chen S and Ding T: Stress tolerance of Staphylococcus aureus with different antibiotic resistance profiles. Microbial Pathogenesis 2019; 133: 103549.
12. Subhadra B, Oh MH and Choi CH: RND efflux pump systems in Acinetobacter, with special emphasis on their role in quorum sensing. Journal of Bacteriology and Virol 2019; 49(1): 1-1.
13. Wang Y, Liu B, Grenier D and Yi L: Regulatory mechanisms of the LuxS/AI-2 system and bacterial resistance. Antimicrobial Agents and Chemotherapy 2019; 63(10): 01186-19.
14. Saxena P, Joshi Y, Rawat K and Bisht R: Biofilms: architecture, resistance, quorum sensing and control mechanisms. Indian J of Microbiology 2019; 59(1): 3-12.
15. Zhao X, Yu Z and Ding T: Quorum-sensing regulation of antimicrobial resistance in bacteria. Micro 2020; 8(3): 425.
16. Kalia M, Yadav VK, Singh PK, Dohare S, Sharma D, Narvi SS and Agarwal V: Designing quorum sensing inhibitors of Pseudomonas aeruginosa utilizing FabI: an enzymic drug target from fatty acid synthesis pathway. 3 Biotech 2019; 9(2): 1-0.
17. Zhang JW, Xuan CG, Lu CH, Guo S, Yu JF, Asif M, Jiang WJ, Zhou ZG, Luo ZQ and Zhang LQ: AidB, a novel thermostable N-acylhomoserine lactonase from the bacterium Bosea sp. Applied and Environmental Microbiology 2019; 85(24): e02065-19.
18. Wang J, Lin J, Zhang Y, Zhang J, Feng T, Li H, Wang X, Sun Q, Zhang X and Wang Y: Activity improvement and vital amino acid identification on the marine-derived quorum quenching enzyme MomL by protein engineering. Marine Drugs 2019; 17(5): 300.
19. Bortolotti D, Trapella C, Bragonzi A, Marchetti P, Zanirato V, Alogna A, Gentili V, Cervellati C, Valacchi G, Sicolo M and Turrin G: Conjugation of LasR quorum-sensing inhibitors with ciprofloxacin decreases the antibiotic tolerance of aeruginosa clinical strains. Journal of Chemistry 2019; 2019.
20. Yao J, Wang Y, Wu G, Sun M, Wang M and Zhang Q: Growth characteristics and properties of micro-arc oxidation coating on SLM-produced TC4 alloy for biomedical applications. Applied Surface Science 2019; 479: 727-37.
21. Abisado RG, Benomar S, Klaus JR, Dandekar AA, Chandler JR. Bacterial quorum sensing and microbial community interactions. MBio 2018; 9(3): 02331-17.
22. Bäuerle T, Fischer A, Speck T and Bechinger C: Self-organization of active particles by quorum sensing rules. Nature Communications 2018; 9(1): 1-8.
23. Alcalde-Rico M, Olivares-Pacheco J, Alvarez-Ortega C, Cámara M and Martínez JL: Role of the multidrug resistance efflux pump MexCD-OprJ in the Pseudomonas aeruginosa quorum sensing response. Frontiers in Microbiology 2018:2752.
24. Gohil N, Ramírez-García R, Panchasara H, Patel S, Bhattacharjee G and Singh V: Book review: quorum sensing vs. quorum quenching: a battle with no end in sight. Frontiers in Cellular and Infection Microbiology 2018; 8: 106.
25. Yu L, Li W, Zhang M, Cui Y, Chen X, Ni J, Yu L, Shang F and Xue T: Imidazole decreases the ampicillin resistance of an Escherichia coli strain isolated from a cow with mastitis by inhibiting the function of autoinducer 2. Journal of Dairy Science 2018; 101(4): 3356-62.
26. Sakr MM, Aboshanab KM, Elkhatib WF, Yassien MA: Hassouna NA: Over expressed recombinant quorum quenching lactonase reduces the virulence, motility and biofilm formation of multidrug-resistant Pseudomonas aeruginosa clinical isolates. Applied Microbiology and Biotechnology 2018; 102(24): 10613-22.
27. Dong W, Zhu J, Guo X, Kong D, Zhang Q, Zhou Y, Liu X, Zhao S and Ruan Z: Characterization of AiiK, an AHL lactonase, from Kurthiahuakui LAM0618T and its application in quorum quenching on Pseudomonas aeruginosa PAO1. Scientific Reports 2018; 8(1): 1-1.
28. Blöcher R, Rodarte Ramírez A, Castro-Escarpulli G, Curiel-Quesada E and Reyes-Arellano A: design, synthesis, and evaluation of Alkyl-Quinoxalin-2 (1H)-one derivatives as anti-quorum sensing molecules, inhibiting biofilm formation in Aeromonas caviae Molecules 2018; 23(12): 3075.
29. Torres M, Reina JC, Fuentes-Monteverde JC, Fernández G, Rodríguez J, Jiménez C and Llamas I: AHL-lactonase expression in three marine emerging pathogenic Vibrio spp. reduces virulence and mortality in brine shrimp (Artemia salina) and Manila clam (Venerupis philippinarum). PloS one 2018; 13(4): e0195176.
30. Guendouze A, Plener L, Bzdrenga J, Jacquet P, Rémy B, Elias M, Lavigne JP, Daudé D and Chabrière E: Effect of quorum quenching lactonase in clinical isolates of Pseudomonas aeruginosa and comparison with quorum sensing inhibitors. Frontiers in Microbiology 2017; 8: 227.
31. Fan X, Liang M, Wang L, Chen R, Li H, Liu X. Aii810, a novel cold-adapted N-acylhomoserine lactonase discovered in a metagenome, can strongly attenuate Pseudomonas aeruginosa virulence factors and biofilm formation. Frontiers in Microbiology 2017; 8: 1950.
32. Paczkowski JE, Mukherjee S, McCready AR, Cong JP, Aquino CJ, Kim H, Henke BR, Smith CD, Bassler BL. Flavonoids suppress Pseudomonas aeruginosa virulence through allosteric inhibition of quorum-sensing receptors. Journal of Biological Chemistry 2017; 292(10): 4064-76.
33. Lee J, Lee I, Nam J, Hwang DS, Yeon KM and Kim J: Immobilization and stabilization of acylase on carboxylated polyaniline nanofibers for highly effective antifouling application via quorum quenching. ACS Applied Materials & Interfaces 2017; 9(18): 15424-32.
34. Bouyahya A, Dakka N, Et-Touys A, Abrini J and Bakri Y: Medicinal plant products targeting quorum sensing for combating bacterial infections. Asian Pacific Journal of Tropical Medicine 2017; 10(8): 729-43.
35. Zhao X, Yu Z and Ding T: Quorum-sensing regulation of antimicrobial resistance in bacteria. Micro 2020; 8(3): 425.
36. Sauvage E and Terrak M: Glycosyl transferases and transpeptidases/penicillin-binding proteins: valuable targets for new antibacterials. Antibiotics 2016; 5(1): 12.
37. Avican U: Twin-arginine translocation in Yersinia: the substrates and their role in virulence (Doctoral dissertation, Umeå University).
38. Maura D, Hazan R, Kitao T, Ballok AE and Rahme LG: Evidence for direct control of virulence and defense gene circuits by the Pseudomonas aeruginosa quorum sensing regulator, MvfR. Scientific Reports 2016; 6(1): 1-4.
39. Donati ER: editor. Heavy metals in the environment: microorganisms and bioremediation. Appl Microbiol Biotechnol 2016; 100: 2967-84.
40. Sun B and Zhang M: Analysis of the antibacterial effect of an Edwardsiellatarda Lux S inhibitor. Springer Plus 2016; 5(1): 1-6.
41. Grover N, Plaks JG, Summers SR, Chado GR, Schurr MJ and Kaar JL: Acylase‐containing polyurethane coatings with anti‐biofilm activity. Biotechnology and Bioengineering 2016; 113(12): 2535-43.
42. Liu W, Ran C, Liu Z, Gao Q, Xu S, Ringø E, Myklebust R, Gu Z and Zhou Z: Effects of dietary Lactobacillus plantarum and AHL lactonase on the control of Aeromonas hydrophila infection in tilapia. Microbiology Open 2016; 5(4): 687-99.
43. Ivanova K, Fernandes MM, Mendoza E, Tzanov T. Enzyme multilayer coatings inhibit Pseudomonas aeruginosa biofilm formation on urinary catheters. Applied Microbiology and Biotechnology 2015; 99(10): 4373-85.
44. Li L, Gu Z, Liu Z and Su L: The effect of reactive oxygen species regulation of expression of Bcl-2 and Bax in apoptosis of human umbilical vein endothelial cell induced by heat stress. Zhonghuawei Zhong Bing ji jiu yixue 2014; 26(7): 458-63.
45. Thomas S, Holland IB and Schmitt L: The type 1 secretion pathway the hemolysin system and beyond. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 2014; 1843(8): 1629-41.
46. Storz MP, Allegretta G, Kirsch B, Empting M and Hartmann RW: From in-vitro to in-cellulo: structure–activity relationship of (2-nitrophenyl) methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa. Organic & Biomolecular Chemistry 2014; 12(32): 6094-104.
47. Yadav MK, Park SW, Chae SW and Song JJ: Sinefungin, a natural nucleoside analogue of S-adenosylmethionine, inhibits Streptococcus pneumoniae biofilm growth. BioMed Research International 2014; 2014.
48. Weng LX, Yang YX, Zhang YQ and Wang LH: A new synthetic ligand that activates QscR and blocks antibiotic-tolerant biofilm formation in Pseudomonas aeruginosa. Applied Microbiology and Biotechnology 2014; 98(6): 2565-72.
49. Vinoj G, Vaseeharan B, Thomas S, Spiers AJ and Shanthi S: Quorum-quenching activity of the AHL-lactonase from Bacillus licheniformis DAHB1 inhibits Vibrio biofilm formation in-vitro and reduces shrimp intestinal colonisation and mortality. Marine Biotechnology 2014; 16(6): 707-15.
50. Halbedl S, Kratzer MC, Rahm K, Crosta N, Masters KS, Zippert J, Bräse S and Gradl D: Synthesis of novel inhibitors blocking Wntsignaling downstream of β-catenin. FEBS Letters 2013; 587(5): 522-7.
51. Takayama H, Jia ZJ, Kremer L, Bauer JO, Strohmann C, Ziegler S, Antonchick AP and Waldmann H: Discovery of Inhibitors of the Wnt and Hedgehog Signaling Pathways through the Catalytic Enantioselective Synthesis of an Iridoid‐Inspired Compound Collection. Angewandte Chemie International Edition 2013; 52(47): 12404-8.
52. Zhu J, Hixon MS, Globisch D, Kaufmann GF, Janda KD. Mechanistic insights into the LsrK kinase required for autoinducer-2 quorum sensing activation. Journal of the American Chemical Society 2013; 135(21): 7827-30.
53. Kumar S and Varela MF: Biochemistry of bacterial multidrug efflux pumps. International Journal of Molecular Sciences 2012; 13(4): 4484-95.
54. Chebotar IV, Mayanskiy AN, Konchakova ED, Lazareva AV and Chistyakova VP: Antibiotic resistance of biofilm bacteria. Klinicheskaya mikrobiologiyai antimikrobnayakhimioterapiya 2012; 14(1): 51-8.
55. Truchado P, Giménez-Bastida JA, Larrosa M, Castro-Ibáñez I, Espı́n JC, Tomás-Barberán FA, Garcı́a-Conesa MT antimikrobnayakhimioterapiya Allende A: Inhibition of quorum sensing (QS) in Yersinia enterocolitica by an orange extract rich in glycosylated flavanones. Journal of Agricultural and Food Chemistry 2012; 60(36): 8885-94.
56. Brackman G antimikrobnayakhimioterapiya Coenye T: Quorum sensing inhibitors as anti-biofilm agents. Current Pharmaceutical Design 2015; 21(1): 5-11.
57. Roy V, Adams BL antimikrobnayakhimioterapiya Bentley WE: Developing next generation antimicrobials by intercepting AI-2 mediated quorum sensing. Enzyme and Microbial Technology 2011; 49(2): 113-23.
58. Han X antimikrobnayakhimioterapiya Lu C: Biological activity and identification of a peptide inhibitor of LuxS from Streptococcus suis serotype 2. FEMS Microbiology Letters 2009; 294(1): 16-23.
59. Zang T, Lee BW, Cannon LM, Ritter KA, Dai S, Ren D, Wood TK antimikrobnayakhimioterapiya Zhou ZS: A naturally occurring brominated furanone covalently modifies and inactivates LuxS. Bioorganic & Medicinal Chemistry Letters 2009; 19(21): 6200-4.
60. Schramm VL, Gutierrez JA, Cordovano G, Basu I, Guha C, Belbin TJ, Evans GB, Tyler PC antimikrobnayakhimioterapiya Furneaux RH: Transition state analogues in quorum sensing and SAM recycling. In Nucleic acids Symposium Series 2004; 2008: 52-75. NIH Public Access
61. González JE antimikrobnayakhimioterapiya Keshavan ND: Messing with bacterial quorum sensing. Microbiology and Molecular Biology Reviews 2006; 70(4): 859-75.
62. Singh V, Evans GB, Lenz DH, Mason JM, Clinch K, Mee S, Painter GF, Tyler PC, Furneaux RH, Lee JE antimikrobnayakhimioterapiya Howell PL: Femtomolar transition state analogue inhibitors of 5′-methylthioadenosine/S-adenosyl homocysteine nucleosidase from Escherichia coli. Journal of Biological Chemistry 2005; 280(18): 18265-73.
63. Henke JM antimikrobnayakhimioterapiya Bassler BL: Bacterial social engagements. Trends in Cell Biology 2004; 14(11): 648-56.
64. Maseda H, Sawada I, Saito K, Uchiyama H, Nakae T antimikrobnayakhimioterapiya Nomura N: Enhancement of the mexAB-oprM efflux pump expression by a quorum-sensing autoinducer and its cancellation by a regulator, MexT, of the mexEF-oprN efflux pump operon in Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 2004; 48(4): 1320-8.
65. Dong YH, Wang LH, Xu JL, Zhang HB, Zhang XF antimikrobnayakhimioterapiya Zhang LH: Quenching quorum-sensing-dependent bacterial infection by an N-acyl homoserine lactonase. Nature 2001; 411(6839): 813-7.
    

    ---

    How to cite this article:

    Thakur S, Sharma R and Yadav R: A way of combating antimicrobial resistance through quorum sensing. Int J Pharm Sci & Res 2022; 13(10): 3833-40. doi: 10.13040/IJPSR.0975-8232.13(10).3833-40.

    ---

    All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.