LysGH15 kills Staphylococcus aureus without being affected by the humoral immune response or inducing inflammation.

Lei Zhang, Dong Li, Xinwei Li, Liyuan Hu, Mengjun Cheng, Feifei Xia, Pengjuan Gong, Bin Wang, Jinli Ge, Hao Zhang, Ruopeng Cai, Yanmei Wang, Changjiang Sun, Xin Feng, Liancheng Lei, Wenyu Han, Jingmin Gu
Author Information
  1. Lei Zhang: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  2. Dong Li: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, P. R. China.
  3. Xinwei Li: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  4. Liyuan Hu: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  5. Mengjun Cheng: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  6. Feifei Xia: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  7. Pengjuan Gong: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  8. Bin Wang: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  9. Jinli Ge: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  10. Hao Zhang: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  11. Ruopeng Cai: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  12. Yanmei Wang: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  13. Changjiang Sun: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  14. Xin Feng: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  15. Liancheng Lei: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  16. Wenyu Han: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.
  17. Jingmin Gu: College of Veterinary Medicine, Jilin University, Changchun 130062, P. R. China.

Abstract

The lysin LysGH15, derived from the staphylococcal phage GH15, exhibits a wide lytic spectrum and highly efficient lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we found that LysGH15 did not induce resistance in MRSA or methicillin-sensitive S. aureus (MSSA) strains after repeated treatment. Although LysGH15 triggered the generation of LysGH15-specific antibodies in mice, these antibodies did not block lytic activity in vitro (nor the binding capacity of LysGH15). More importantly, when the antibody titre was highest in mice immunized with LysGH15, a single intravenous injection of LysGH15 was sufficient to protect mice against lethal infection with MRSA. These results indicated that LysGH15-specific antibodies did not affect the killing efficiency of LysGH15 against MRSA in vitro or in vivo. LysGH15 also reduced pro-inflammatory cytokines in mice with lethal infections. Furthermore, a high-dose LysGH15 injection did not cause significant adverse effects or pathological changes in the main organs of treated animals. These results provide further evidence for the administration of LysGH15 as an alternative strategy for the treatment of infections caused by MRSA.

References

  1. Bioeng Bugs. 2011 Mar-Apr;2(2):96-9 [PMID: 21636996]
  2. Future Microbiol. 2012 Oct;7(10):1147-71 [PMID: 23030422]
  3. Sci Total Environ. 2016 Apr 1;548-549:131-8 [PMID: 26802341]
  4. Curr Opin Microbiol. 2008 Oct;11(5):393-400 [PMID: 18824123]
  5. Curr Microbiol. 2011 Dec;63(6):538-42 [PMID: 21947237]
  6. Nature. 2002 Aug 22;418(6900):884-9 [PMID: 12192412]
  7. Antimicrob Agents Chemother. 2013 Jun;57(6):2743-50 [PMID: 23571534]
  8. Crit Care Med. 2009 Feb;37(2):642-9 [PMID: 19114881]
  9. Science. 2001 Dec 7;294(5549):2170-2 [PMID: 11739958]
  10. Curr Opin Pharmacol. 2003 Oct;3(5):474-9 [PMID: 14559091]
  11. PLoS One. 2013 May 28;8(5):e64671 [PMID: 23724076]
  12. Nat Rev Microbiol. 2015 Sep;13(9):529-43 [PMID: 26272408]
  13. Science. 1992 Aug 21;257(5073):1064-73 [PMID: 1509257]
  14. Appl Microbiol Biotechnol. 2015 Jan;99(2):667-80 [PMID: 25381907]
  15. Infect Immun. 2003 Nov;71(11):6199-204 [PMID: 14573637]
  16. PLoS Pathog. 2014 May 15;10(5):e1004109 [PMID: 24831957]
  17. PLoS Pathog. 2012;8(4):e1002619 [PMID: 22577358]
  18. Nat Protoc. 2008;3(2):163-75 [PMID: 18274517]
  19. Sci Total Environ. 2014 Jan 15;468-469:813-20 [PMID: 24076502]
  20. Science. 2003 Nov 28;302(5650):1569-71 [PMID: 14645850]
  21. Sci Total Environ. 2014 Sep 15;493:872-82 [PMID: 25000583]
  22. Antimicrob Agents Chemother. 2011 Feb;55(2):738-44 [PMID: 21098252]
  23. Appl Environ Microbiol. 2015 Oct 16;82(1):87-94 [PMID: 26475103]
  24. PLoS One. 2015 Jul 17;10(7):e0133196 [PMID: 26186226]
  25. Trends Microbiol. 2015 Jul;23(7):437-44 [PMID: 25864883]
  26. J Infect Dis. 2007 Oct 15;196(8):1237-47 [PMID: 17955443]
  27. Am J Pathol. 2016 Feb;186(2):212-24 [PMID: 26776074]
  28. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4107-12 [PMID: 11259652]
  29. J Clin Microbiol. 2011 Jan;49(1):111-7 [PMID: 21048011]
  30. Cell Host Microbe. 2015 Nov 11;18(5):604-12 [PMID: 26567511]
  31. FEMS Microbiol Lett. 2009 May;294(1):52-60 [PMID: 19493008]
  32. N Engl J Med. 2005 Apr 7;352(14):1445-53 [PMID: 15814880]
  33. Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4944-9 [PMID: 22411796]
  34. BMC Biotechnol. 2015 Sep 15;15:85 [PMID: 26370129]
  35. Antimicrob Agents Chemother. 2004 Jan;48(1):275-80 [PMID: 14693550]
  36. Antimicrob Agents Chemother. 2005 Nov;49(11):4789-92 [PMID: 16251333]
  37. Biochemistry. 2008 Jun 3;47(22):5915-34 [PMID: 18465878]
  38. J Immunol. 2014 May 15;192(10):4709-17 [PMID: 24729616]
  39. Mol Microbiol. 2002 Apr;44(2):335-49 [PMID: 11972774]
  40. Hybridoma (Larchmt). 2010 Aug;29(4):345-50 [PMID: 20715993]
  41. Vet Microbiol. 2016 Oct 15;194:107-111 [PMID: 26453316]
  42. Antimicrob Agents Chemother. 2010 Apr;54(4):1603-12 [PMID: 20086153]
  43. Int J Food Microbiol. 2008 Dec 10;128(2):212-8 [PMID: 18809219]
  44. J Antimicrob Chemother. 2003 Dec;52(6):967-73 [PMID: 14613958]

MeSH Term

Animals
Anti-Bacterial Agents
Female
Immunity, Humoral
Inflammation
Methicillin-Resistant Staphylococcus aureus
Mice
Mice, Inbred BALB C
Mucoproteins
Staphylococcal Infections
Staphylococcus Phages

Chemicals

Anti-Bacterial Agents
Mucoproteins
lysin, gastropoda

Word Cloud

Created with Highcharts 10.0.0LysGH15MRSAmicelyticaureusantibodiesactivityStaphylococcustreatmentLysGH15-specificvitroinjectionlethalresultsinfectionslysinderivedstaphylococcalphageGH15exhibitswidespectrumhighlyefficientmethicillin-resistantfoundinduceresistancemethicillin-sensitiveSMSSAstrainsrepeatedAlthoughtriggeredgenerationblockbindingcapacityimportantlyantibodytitrehighestimmunizedsingleintravenoussufficientprotectinfectionindicatedaffectkillingefficiencyvivoalsoreducedpro-inflammatorycytokinesFurthermorehigh-dosecausesignificantadverseeffectspathologicalchangesmainorganstreatedanimalsprovideevidenceadministrationalternativestrategycausedkillswithoutaffectedhumoralimmuneresponseinducinginflammation

Similar Articles

Cited By