Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in

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Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower respiratory tracts. An important aspect of NTHI virulence is the ability to avert bactericidal effects of host-derived antimicrobial peptides (AMPs). The Sap (sensitivity to antimicrobial peptides) ABC transporter equips NTHI to resist AMPs, although the mechanism of this resistance has remained undefined. We previously determined that the periplasmic binding protein SapA bound AMPs and was required for NTHI virulence in vivo. We now demonstrate, by antibody-mediated neutralization of AMP in vivo, that SapA functions to directly counter AMP lethality during NTHI infection. We hypothesized that SapA would deliver AMPs to the Sap inner membrane complex for transport into the bacterial cytoplasm. We observed that AMPs localize to the bacterial cytoplasm of the parental NTHI strain and were susceptible to cytoplasmic peptidase activity. In striking contrast, AMPs accumulated in the periplasm of bacteria lacking a functional Sap permease complex. These data support a mechanism of Sap mediated import of AMPs, a novel strategy to reduce periplasmic and inner membrane accumulation of these host defense peptides.

Vyšlo v časopise: Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002360
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002360

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Zdroje

1. BrogdenKA 2005 Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 3 238 250

2. SitaramNNagarajR 2002 Host-defense antimicrobial peptides: importance of structure for activity. Curr Pharm Des 8 727 742

3. StolzenbergEDAndersonGMAckermannMRWhitlockRHZasloffM 1997 Epithelial antibiotic induced in states of disease. Proc Natl Acad Sci U S A 94 8686 8690

4. HarderJBartelsJChristophersESchroderJM 2001 Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276 5707 5713

5. SorensenOArnljotsKCowlandJBBaintonDFBorregaardN 1997 The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood 90 2796 2803

6. BalsRWangXZasloffMWilsonJM 1998 The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci U S A 95 9541 9546

7. SalzmanNHGhoshDHuttnerKMPatersonYBevinsCL 2003 Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature 422 522 526

8. SelstedMEOuelletteAJ 2005 Mammalian defensins in the antimicrobial immune response. Nat Immunol 6 551 557

9. LehrerRI 2004 Paradise lost and paradigm found. Nat Immunol 5 775 776

10. LaubeDMYimSRyanLKKisichKODiamondG 2006 Antimicrobial peptides in the airway. Curr Top Microbiol Immunol 306 153 182

11. NizetVOhtakeTLauthXTrowbridgeJRudisillJ 2001 Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414 454 457

12. PeschelA 2002 How do bacteria resist human antimicrobial peptides? Trends Microbiol 10 179 186

13. ErnstRKGuinaTMillerSI 2001 Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity. Microbes Infect 3 1327 1334

14. KawasakiK 2006 [Outer membrane remodeling of Salmonella typhimurium and host innate immunity]. Yakugaku Zasshi 126 1227 1234

15. ShaferWMQuXWaringAJLehrerRI 1998 Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci U S A 95 1829 1833

16. Sieprawska-LupaMMydelPKrawczykKWojcikKPukloM 2004 Degradation of human antimicrobial peptide LL-37 by Staphylococcus aureus-derived proteinases. Antimicrob Agents Chemother 48 4673 4679

17. IslamDBandholtzLNilssonJWigzellHChristenssonB 2001 Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7 180 185

18. AttiaASBensonMAStauffDLTorresVJSkaarEP 2010 Membrane damage elicits an immunomodulatory program in Staphylococcus aureus. PLoS Pathog 6 e1000802

19. FrickIMAkessonPRasmussenMSchmidtchenABjorckL 2003 SIC, a secreted protein of Streptococcus pyogenes that inactivates antibacterial peptides. J Biol Chem 278 16561 16566

20. KleinJO 1997 Role of nontypeable Haemophilus influenzae in pediatric respiratory tract infections. Pediatr Infect Dis J 16 S5 8

21. KilpiTHervaEKaijalainenTSyrjanenRTakalaAK 2001 Bacteriology of acute otitis media in a cohort of Finnish children followed for the first two years of life. Pediatr Infect Dis J 20 654 662

22. PatelPBDiazMCBennettJEAttiaMW 2007 Clinical features of bacterial conjunctivitis in children. Acad Emerg Med 14 1 5

23. BrookI 2002 Bacteriology of acute and chronic frontal sinusitis. Arch Otolaryngol Head Neck Surg 128 583 585

24. SethiS 2000 Bacterial infection and the pathogenesis of COPD. Chest 117 286S 291S

25. RomanFCantonRPerez-VazquezMBaqueroFCamposJ 2004 Dynamics of long-term colonization of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains. J Clin Microbiol 42 1450 1459

26. LysenkoESGouldJBalsRWilsonJMWeiserJN 2000 Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect Immun 68 1664 1671

27. StarnerTDSwordsWEApicellaMAMcCrayPBJr 2002 Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation. Infect Immun 70 5287 5289

28. GroismanEAParra-LopezCSalcedoMLippsCJHeffronF 1992 Resistance to host antimicrobial peptides is necessary for Salmonella virulence. Proc Natl Acad Sci U S A 89 11939 11943

29. Parra-LopezCBaerMTGroismanEA 1993 Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium. Embo J 12 4053 4062

30. Parra-LopezCLinRAspedonAGroismanEA 1994 A Salmonella protein that is required for resistance to antimicrobial peptides and transport of potassium. Embo J 13 3964 3972

31. EswarappaSMPanguluriKKHenselMChakravorttyD 2008 The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiology 154 666 678

32. Lopez-SolanillaEGarcia-OlmedoFRodriguez-PalenzuelaP 1998 Inactivation of the sapA to sapF locus of Erwinia chrysanthemi reveals common features in plant and animal bacterial pathogenesis. Plant Cell 10 917 924

33. ChenHYWengSFLinJW 2000 Identification and analysis of the sap genes from Vibrio fischeri belonging to the ATP-binding cassette gene family required for peptide transport and resistance to antimicrobial peptides. Biochem Biophys Res Commun 269 743 748

34. HarmsCDomotoYCelikCRaheEStumpeS 2001 Identification of the ABC protein SapD as the subunit that confers ATP dependence to the K+-uptake systems Trk(H) and Trk(G) from Escherichia coli K-12. Microbiology 147 2991 3003

35. RodasPIContrerasIMoraGC 2010 Salmonella enterica serovar Typhi has a 4.1 kb genetic island inserted within the sapABCDF operon that causes loss of resistance to the antimicrobial peptide protamine. J Antimicrob Chemother 65 1624 1630

36. MountKLTownsendCARinkerSDGuXFortneyKR 2010 Haemophilus ducreyi SapA contributes to cathelicidin resistance and virulence in humans. Infect Immun 78 1176 1184

37. MasonKMBruggemanMEMunsonRSBakaletzLO 2006 The non-typeable Haemophilus influenzae Sap transporter provides a mechanism of antimicrobial peptide resistance and SapD-dependent potassium acquisition. Mol Microbiol 62 1357 1372

38. MasonKMMunsonRSJrBakaletzLO 2005 A mutation in the sap operon attenuates survival of nontypeable Haemophilus influenzae in a chinchilla model of otitis media. Infect Immun 73 599 608

39. MasonKMRaffelFKRayWCBakaletzLO 2011 Heme Utilization by Nontypeable Haemophilus influenzae is Essential and Dependent on Sap Transporter Function. J Bacteriol 193 2527 35

40. ChromekMSlamovaZBergmanPKovacsLPodrackaL 2006 The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12 636 641

41. McGillivaryGMasonKMJurcisekJAPeeplesMEBakaletzLO 2009 Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae. Cell Microbiol 11 1399 1408

42. McGillivaryGRayWCBevinsCLMunsonRSJrBakaletzLO 2007 A member of the cathelicidin family of antimicrobial peptides is produced in the upper airway of the chinchilla and its mRNA expression is altered by common viral and bacterial co-pathogens of otitis media. Mol Immunol 44 2446 2458

43. LimDJChunYMLeeHYMoonSKChangKH 2000 Cell biology of tubotympanum in relation to pathogenesis of otitis media - a review. Vaccine 19 Suppl 1 S17 25

44. GunnJSMillerSI 1996 PhoP-PhoQ activates transcription of pmrAB, encoding a two-component regulatory system involved in Salmonella typhimurium antimicrobial peptide resistance. J Bacteriol 178 6857 6864

45. McPheeJBBainsMWinsorGLewenzaSKwasnickaA 2006 Contribution of the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems to Mg2+-induced gene regulation in Pseudomonas aeruginosa. J Bacteriol 188 3995 4006

46. BengoecheaJASkurnikM 2000 Temperature-regulated efflux pump/potassium antiporter system mediates resistance to cationic antimicrobial peptides in Yersinia. Mol Microbiol 37 67 80

47. RinkerSDTrombleyMPGuXFortneyKRBauerME 2011 Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon. Infect Immun 79 2324 34

48. HarrisRHWilkDBevinsCLMunsonRSJrBakaletzLO 2004 Identification and characterization of a mucosal antimicrobial peptide expressed by the chinchilla (Chinchilla lanigera) airway. J Biol Chem 279 20250 20256

49. IimuraMGalloRLHaseKMiyamotoYEckmannL 2005 Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 174 4901 4907

50. ShinnarAEButlerKLParkHJ 2003 Cathelicidin family of antimicrobial peptides: proteolytic processing and protease resistance. Bioorg Chem 31 425 436

51. SugimuraKHigashiN 1988 A novel outer-membrane-associated protease in Escherichia coli. J Bacteriol 170 3650 3654

52. SodeindeOASubrahmanyamYVStarkKQuanTBaoY 1992 A surface protease and the invasive character of plague. Science 258 1004 1007

53. GuinaTYiECWangHHackettMMillerSI 2000 A PhoP-regulated outer membrane protease of Salmonella enterica serovar typhimurium promotes resistance to alpha-helical antimicrobial peptides. J Bacteriol 182 4077 4086

54. YeamanMRYountNY 2003 Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55 27 55

55. BotosIMelnikovEECherrySKhalatovaAGRasulovaFS 2004 Crystal structure of the AAA+ alpha domain of E. coli Lon protease at 1.9A resolution. J Struct Biol 146 113 122

56. McGillivraySMEbrahimiCMFisherNSabetMZhangDX 2009 ClpX contributes to innate defense peptide resistance and virulence phenotypes of Bacillus anthracis. J Innate Immun 1 494 506

57. HancockRE 1997 Peptide antibiotics. Lancet 349 418 422

58. HarrisonADyerDWGillaspyARayWCMungurR 2005 Genomic sequence of an otitis media isolate of nontypeable Haemophilus influenzae: comparative study with H. influenzae serotype d, strain KW20. J Bacteriol 187 4627 4636

59. HarrisonARayWCBakerBDArmbrusterDWBakaletzLO 2007 The OxyR regulon in nontypeable Haemophilus influenzae. J Bacteriol 189 1004 1012

60. TracyEYeFBakerBDMunsonRSJr 2008 Construction of non-polar mutants in Haemophilus influenzae using FLP recombinase technology. BMC Mol Biol 9 101

61. WangBClearyPPXuHLiJD 2003 Up-regulation of interleukin-8 by novel small cytoplasmic molecules of nontypeable Haemophilus influenzae via p38 and extracellular signal-regulated kinase pathways. Infect Immun 71 5523 5530