Population level virulence in polymicrobial communities associated with chronic disease

Abstract

Renewed studies of chronic infection have shifted the focus from single pathogens to multi-microbial communities as culture-independent techniques reveal complex consortia of microbes associated with chronic disease. Despite a general acceptance that some chronic diseases are caused by mixed microbial communities, areas of research exploring community interactions as they relate to the alteration of virulence are still in the early stages. Members of the NIH Human Microbiome Project have been actively characterizing the microbial communities of the skin, nasal, oral, gastrointestinal, and urogenital cavities of healthy adults. Concomitantly, several independent studies have begun to characterize the oral, nasal, sinus, upper and lower respiratory microbiomes in healthy and diseased human tissue. The interactions among the members of these polymicrobial communities have not been thoroughly explored and it is clear there is a need to identify the functional interactions that drive population-level virulence if new therapeutic approaches to chronic disease are to be developed. For example, multiple studies have examined the role of quorum sensing (QS) in microbial virulence, and QS antagonists are being developed and tested as novel therapeutics. Other potential targets include the Gram-negative type III signaling system (T3SS), type IV pili, and two component regulatory systems (TCRS). Initial results from these studies indicate limited efficacy in vivo, further suggesting that the interactions in a heterogeneous community are complex and poorly understood. If progress is to be made in the development of more effective treatments for chronic diseases, a better understanding of the composition and functional interactions that occur within multi-microbial communities must be developed.

Keywords

polymicrobial / chronic infection / quorum sensing / therapeutics

References

[1] Anzaudo M M, Busquets N P, Ronchi S, Mayoral C (2005). Isolated pathogen microorganisms in respiratory samples from children with cystic fibrosis. Rev Argent Microbiol, 37(3): 129–134

[2] Armbruster C E, Hong W, Pang B, Weimer K E, Juneau R A, Turner J, Swords W E (2010). Indirect pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in polymicrobial otitis media occurs via interspecies quorum signaling. MBio, 1(3): e00102-10–e00102-19

[3] Arthur M, Molinas C, Courvalin P (1992). The VanS-VanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacteriol, 174(8): 2582–2591

[4] Baddour L M, Christensen G D (1987). Prosthetic valve endocarditis due to small-colony staphylococcal variants. Rev Infect Dis, 9(6): 1168–1174

[5] Bader M S (2008). Diabetic foot infection. Am Fam Physician, 78(1): 71–79

[6] Bakaletz L O (2010). Immunopathogenesis of polymicrobial otitis media. J Leukoc Biol, 87(2): 213–22

[7] Bala A, Kumar R, Harjai K(2011). Inhibition of quorum sensing in Pseudomonas aeruginosaby azithromycin and its effectiveness in urinary tract infections. J Med Microbiol, 60(Pt 3): 300–306

[8] Bassler B L (1999). How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr Opin Microbiol, 2(6): 582–587

[9] Bassler B L, Wright M, Silverman M R (1994). Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol, 13(2): 273–286

[10] Bjarnsholt T, Givskov M (2007). Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens. Philos Trans R Soc Lond B Biol Sci, 362(1483): 1213–22

[11] Bjarnsholt T, Jensen P O, Jakobsen T H, Phipps R, Nielsen A K, Rybtke M T, Tolker-Nielsen T, Givskov M, Høiby N, Ciofu O, the Scandinavian Cystic Fibrosis Study Consortium (2010). Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients. PLoS One, 5(4): e10115

[12] Boles B R , Thoendel M, Singh P K(2005). Genetic variation in biofilms and the insurance effects of diversity. Microbiology, 151(Pt 9: 2816–2818

[13] Brown S M (2010). Multiple strains of non-tuberculous mycobacteria in a patient with cystic fibrosis. J R Soc Med, 103(Suppl 1): 34–43

[14] Burmolle M, Thomsen T R, Fazli M, Dige I, Christensen L, Homoe P, Tvede M, Nyvad B, Tolker-Nielsen T, Givskov M, Moser C, Kirketerp-Moller K, Johansen H K , Hoiby N, Jensen P O, Sorensen S J, Bjarnsholt T (2010). Biofilms in chronic infections — a matter of opportunity — monospecies biofilms in multispecies infections. FEMS Immunol Med Microbiol, 59(3), 324–336

[15] Burns J L, Emerson J, Stapp J R, Yim D L, Krzewinski J, Louden L, Ramsey B W, Clausen C R (1998). Microbiology of sputum from patients at cystic fibrosis centers in the United States. Clin Infect Dis, 27(1): 158–163

[16] Chan J, Hadley J (2001). The microbiology of chronic rhinosinusitis: results of a community surveillance study. Ear Nose Throat J, 80(3): 143–145

[17] Charlson E S, Chen J, Custers-Allen R, Bittinger K, Li H, Sinha R, Hwang J, Bushman F D, Collman R G (2010). Disordered microbial communities in the upper respiratory tract of cigarette smokers. PLoS ONE, 5(12): e15216

[18] Chen P B, Davern L B, Katz J, Eldridge J H, Michalek S M (1996). Host responses induced by co-infection with Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans in a murine model. Oral Microbiol Immunol, 11(4): 274–281

[19] Cherry D K, Woodwell D A (2002). National Ambulatory Medical Care Survey: 2000 summary. Adv Data, 328: 1–32

[20] Deng D M, Liu M J, ten Cate J M, Crielaard W (2007). The VicRK system of Streptococcus mutans responds to oxidative stress. J Dent Res, 86(7): 606–610

[21] Dewhirst F E, Chen T, Izard J, Paster B J, Tanner A C, Yu W H, Lakshmanan A, Wade W G (2010). The human oral microbiome. J Bacteriol, 192(19): 5002–5017

[22] Duque C, Stipp R N, Wang B, Smith D J, Hofling J F, Kuramitsu H K, Duncan M J, Mattos-Graner R O (2011). Downregulation of GbpB, a component of the VicRK regulon, affects biofilm formation and cell surface characteristics of Streptococcus mutans. Infect Immun, 79(2): 786–796

[23] Ebersole J L, Feuille F, Kesavalu L, Holt S C (1997). Host modulation of tissue destruction caused by periodontopathogens: effects on a mixed microbial infection composed of Porphyromonas gingivalis and Fusobacterium nucleatum. Microb Pathog, 23(1): 23–32

[24] Ehrlich G D, Ahmed A, Earl J, Hiller N L, Costerton J W, Stoodley P, Post J C, Demeo P, Hu F Z (2010). The distributed genome hypothesis as a rubric for understanding evolution in situ during chronic bacterial biofilm infectious processes. FEMS Immunol Med Microbiol, 59(3): 269–279

[25] Ehrlich G D, Hiller N L, Hu F Z (2008). What makes pathogens pathogenic. Genome Biol, 9(6): 225

[26] Ehrlich G D, Hu F Z, Shen K, Stoodley P, Post J C (2005). Bacterial plurality as a general mechanism driving persistence in chronic infections. Clin Orthop Relat Res, (437):20–24

[27] Evers S, Courvalin P (1996). Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR (B) two-component regulatory system in Enterococcus faecalis V583. J Bacteriol, 178(5): 1302–1309

[28] Falleiros de Padua R A, Norman Negri M F, Svidzinski A E, Nakamura C V, Svidzinski T I (2008). Adherence of Pseudomonas aeruginosa and Candida albicans to urinary catheters. Rev Iberoam Micol, 25(3): 173–175

[29] Feuille F, Ebersole J L, Kesavalu L, Stepfen M J, Holt S C (1996). Mixed infection with Porphyromonas gingivalis and Fusobacterium nucleatum in a murine lesion model: potential synergistic effects on virulence. Infect Immun, 64(6): 2094–2100

[30] Foreman A, Psaltis A J, Tan L W, Wormald P J (2009). Characterization of bacterial and fungal biofilms in chronic rhinosinusitis. Am J Rhinol Allergy, 23(6): 556–561

[31] Foreman A, Wormald P J (2010). Different biofilms, different disease? A clinical outcomes study. Laryngoscope, 120(8): 1701–1706

[32] Galperin M Y(2006). Structural classification of bacterial response regulators: diversity of output domains and domain combinations. J Bacteriol, 188(12): 4169–4182

[33] Geske G D, O’Neill J C, Blackwell H E (2007). N-phenylacetanoyl-L-homoserine lactones can strongly antagonize or superagonize quorum sensing in Vibrio fischeri. ACS Chem Biol, 2(5): 315–319

[34] Geske G D, O’Neill J C, Miller D M, Mattmann M E, Blackwell H E (2007). Modulation of bacterial quorum sensing with synthetic ligands: systematic evaluation of N-acylated homoserine lactones in multiple species and new insights into their mechanisms of action. J Am Chem Soc, 129(44): 13613–13625

[35] Gotoh Y, Doi A, Furuta E, Dubrac S, Ishizaki Y, Okada M, Igarashi M, Misawa N, Yoshikawa H, Okajima T, Msadek T, Utsumi R(2010). Novel antibacterial compounds specifically targeting the essential WalR response regulator. J Antibiot (Tokyo), 63(3): 127–134

[36] Guggenheim B, Gmur R, Galicia J C, Stathopoulou P G, Benakanakere M R, Meier A, Thurnheer T, Kinane D F(2009). In vitro modeling of host-parasite interactions: the ‘subgingival’ biofilm challenge of primary human epithelial cells. BMC Microbiol, 9: 280

[37] Hall-Stoodley L, Hu F Z, Gieseke A, Nistico L, Nguyen D, Hayes J, Forbes M, Greenberg D P, Dice B, Burrows A, Wackym P A, Stoodley P, Post J C, Ehrlich G D, Kerschner J E(2006). Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media. JAMA, 296(2): 202–211

[38] Healy D Y, Leid J G, Sanderson A R, Hunsaker D H(2008). Biofilms with fungi in chronic rhinosinusitis. Otolaryngol Head Neck Surg, 138(5): 641–647

[39] Hemady R K (1995). Microbial keratitis in patients infected with the human immunodeficiency virus. Ophthalmology, 102(7): 1026–1030

[40] Hentzer M, Eberl L, Nielsen J, Givskov M(2003). Quorum sensing: a novel target for the treatment of biofilm infections. BioDrugs, 17(4): 241–250

[41] Hentzer M, Wu H, Andersen J B, Riedel K, Rasmussen T B, Bagge N, Kumar N, Schembri M A, Song Z, Kristoffersen P, Manefield M, Costerton J W, Molin S, Eberl L, Steinberg P, Kjelleberg S, Høiby N, Givskov M (2003). Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J, 22(15): 3803–3815

[42] Hermann C, Hermann J, Munzel U, Røchel R (1999). Bacterial flora accompanying Candida yeasts in clinical specimens. Mycoses, 42(11-12): 619–627

[43] Higgins D A, Pomianek M E, Kraml C M, Taylor R K, Semmelhack M F, Bassler B L(2007). The major Vibrio cholerae autoinducer and its role in virulence factor production. Nature, 450(7171): 883–886

[44] HoffmanL R, Deziel E, D'Argenio D A, Lepine F, Emerson J, McNamara S, Gibson R L, Ramsey B W, Miller S I(2006). Selection for Staphylococcus aureus small-colony variants due to growth in the presence of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A, 103(52): 19890–19895

[45] Hogan D A, Kolter R (2002). Pseudomonas-Candida interactions: an ecological role for virulence factors. Science, 296(5576): 2229–22232

[46] Hoiby N (1974). Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis. Acta Pathol Microbiol Scand B Microbiol Immunol, 82(4): 541–550

[47] Høiby N, Ciofu O, Bjarnsholt T (2010). Pseudomonas aeruginosa biofilms in cystic fibrosis. Future Microbiol, 5(11): 1663–1674

[48] Holcombe L J, McAlester G, Munro C A, Enjalbert B, Brown A J, Gow N A, Ding C, Butle G R, O’Gara F, Morrissey J P(2010). Pseudomonas aeruginosa secreted factors impair biofilm development in Candida albicans . Microbiology, 156(Pt 5): 1476–1486

[49] Hong H J, Hutchings M I, Buttner M J, the Biotechnology and Biological Sciences Research Council, U K (2008). Vancomycin resistance VanS/VanR two-component systems. Adv Exp Med Biol, 631: 200–213

[50] Hu F Z, Ehrlich G D (2008). Population-level virulence factors amongst pathogenic bacteria: relation to infection outcome. Future Microbiol, 3(1): 31–42

[51] Ito R, Ishihara K, Shoji M, Nakayama K, Okuda K (2010). Hemagglutinin/adhesin domains of Porphyromonas gingivalis play key roles in coaggregation with Treponema denticola. FEMS Immunol Med Microbiol, 60(3): 251–260

[52] Jakubovics N S, Kolenbrander P E(2010). The road to ruin: the formation of disease-associated oral biofilms. Oral Dis, 16(8): 729–739

[53] Jenkinson H F, Lamont R J(2005). Oral microbial communities in sickness and in health. Trends Microbiol, 13(12): 589–595

[54] Jesaitis A J, Franklin M J, Berglund D, Sasaki M, Lord C I, Bleazard J B, Duffy J E, Beyenal H, Lewandowski Z (2003). Compromised host defense on Pseudomonas aeruginosa biofilms: characterization of neutrophil and biofilm interactions. J Immunol, 171(8): 4329–4339

[55] Jones M B, Peterson S N, Benn R, Braisted J C, Jarrahi B, Shatzkes K, Ren D, Wood T K, Blaser M J(2010). Role of luxS in Bacillus anthracis growth and virulence factor expression. Virulence, 1(2): 72–83

[56] Kahl B, Herrmann M, Everding A S, Koch H G, Becker K, Harms E, Proctor R A, Peters G (1998). Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J Infect Dis, 177(4): 1023–1029

[57] Keren I, Kaldalu N, Spoering A, Wang Y, Lewis K(2004a). Persister cells and tolerance to antimicrobials. FEMS Microbiol Lett, 230(1): 13–18

[58] Keren I, Shah D, Spoering A, Kaldalu N, Lewis K (2004b). Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol, 186(24): 8172–8180

[59] Kesavalu L, Holt S C, Ebersole J L (1998). Virulence of a polymicrobic complex, Treponema denticola and Porphyromonas gingivalis, in a murine model. Oral Microbiol Immunol, 13(6): 373–377

[60] Klinger J D, Thomassen M J(1985). Occurrence and antimicrobial susceptibility of Gram-negative nonfermentative bacilli in cystic fibrosis patients. Diagn Microbiol Infect Dis, 3(2): 149–158

[61] Kolenbrander P E(2000). Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol, 54: 413–437

[62] Kolenbrander P E, Andersen R N, Blehert D S, Egland P G, Foster J S, Palmer R J Jr(2002). Communication among oral bacteria. Microbiol Mol Biol Rev, 66(3): 486–505

[63] Kolenbrander P E, Palmer R J Jr, Rickard A H, Jakubovics N S, Chalmers N I, Diaz P I(2006). Bacterial interactions and successions during plaque development. Periodontol 2000, 42: 47–79

[64] Krishnamurthy A, McGrath J, Cripps A W, Kyd J M (2009). The incidence of Streptococcus pneumoniae otitis media is affected by the polymicrobial environment particularly Moraxella catarrhalis in a mouse nasal colonisation model. Microbes Infect, 11(5): 545–553

[65] Lambiase A, Catania M R, Del Pezzo M, Rossano F, Terlizzi V, Sepe A, Raia V (2011). Achromobacter xylosoxidans respiratory tract infection in cystic fibrosis patients. Eur J Clin Microbiol Infect Dis,

[66] Lanza D C, Kennedy D W(1997). Adult rhinosinusitis defined. Otolaryngol Head Neck Surg, 117(Suppl 3): 1–7

[67] Lattar S M, Tuchscherr L P, Caccuri R L, Centron D, Becker K, Alonso C A, Barberis C, Miranda G, Buzzola F R, von Eiff C, Sordelli D O(2009). Capsule expression and genotypic differences among Staphylococcus aureus isolates from patients with chronic or acute osteomyelitis. Infect Immun, 77(5): 1968–1975

[68] Lee B, Haagensen J A, Ciofu O, Andersen J B, Hoiby N, Molin S(2005). Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis. J Clin Microbiol, 43(10): 5247–5255

[69] Leid J G, Costerton J W, Shirtliff M E, Gilmore M S, Engelbert M (2002). Immunology of Staphylococcal biofilm infections in the eye: new tools to study biofilm endophthalmitis. DNA Cell Biol, 21(5-6): 405–413

[70] Leid J G, Kerr M, Selgado C, Johnson C, Moreno G, Smith A, Shirtliff M E, O'Toole G A,Cope E K(2009). Flagellar-mediated biofilm defense mechanisms of Pseudomonas aeruginosa against host derived lactoferrin. Infect Immun, 77(10): 4559–4566

[71] Leid J G, Willson C J, Shirtliff M E, Hassett D J, Parsek M R,Jeffers A K(2005). The exopolysaccharide alginate protects Pseudomonas aeruginosa biofilm bacteria from IFN-gamma-mediated macrophage killing. J Immunol, 175(11): 7512–7518

[72] Li J, Helmerhorst E J, Leone C W, Troxler R F, Yaskell T, Haffajee A D, Socransky S S,Oppenheim F G(2004). Identification of early microbial colonizers in human dental biofilm. J Appl Microbiol, 97(6): 1311–1318

[73] Li M, Villaruz A E, Vadyvaloo V, Sturdevant D E,Otto M (2008). AI-2-dependent gene regulation in Staphylococcus epidermidis . BMC Microbiol, 8: 4

[74] Ly N,McCaig L F(2002). National Hospital Ambulatory Medical Care Survey: 2000 outpatient department summary. Adv Data, (327): 1–27

[75] Maeda S, Ito M, Ando T, Ishimoto Y, Fujisawa Y, Takahashi H, Matsuda A, Sawamura A, Kato S(2006). Horizontal transfer of nonconjugative plasmids in a colony biofilm of Escherichia coli. FEMS Microbiol Lett, 255(1): 115–120

[76] Moore J E, Reid A, Millar B C, Jiru X, Mccaughan J, Goldsmith C E, Collins J, Murphy P G, Elborn J S (2002). Pandoraea apista isolated from a patient with cystic fibrosis: problems associated with laboratory identification. Br J Biomed Sci, 59(3): 164–166

[77] Nadel D M, Lanza D C, Kennedy D W (1999). Endoscopically guided sinus cultures in normal subjects. Am J Rhinol, 13(2): 87–90

[78] Nyvad B, Kilian M (1987). Microbiology of the early colonization of human enamel and root surfaces in vivo. Scand J Dent Res, 95(5): 369–380

[79] Palmer R J Jr, Gordon S M, Cisar J O, Kolenbrander P E (2003). Coaggregation-mediated interactions of streptococci and actinomyces detected in initial human dental plaque. J Bacteriol, 185(11): 3400–3409

[80] Palmer R J Jr, Kazmerzak K, Hansen M C, Kolenbrander P E (2001). Mutualism versus independence: strategies of mixed-species oral biofilms in vitro using saliva as the sole nutrient source. Infect Immun, 69(9): 5794–5804

[81] Park J E, Yung R, Stefanowicz D, Shumansky K, Akhabir L, Durie P R, Corey M, Zielenski J, Dorfman R, Daley D, Sandford A J(2011). Cystic fibrosis modifier genes related to Pseudomonas aeruginosa infection. Genes Immun,

[82] Periasamy S, Kolenbrander P E (2009). Mutualistic biofilm communities develop with Porphyromonas gingivalis and initial, early, and late colonizers of enamel. J Bacteriol, 191(22): 6804–6411

[83] Perloff J R, Palmer J N (2004). Evidence of bacterial biofilms on frontal recess stents in patients with chronic rhinosinusitis. Am J Rhinol, 18(6): 377–380

[84] Peters B M, Jabra-Rizk M A, Scheper M A, Leid J G, Costerton J W, Shirtliff M E(2010). Microbial interactions and differential protein expre ssion in Staphylococcus aureus-Candida albicans dual-species biofilms. FEMS Immunol Med Microbiol, 59(3): 493–503

[85] Prince A A, Steiger J D, Khalid A N, Dogrhamji L, Reger C, Eau Claire S, Chiu A G, Kennedy D W, Palmer J N, Cohen N A (2008). Prevalence of biofilm-forming bacteria in chronic rhinosinusitis. Am J Rhinol, 22(3): 239–245

[86] Proctor R A, Von Eiff C, Kahl B C, Becker K, McNamara P, Herrmann M,Peters G(2006). Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol, 4(4): 295–305

[87] Ramsey M M, Whiteley M(2009). Polymicrobial interactions stimulate resistance to host innate immunity through metabolite perception. Proc Natl Acad Sci U S A, 106(5): 1578–1583

[88] Rickard A H, Palmer R J Jr, Blehert D S, Campagna S R, Semmelhack M F, Egland P G, Bassler B L,Kolenbrander P E(2006). Autoinducer 2: a concentration-dependent signal for mutualistic bacterial biofilm growth. Mol Microbiol, 60(6): 1446–1456

[89] Roberts M E, Stewart P S (2004). Modeling antibiotic tolerance in biofilms by accounting for nutrient limitation. Antimicrob Agents Chemother, 48(1): 48–52

[90] Rolauffs B, Bernhardt T M, von Eiff C, Hart M L, Bettin D (2002). Osteopetrosis, femoral fracture, and chronic osteomyelitis caused by Staphylococcus aureus small colony variants (SCV) treated by girdlestone resection—6-year follow-up. Arch Orthop Trauma Surg, 122(9-10): 547–550

[91] Romano J D,Kolter R(2005). Pseudomonas-Saccharomyces interactions: influence of fungal metabolism on bacterial physiology and survival. J Bacteriol, 187(3): 940–948

[92] Ryan R P,Dow J M(2008). Diffusible signals and interspecies communication in bacteria. Microbiology, 154(7): 1845–1858

[93] Sanderson A R, Leid J G, Hunsaker D(2006). Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis. Laryngoscope, 116(7): 1121–1126

[94] Schauder S, Shokat K, Surette M G, Bassler B L(2001). The LuxS family of bacterial autoinducers: biosynthesis of a novel quorum-sensing signal molecule. Mol Microbiol, 41(2): 463–476

[95] Shirtliff M E, Peters B M, Jabra-Rizk M A(2009). Cross-kingdom interactions: Candida albicans and bacteria. FEMS Microbiol Lett, 299(1): 1–8

[96] Soni K A, Lu L, Jesudhasan P R, Hume M E,Pillai S D(2008). Influence of autoinducer-2 (AI-2) and beef sample extracts on E. coli O157:H7 survival and gene expression of virulence genes yadK and hhA. J Food Sci, 73(3): M135–M139

[97] Soni K, Jesudhasan P, Cepeda M, Williams B, Hume M, Russell W K, Jayaraman A, Pillai S D (2007). Proteomic analysis to identify the role of LuxS/AI-2 mediated protein expression in Escherichia coli O157:H7. Foodborne Pathog Dis, 4(4): 463–471

[98] Stelzmueller I, Biebl M, Wiesmayr S, Eller M, Hoeller E, Fille M, Weiss G, Lass-Floerl C, Bonatti H(2006). Ralstonia pickettii —innocent bystander or a potential threat? Clin Microbiol Infect, 12(2): 99–101

[99] Stephenson M F, Mfuna L, Dowd S E, Wolcott R D, Barbeau J, Poisson M, James G, Desrosiers M (2010). Molecular characterization of the polymicrobial flora in chronic rhinosinusitis. J Otolaryngol Head Neck Surg, 39(2): 182–187

[100] Stone A, Saiman L(2007). Update on the epidemiology and management of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, in patients with cystic fibrosis. Curr Opin Pulm Med, 13(6): 515–521

[101] Surette M G, Miller M B, Bassler B L (1999). Quorum sensing in Escherichia coli, Salmonella typhimurium, and Vibrio harveyi: a new family of genes responsible for autoinducer production. Proc Natl Acad Sci USA, 96(4): 1639–1644

[102] Swem L R, Swem D L, O’Loughlin C T, Gatmaitan R, Zhao B, Ulrich S M, Bassler B L(2009). A quorum-sensing antagonist targets both membrane-bound and cytoplasmic receptors and controls bacterial pathogenicity. Mol Cell, 35(2): 143–153

[103] Taga M E, Semmelhack J L, Bassler B L(2001). The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium. Mol Microbiol, 42(3): 777–793

[104] Tribble G D, Lamont G J, Progulske-Fox A, Lamont R J(2007). Conjugal transfer of chromosomal DNA contributes to genetic variation in the oral pathogen Porphyromonas gingivalis. J Bacteriol, 189(17): 6382–6388

[105] Ulrich L E,Zhulin I B(2007). MiST: a microbial signal transduction database. Nucleic Acids Res, 35(Database issue): D386–D390

[106] Waters C M, Bassler B L (2005). Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol, 21(1): 319–346

[107] Weimer K E, Armbruster C E, Juneau R A, Hong W, Pang B, Swords W E (2010). Coinfection with Haemophilus influenzae promotes pneumococcal biofilm formation during experimental otitis media and impedes the progression of pneumococcal disease. J Infect Dis, 202(7): 1068–1075

[108] Wellinghausen N, Essig A, Sommerburg O (2005). Inquilinus limosus in patients with cystic fibrosis, Germany. Emerg Infect Dis, 11(3): 457–459

[109] Wolcott R, Dowd S(2011). The role of biofilms: are we hitting the right target? Plast Reconstr Surg, 127 (Suppl 1): 28–35

[110] Xavier K B,Bassler B L(2005). Interference with AI-2-mediated bacterial cell-cell communication. Nature, 437(7059): 750–753

[111] Xu K D, Stewart P S, Xia F, Huang C T, McFeters G A (1998). Spatial physiological heterogeneity in Pseudomonas aeruginosa biofilm is determined by oxygen availability. Appl Environ Microbiol, 64(10): 4035–4039

[112] Zhao L, Xue T, Shang F, Sun H,Sun B(2010). Staphylococcus aureus AI-2 quorum sensing associates with the KdpDE two-component system to regulate capsular polysaccharide synthesis and virulence. Infect Immun, 78(8): 3506–3815

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