Authors:
Hossein Saghi, Fateme Moradi, Razieh Mohseni, Amir Hossein Abadi, Ramezan Ali Ataee, Parnia Baban Zadeh, Maryam Meskini, and Davoud Esmaeili*
Affiliation(s):
Department of Microbiology, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
Dates:
Received: 05 June, 2015; Accepted: 09 July, 2015; Published: 10 July, 2015
*Corresponding author:
Davoud Esmaeili, Department of Microbiology, Baqiyatallah University of Medical Sciences, Tehran, IR Iran. Tel: +98-9124395884; Fax: +98-2177601533; Email: @
Citation:
Saghi H, Moradi F, Mohseni R, Abadi AH, Ataee RA, et al. (2015) Quorum Sensing in Bacterial Pathogenesis. Glob J Infect Dis Clin Res 1(1): 004-009. DOI: 10.17352/2455-5363.000002
Copyright:
© 2015 Saghi H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords:
Quorum sensing; Pathogenesis; AHL

Introduction: Quorum sensing (QS) in the word means a gathering or a fixed number of objectives and say the microbes sense of awareness of the presence of bacteria and their community is. Bacteria in social life, the greatest benefit from the competitive environment to get the genetic regulatory mechanisms they use.

Materials and Methods: This paper is a review article through library research and internet search sites, PubMed, Sid, Google Scholar keyword (Quorum sensing, AHL, pathogenesis) is collected in the years 2005 to 2014.

Results: Quorum sensing in bacteria (pathogens and non-pathogens) regulates cell activity in quickly adapting to changing environmental conditions for maintenance and survival of bacteria in the environment. Process that is regulated by Quorum sensing including biofilm formation, Conjugation, produce virulence factors, toxin production and escape from the immune system. In this paper, we investigate the existence QS in gram-negative and gram-negative bacteria and its role in the pathogenesis of some of the major virulence factors are discussed.

Conclusions: Increased prevalence of bacterial strains resistant to antimicrobial drugs is a big problem to find a new way to treat these infections is important. QS System to prevent damage to the opportunity to respond to the signal and prevent the bacteria express virulence factors follows. My hope is that by using antagonists and agonists can control so many dangerous diseases.

Introduction

Bacteria in the collective and social life for the greatest benefit of the competitive environment in case of genetic regulatory mechanisms of communication called Quorum sensing (QS) is used. Quorum literally means an assembly or a fixed number of each class of objects called QS means of microbes and their community is aware of the presence of bacteria. Quorum sensing in all bacteria (pathogenic and non-pathogenic) regulate cell activities in quickly adapting to changing environmental conditions and to maintain the survival of bacteria in the environment. Process that is regulated by Quorum sensing including biofilm formation, Conjugation, Sporulation, produce virulence factors, invasion and toxin production is [11. Stevens AM, Greenberg EP (1999) Cell-Cell Signaling in Bacteria (Eds Dunny GM, Winans SC) (ASM Press, Washington D.C,1999).-33. Basler BL (2002) Small talk: Cell-to-cell communication in bacteria. Cell 109: 421-424.].

In this paper, we investigate the QS positive and gram-negative bacteria and its role in the pathogenesis of some of the major virulence factors have been examined in the following factors in prokaryotes and eukaryotes suggests that these molecules parser. It is hoped that the use of antagonists and agonists can be used to control most dangerous infectious agents.

Quorum sensing History

In 1970, the first QS in bacteria Vibrio fischeri were observed. The researchers found that the Gram-negative bacterium that lives in a free-living in the seas and oceans. The low number does not produce luciferase but when the luminous organs of fish or marine bacteria holes cephalopods (Euprymna scolopes) into the holes where the organs of reproduction is and then increase the number of bacteria, QS active and causes the activation of luciferase gene and luminance phenomenon occurs.

Signaling mechanisms in prokaryotes

Prokaryotes for messaging cell to the different mechanisms of pheromone-like peptide-modified peptides, QS and intracellular kinases are activated. The Table 1 below shows the mechanisms of bacterial signaling and its role in the processes shown in [55. Zhang RG, Pappas T, Brace JL, Miller PC, Oulmassov T, et al. (2002) Structure of a bacterial quorum-sensing transcription factor completed with pheromone and DNA. Nature 417: 971-974.].

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    Table 1:

    Community bacteria together with different mechanisms of cell-to-cell signaling.

As can be seen in its response induced peptide pheromone QS and a large number of bacteria involved.

Micsococos gezantuse, a Gram-negative bacterium found in soil, if bacteria grow again in appropriate circumstances is removed layers and bacteria will multiply. The stages of differentiation by extracellular signals to produce small peptides are the KD17 forms. Bacillus subtilis, two different peptide which is capable of being used for transformation and spore formation it is necessary [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.,33. Basler BL (2002) Small talk: Cell-to-cell communication in bacteria. Cell 109: 421-424.].

QS in Gram-negative bacteria

As noted above QS concept first discussed in gram-negative bacteria Pathogenic and non-pathogenic. Gram-negative bacteria or molecules that self-discharge phenomena such as biofilm formation, virulence, move, produce antibiotics, luminance and plasmid transfer can be involved. QS in the pathogenesis of bacteria such as Pseudomonas aeruginosa, Burkholderia Cepacia, Salmonella typhimurium, Yersinia enterocolitica, Escherichia coli, Vibrio cholera and Serratia species [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.,33. Basler BL (2002) Small talk: Cell-to-cell communication in bacteria. Cell 109: 421-424.].

QS in Gram-positive bacteria

In Gram-positive bacteria such as gram-negative bacteria, QS infection, antibiotic production, biofilm, and so is the role and structure of QS molecules in Gram-positive bacteria differ from gram-negative bacteria (Figure 1).

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    Figure 1:

    Different types of buildings are auto inductor (AI) in positive and Gram-negative bacteria.

Gram positive more molecules of peptide Octa or Hepta who called pheromone involved in transmitting messages. These molecules that are hydrophobic low molecular weight (5×10-11m) and at least two molecules per cell of these peptides with biological activity there. Receptor agonist study suggests that these molecules messaging system similar to cytokine signaling in eukaryotic .QS in various gram-positive bacteria such as Staphylococcus aurous, Bacillus and Actioiomycetes been observed and studied [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.,33. Basler BL (2002) Small talk: Cell-to-cell communication in bacteria. Cell 109: 421-424.].

Types of QS molecules

Unless, of bacteria with similar auto inductor communicate with each other, and because any bacteria to induce the same way it responds to various types of inductor in bacteria is discussed. The most important signal to the cell-cell communication in bacteria was discovered for the first time AHL, which is only produced in gram-negative bacteria and a lactone ring and side chain in its structure (Figure 1). Different bacteria produce different AHL molecules that differ in the side chain. It should be noted that the side chain of the lactone ring QS activity is essential for any changes (create unsaturated bonds or the formation of large groups), auto inductor activity is affected. For example, if the lactone rings of Vibrio fisher Hemoserin be used instead of homocysteine-induced decreases its activity [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.,66. Fuqua C, Parsek MR, and Greenberg EP (2001) Regulation of gene expression by cell-to-cell communication: Acyl-homoserine lactone quorum sensing. Annu Rev Genet 35: 439-468.-88. De Kievit TR, Iglewski BH (2000) Bacterial quorum sensing in pathogenic relationships. Infect Immune 68: 4839-4849.].

Gram-negative bacteria as signal molecules in the cell-to-cell communication used are: acyl Hemoserin lactone (AHL), Thiolactone ring (AIP), hydroxyl palmitic acid methyl ester (PAME), Foranozil methyl borate (AI-2) and Dodicanoiec acid methyl (DSF) [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.,33. Basler BL (2002) Small talk: Cell-to-cell communication in bacteria. Cell 109: 421-424.].

It should be noted that QS is not only restricted to prokaryotes and eukaryotes, particularly fungi are produced and these molecules are involved in their pathogenesis. For example, Candida albicans with Foranozoeik acid (FA), has become a form of yeast to the mycelium form has an important role in the pathogenesis of controls [22. Miller MB, Basler BL (2001) Quorum sensing in bacteria. Annu Rev Microbial 55: 165-199.].

Molecular mechanisms messaging QS

QS to convey a message to the protein ProI (auto inductor) and ProR (transcription factor receptor) (Figure 2). As can be seen messaging system is controlled by the genes involved in virulence genes i and r is controlled by a protein complex RI. The complex, RI, ProR and ProI genes encoding transcription regulatory feedback mechanism to enable or disable when the system was too much ProI in connection ProR transcription factor is the increase in the production of AI [99. Eberhard A, Burlingame AL, Eberhard C, Kenyon GL, Nealson KH, et al. (1981) Structural identification of auto inducer of Photo bacterium fischeri luciferase. Biochemistry 20: 2444-2449.-1313. Yao Y, Martinez-Yamout MA, Dickerson TJ, Brogan AP, Wright PE, et al. (2006) Structure of the Escherichia coli Quorum Sensing Protein SdiA: Activation of the Folding Switch by Acyl Homoserine Lactones. J Mol Biol 355: 262-273.].

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    Figure 2:

    Molecules involved in signaling by QS.


QS in Vibrio fisher

Cephalopods are illuminated when the bacteria enter the tissues where it accumulates at a concentration of 1011 ml AHL produces the molecule activates luciferase gene produces light at night. The bacterial Lux I Homologous ProI and LuxR Homologous is ProR. When these two proteins were formed together in addition to the control of RI, LuxI and LuxR of the genes involved in the production of light (Figure 2), [44. Nealson KH, Platt T, Hastings JW (1970) Cellular control of the synthesis and activity of the bacterial luminescent system. J Bacterial 104: 313-322.,1010. Engebrecht J, Silverman M (1984) Identification of genes and gene products necessary for bacterial bioluminescence. Proc Natl Acad Sci USA 81: 4154-4158.,1111. Kim MH, Choi WC, Kang HO, Lee JS, Kang BS, et al. (2005) The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase. Biochemistry 102: 17606-17611.].

QS in Vibrio cholera

Vibrio cholerae causes cholera is to produce exotoxins. It consists of 20 genes involved in the pathogenicity of the bacteria has a Regolon the production and secretion of toxins and genes required for survival in host cells. These genes regulate transcription Regolon toxT, tcpP / I, toxR a cascade controlled. The adjustment to external factors such as temperature, pH, osmotic pressure, and so respond. It is now clear that QS is involved in the regulation of these genes (Figure 3) [1414. Miguel C, Andrea H, Paul Williams, Debra Milton (2002) Quorum sensing in Vibrio cholerae. Nature genetics 32: 217-218.].

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    Figure 3:

    The role of QS in the Vibrio cholera in the intestine.


QS in Pseudomonas aeruginosa

Pseudomonas aeruginosa a gram-negative bacillus that due to the high resistance of biofilms to antibiotics, variation in the nature and cause severe nosocomial infections in the hospital. Studies show that the bacterium is an opportunistic pathogen of more than 600 genes is controlled by QS. The QS and biofilm formation in a high drug resistance in bacteria is essential. If using QS and its antagonists, biofilm inhibition may be a chronic infection and drug resistance in the bacteria solution of the above.

Pseudomonas aeruginosa QS system has two named RhlR / I and LasR / I is.

System LasR / I, Regolon rhl pathogenicity genes toxA, apr, lasA, lasB controls and systems RhlR / I, production of elastase (IL-2 has a breaking strength) controls. The bacteria with the help of the system, the ability to survive and multiply within cells are found (Figure 4), [1616. Preston MJ, Seed PC, Toder DS, Iglewski BH, Ohman DE, et al. (1997) Contribution of proteases and LasR to the virulence of Pseudomonas aeruginosa during corneal infections. Infect immune 65: 3086-3090.-1818. Wu H, Song Z, Givskov M, Doring G, Worlitzsh D, et al. (2001) Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection. Microbial 147: 1105-1113.].

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    Figure 4:

    Activity of Pseudomonas aeruginosa QS.


QS in Staphylococcus aurous

These proteins are produced in different stages of growth and may be controlled by QS early stage of infection has spread to nearby tissues show. General accessory gene regulator agr operon has two important and one of the operon, a RNA molecule that encodes a unique name RNAIII increased secretory protein expression and decreased expression of surface proteins. In contrast to the RNAIII, a promoter region of a gene responsible for the expression of RNAII gene called four agr BDCA that these genes are essential for the expression of RNAIII optimized. AgrD and agrB genes encoded a small peptide (QS). The production of these molecules was dependent on cell density and RNAII and RNAIII helps control gene expression (Figure 5), [2020. Gov Y, Borovok I, Korem M, Singh VK, Jayaswal RK, et al. (2004) Quorum sensing in Staphylococci is regulated via phosphorylation of three conserved histidine residues. J Biol Chem 279:14665-14672.-2222. Yang G, Cheng HC, Liu C, Xue YN, Gao YP, et al. (2003) Inhibition of Staphylococcus aurous pathogenesis in vitro and in vivo by RAP binding peptides. Peptides 24: 1823–1828.].

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    Figure 5:

    QS activity of S. aurous.


Analysis of molecules Q.S

Studies show that prokaryotes and eukaryotes great (especially mammals) with the production of enzymes, the QS molecules are decomposed, so we can help these enzymes, inhibit the microbial pathogenicity. In bacteria such as Bacillus and Klebsiella pneumonia, Pseudomonas aeruginosa AHL-degrading enzymes produced [2727. Hentzer M, Riedel K, Rasmussen TB, Heydorn A, Andersen JB, et al (2002) Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furan one compound. Microbial 148: 87-102.-2929. Suga H, Smith KM (2003) Molecular mechanisms of bacterial quorum sensing as a new drug target. Current Opinion in Chemical Biology 7: 586–591.]. One of the enzymes in bacteria has been studied AHL - Quorum-Quenching Laktonaz that the enzyme activity and aiiA or attM coded by genes. AiiA gene in Bacillus cereus strains uw85 code and makes the QS in bacteria inhibited Chromobacterium violaceum. Enzymes produced by different genes in Bacillus together have 90% similarity [3030. Dong YH, Xu JL, Li XZ, Zhang LH (2000) AiiA a novel enzyme inactivates acyl-homoserine lactone quorum-sensing signal and attenuates the virulence of Erwinia carotovora. Proc Natl Acad Sci U S A 97: 3526-3531.,3131. Dong YH, Zhang LH (2005) Quorum Sensing and Quorum-Quenching Enzymes. The Journal of Microbiology 43: 101-109.]. The human enzyme produced by epithelial cells of the airways Kh3- o-C12-HSL, C6-HSL (but not C4-HSL)breaks that some researchers believe that this is due to the production of enzymes Para-oxygenase (by only PoN3) and PoN1, break the lactone ring [3131. Dong YH, Zhang LH (2005) Quorum Sensing and Quorum-Quenching Enzymes. The Journal of Microbiology 43: 101-109.].

QS Antagonists

The control of pathogenic bacteria, consider different ways. One of them, the microbes is QS control. To this end, researchers from a variety of natural and synthetic antagonists have been used to control QS. Auto inductor a natural antagonist, Foranoz is produced by a type of algae called Delissea pulchra and is used to prevent the bacteria.

This natural compound sterile barrier SwrR-C- reactive and preventive action LuxR-3-Oxo-C6- HSL and CarR-3-oxo-C6- HSL in Vibrio fisher but on LasR-oxo- C12- HSL Pseudomonas aeruginosa is less effective. Some synthetic antagonists due to changes in the (3- Oxo- C12-D10) Foranoz ring chain length fatty acids and prevents biofilm formation in Pseudomonas aeruginosa is able to reduce the number of pathogens.

The antagonists are likely “to avoid being LasR dimer that is essential to avoid duplication and transcription activation are pathogens [3131. Dong YH, Zhang LH (2005) Quorum Sensing and Quorum-Quenching Enzymes. The Journal of Microbiology 43: 101-109.,3232. Olsen JA, Severinsen R, Rasmussen TB, Hentzer M, Givskov M, (2002) Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers.Bioorg Med Chem Lett 12: 325-328.].

Conclusion

Increased prevalence of bacterial strains sustained antimicrobial drug and multi-drug resistant strains is a huge problem to find a new way to treat life-threatening bacterial infections require. The QS system is an opportunity to prevent the destruction of bacteria to respond to signals and inhibit the expression of virulence factors cause. The AI is designed drugs inhibiting the biosynthesis process. The therapeutic approach in addition to inhibiting the production of virulence factors, the intervention of differentiated biofilms, and bacterial sensitivity to antibiotics has increased [3333. de Kievit TR, Iglewski BH (2000) Bacterial Quorum sensing in pathogenic relationship. In fect Immune 4839-4849.]. QS, a method by which bacteria communicate with each other and in this way you can tune into their genomic expression patterns in the face of environmental change. QS In all Gram-negative bacteria is dependent on cell density and bacteria, Gram-positive bacteria and AHL molecules such as small peptides are called pheromones. These molecules are caused by bacteria that grow out or not growth, toxin producing or not producing. Staphylococcus aurous in the stationary phase and Vibrio cholera toxin is produced in the logarithmic phase. Mycobacterium tuberculosis in the logarithmic growth phase, which are invasive procedures regulated by QS. Research shows that prokaryotes and large eukaryotes (especially mammals) with the production of enzymes, the QS molecules are decomposed, so today antagonists and agonists of reducing pathogenicity of infectious agents such as Pseudomonas aeruginosa, Vibrio cholera and staphylococcus aurous [1111. Kim MH, Choi WC, Kang HO, Lee JS, Kang BS, et al. (2005) The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase. Biochemistry 102: 17606-17611.,2828. Smith KM, Bu Y, Suga H (2003) Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic auto inducer analogs. Chem Biol 10: 81-89.]. Also today with restrictive QS, anti-bacterial drugs produced in the control of infections in medical, agricultural and industrial applications [2828. Smith KM, Bu Y, Suga H (2003) Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic auto inducer analogs. Chem Biol 10: 81-89.,2929. Suga H, Smith KM (2003) Molecular mechanisms of bacterial quorum sensing as a new drug target. Current Opinion in Chemical Biology 7: 586–591.].

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