Step-Wise Loss of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion
Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate that deletion of genes coding for the flagellar stator complex, which results in non-swimming bacteria that retain an initial flagellar structure, confers resistance to phagocytic binding and ingestion in several species of the gamma proteobacterial group of Gram-negative bacteria, indicative of a shared strategy for phagocytic evasion. Furthermore, we show for the first time that susceptibility to phagocytosis in swimming bacteria is proportional to mot gene function and, consequently, flagellar rotation since complementary genetically- and biochemically-modulated incremental decreases in flagellar motility result in corresponding and proportional phagocytic evasion. These findings identify that phagocytic cells respond to flagellar movement, which represents a novel mechanism for non-opsonized phagocytic recognition of pathogenic bacteria.
Vyšlo v časopise:
Step-Wise Loss of Bacterial Flagellar Torsion Confers Progressive Phagocytic Evasion. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002253
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002253
Souhrn
Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate that deletion of genes coding for the flagellar stator complex, which results in non-swimming bacteria that retain an initial flagellar structure, confers resistance to phagocytic binding and ingestion in several species of the gamma proteobacterial group of Gram-negative bacteria, indicative of a shared strategy for phagocytic evasion. Furthermore, we show for the first time that susceptibility to phagocytosis in swimming bacteria is proportional to mot gene function and, consequently, flagellar rotation since complementary genetically- and biochemically-modulated incremental decreases in flagellar motility result in corresponding and proportional phagocytic evasion. These findings identify that phagocytic cells respond to flagellar movement, which represents a novel mechanism for non-opsonized phagocytic recognition of pathogenic bacteria.
Zdroje
1. AkiraSUematsuSTakeuchiO 2006 Pathogen recognition and innate immunity. Cell 124 783 801
2. LyczakJBCannonCLPierGB 2000 Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2 1051 1060
3. LyczakJBCannonCLPierGB 2002 Lung infections associated with cystic fibrosis. Clin Microbiol Rev 15 194 222
4. AmielELovewellRRO'TooleGAHoganDABerwinB 2010 Pseudomonas aeruginosa evasion of phagocytosis is mediated by loss of swimming motility and is independent of flagellum expression. Infect Immun 78 2937 2945
5. BalloyVVermaAKuraviSSi-TaharMChignardM 2007 The role of flagellin versus motility in acute lung disease caused by Pseudomonas aeruginosa. J Infect Dis 196 289 296
6. LuzarMAThomassenMJMontieTC 1985 Flagella and motility alterations in Pseudomonas aeruginosa strains from patients with cystic fibrosis: relationship to patient clinical condition. Infect Immun 50 577 582
7. MahenthiralingamECampbellMESpeertDP 1994 Nonmotility and phagocytic resistance of Pseudomonas aeruginosa isolates from chronically colonized patients with cystic fibrosis. Infect Immun 62 596 605
8. MahenthiralingamESpeertDP 1995 Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum. Infect Immun 63 4519 4523
9. ToutainCMZegansMEO'TooleGA 2005 Evidence for two flagellar stators and their role in the motility of Pseudomonas aeruginosa. J. Bacteriol 187 771 777
10. TerashimaHKojimaSHommaM 2008 Flagellar motility in bacteria structure and function of flagellar motor. Int Rev Cell Mol Biol 270 39 85
11. DeRosierDJ 1998 The turn of the screw: the bacterial flagellar motor. Cell 93 17 20
12. MartinezRMDharmasenaMNKirnTJTaylorRK 2009 Characterization of two outer membrane proteins, FlgO and FlgP, that influence vibrio cholerae motility. J Bacteriol 191 5669 5679
13. BraunTFPSGullyJBEmpeyJCVan WaySPutnamA 1999 Function of proline residues of MotA in torque generation by the flagellar motor of Escherichia coli. J Bacteriol 181 3542 3551
14. DoyleTBHawkinsACMcCarterLL 2004 The complex flagellar torque generator of Pseudomonas aeruginosa. J Bacteriol 186 6341 6350
15. GosinkKKHaseCC 2000 Requirements for conversion of the Na(+)-driven flagellar motor of Vibrio cholerae to the H(+)-driven motor of Escherichia coli. J Bacteriol 182 4234 4240
16. PrittBO'BrienLWinnW 2007 Mucoid Pseudomonas in cystic fibrosis. Am J Clin Pathol 128 32 34
17. OhmanDEChakrabartyAM 1981 Genetic mapping of chromosomal determinants for the production of the exopolysaccharide alginate in a Pseudomonas aeruginosa cystic fibrosis isolate. Infect Immun 33 142 148
18. HulbertRRTaylorRK 2002 Mechanism of ToxT-dependent transcriptional activation at the Vibrio cholerae tcpA promoter. J Bacteriol 184 5533 5544
19. StonehouseEKovacikovaGTaylorRKSkorupskiK 2008 Integration host factor positively regulates virulence gene expression in Vibrio cholerae. J Bacteriol 190 4736 4748
20. SunDXMekalanosJJTaylorRK 1990 Antibodies directed against the toxin-coregulated pilus isolated from Vibrio cholerae provide protection in the infant mouse experimental cholera model. J Infect Dis 161 1231 1236
21. SantosLRodriguesDLiraMOliveiraRReal OliveiraME 2007 The effect of octylglucoside and sodium cholate in Staphylococcus epidermidis and Pseudomonas aeruginosa adhesion to soft contact lenses. Optom Vis Sci 84 429 434
22. KandaETatsutaTSuzukiTTaguchiFNaitoK 2010 Two flagellar stators and their roles in motility and virulence in Pseudomonas syringae pv. tabaci 6605. Mol Genet Genomics
23. KojimaSYamamotoKKawagishiIHommaM 1999 The polar flagellar motor of Vibrio cholerae is driven by an Na+ motive force. J Bacteriol 181 1927 1930
24. AroraSKRitchingsBWAlmiraECLorySRamphalR 1998 The Pseudomonas aeruginosa flagellar cap protein, FliD, is responsible for mucin adhesion. Infect Immun 66 1000 1007
25. AttridgeSRRowleyD 1983 The role of the flagellum in the adherence of Vibrio cholerae. J Infect Dis 147 864 872
26. GironJATorresAGFreerEKaperJB 2002 The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol Microbiol 44 361 379
27. BirukovKGShirinskyVPStepanovaOVTkachukVAHahnAW 1995 Stretch affects phenotype and proliferation of vascular smooth muscle cells. Mol Cell Biochem 144 131 139
28. FingerEBPuriKDAlonRLawrenceMBvon AndrianUH 1996 Adhesion through L-selectin requires a threshold hydrodynamic shear. Nature 379 266 269
29. DrakeDMontieTC 1988 Flagella, motility and invasive virulence of Pseudomonas aeruginosa. J Gen Microbiol 134 43 52
30. FreterRJonesGW 1976 Adhesive properties of Vibrio cholerae: nature of the interaction with intact mucosal surfaces. Infect Immun 14 246 256
31. PierGBMeluleniGGoldbergJB 1995 Clearance of Pseudomonas aeruginosa from the murine gastrointestinal tract is effectively mediated by O-antigen-specific circulating antibodies. Infect Immun 63 2818 2825
32. SiitonenANurminenM 1992 Bacterial motility is a colonization factor in experimental urinary tract infection. Infect Immun 60 3918 3920
33. InabaKInabaMDeguchiMHagiKYasumizuR 1993 Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc Natl Acad Sci U S A 90 3038 3042
34. BloembergGVO'TooleGALugtenbergBJJKolterR 1997 Green fluorescent protein as a marker for Pseudomonas spp. Appl Environ Microbiol 63 4543 4551
35. MacFerrinKDTerranovaMPSchreiberSLVerdineGL 1990 Overproduction and dissection of proteins by the expression-cassette polymerase chain reaction. Proc Natl Acad Sci U S A 87 1937 1941
36. DuncanMJLiGShinJSCarsonJLAbrahamSN 2004 Bacterial penetration of bladder epithelium through lipid rafts. J Biol Chem 279 18944 18951
37. R Development Core Team 2009 R: A Language and Environment for Statistical Computing. http://www.R-project.org
38. GentlemanR 2005 Bioinformatics and computational biology solutions using R and Bioconductor, in Statistics for biology and health. Vol. xix New york Springer Science+Business Media 473
39. GentlemanRCCareyVJBatesDMBolstadBDettlingM 2004 Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5 R80
40. BolstadBMIrizarryRAAstrandMSpeedTP 2003 A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19 185 193
41. IrizarryRABolstadBMCollinFCopeLMBHobbs 2003 Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31 e15
42. BengtssonHSimpsonKBullardJHansenK 2008 aroma.affymetrix: A generic framework in R for analyzing small to very large Affymetrix data sets in bounded memory, in Technical Report #745, Department of Statistics, University of California, Berkeley
43. WilsonCLMillerCJ 2005 Simpleaffy: a BioConductor package for Affymetrix Quality Control and data analysis. Bioinformatics 21 3683 3685
44. ParmanCHallingCGentlemanR 2005 affyQCReport: QC Report Generation for affyBatch objects
45. BatesDMoechlerMDaiB 2008 lme4: Linear mixed-effects models using S4 classes
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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