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Sustained activity of novel THIOMAB antibody-antibiotic conjugate against Staphylococcus aureus in a mouse model: Longitudinal pharmacodynamic assessment by bioluminescence imaging


Autoři: Chenguang Zhou aff001;  Hao Cai aff001;  Amos Baruch aff001;  Nicholas Lewin-Koh aff002;  Meng Yang aff003;  Fengxun Guo aff003;  Deming Xu aff003;  Rong Deng aff001;  Wouter Hazenbos aff001;  Amrita V. Kamath aff001
Působiště autorů: Research and Early Development, Genentech Inc., South San Francisco, California, United States of America aff001;  Product Development, Genentech Inc., South San Francisco, California, United States of America aff002;  WuXi AppTec (Shanghai) Co., Ltd., Shanghai, China aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0224096

Souhrn

Staphylococcus aureus (S. aureus) infections are a leading cause of death by an infectious agent. Survival within host phagocytic cells is one mechanism by which S. aureus evades antibiotic treatment. A novel THIOMAB antibody-antibiotic conjugate (TAC) strategy was developed to kill S. aureus intracellularly and mitigate the spread of infection. In this report, we used a longitudinal whole-body bioluminescence imaging method to study the antibacterial dynamics of TAC alone or in combination with vancomycin in a mouse infection model. Injections of stably luminescent S. aureus bacteria into mice resulted in exponential increases in whole body bioluminescence with a reduction in body weight and survival rate. Vancomycin, a standard-of-care antibiotic, suppressed bacterial growth in mice. However, bacterial growth rebounded in these animals once treatment was discontinued. In contrast, single dose of TAC showed rapid reduction of bioluminescence intensity, which persisted for up to 19 days. The combination of TAC and vancomycin achieved a more sustained and significantly greater reduction of bioluminescence compared with vancomycin alone. In summary, the present study showed an imaging method to longitudinally assess antibacterial drug dynamics in mice and demonstrated that TAC monotherapy or in combination with vancomycin had superior and sustained activity compared to vancomycin alone.

Klíčová slova:

Staphylococcus aureus – Antibiotics – Mouse models – Antibacterials – Vancomycin – Bioluminescence – Bacterial growth – Bioluminescence imaging


Zdroje

1. Bassetti M, Righi E, Del Giacomo P, Sartor A, Ansaldi F, Trucchi C, et al. Predictors of Mortality with Staphylococcus aureus Bacteremia in Elderly Adults. J Am Geriatr Soc. 2018.

2. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25(2):362–86. doi: 10.1128/CMR.05022-11 22491776

3. Fowler VG, Jr., Nelson CL, McIntyre LM, Kreiswirth BN, Monk A, Archer GL, et al. Potential associations between hematogenous complications and bacterial.

4. Levine DP, Fromm BS, Reddy BR. Slow response to vancomycin or vancomycin plus rifampin in methicillin-resistant Staphylococcus aureus endocarditis. Ann Intern Med. 1991;115(9):674–80. doi: 10.7326/0003-4819-115-9-674 1929035

5. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis. 2011;52(3):285–92. doi: 10.1093/cid/cir034 21217178

6. Barcia-Macay M, Seral C, Mingeot-Leclercq MP, Tulkens PM, Van Bambeke F. Pharmacodynamic evaluation of the intracellular activities of antibiotics against Staphylococcus aureus in a model of THP-1 macrophages. Antimicrob Agents Chemother. 2006;50(3):841–51. doi: 10.1128/AAC.50.3.841-851.2006 16495241

7. Thwaites GE, Gant V. Are bloodstream leukocytes Trojan Horses for the metastasis of Staphylococcus aureus? Nat Rev Microbiol. 2011;9(3):215–22. doi: 10.1038/nrmicro2508 21297670

8. Lehar SM, Pillow T, Xu M, Staben L, Kajihara KK, Vandlen R, et al. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus. Nature. 2015;527(7578):323–8. doi: 10.1038/nature16057 26536114

9. Zhou C, Lehar S, Gutierrez J, Rosenberger CM, Ljumanovic N, Dinoso J, et al. Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB antibody antibiotic conjugate against Staphylococcus aureus in mice. MAbs. 2016;8(8):1612–9. doi: 10.1080/19420862.2016.1229722 27653831

10. Rocchetta HL, Boylan CJ, Foley JW, Iversen PW, LeTourneau DL, McMillian CL, et al. Validation of a noninvasive, real-time imaging technology using bioluminescent Escherichia coli in the neutropenic mouse thigh model of infection. Antimicrobial agents and chemotherapy. 2001;Jan 1;45(1):129–37. doi: 10.1128/AAC.45.1.129-137.2001 11120955

11. Marques CN, Salisbury VC, Greenman J, Bowker KE, Nelson SM. Discrepancy between viable counts and light output as viability measurements, following ciprofloxacin challenge of self-bioluminescent Pseudomonas aeruginosa biofilms. Journal of Antimicrobial Chemotherapy. 2005;56(4), 665–671. doi: 10.1093/jac/dki285 16105852

12. Demidova TN, Gad F, Zahra T, Francis KP, Hamblin MR. Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria. Journal of Photochemistry and Photobiology B: Biology. 2005;81(1), 15–25.

13. Mortin LI, Li T, Van Praagh AD, Zhang S, Zhang XX, Alder JD. Rapid bactericidal activity of daptomycin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus peritonitis in mice as measured with bioluminescent bacteria. Antimicrob Agents Chemother. 2007;51(5):1787–94. doi: 10.1128/AAC.00738-06 17307984

14. Plaut RD, Mocca CP, Prabhakara R, Merkel TJ, Stibitz S. Stably luminescent Staphylococcus aureus clinical strains for use in bioluminescent imaging. PLoS One. 2013;8(3):e59232. doi: 10.1371/journal.pone.0059232 23555002

15. Francis KP, Joh D, Bellinger-Kawahara C, Hawkinson MJ, Purchio TF, Contag PR. Monitoring Bioluminescent Staphylococcus aureus Infections in Living Mice Using a Novel luxABCDE Construct. Infection and immunity. 2000;Jun 1;68(6):3594–600. doi: 10.1128/iai.68.6.3594-3600.2000 10816517

16. Kuklin NA, Pancari GD, Tobery TW, Cope L, Jackson J, Gill C, et al. Real-time monitoring of bacterial infection in vivo: development of bioluminescent staphylococcal foreign-body and deep-thigh-wound mouse infection models. Antimicrobial agents and chemotherapy. 2003;Sep 1;47(9):2740–8. doi: 10.1128/AAC.47.9.2740-2748.2003 12936968

17. Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD, Weir S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008;26(8):925–32. doi: 10.1038/nbt.1480 18641636

18. Staben LR, Koenig SG, Lehar SM, Vandlen R, Zhang D, Chuh J, et al. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody–drug conjugates. Nature chemistry. 2001;Dec;8(12):1112

19. Reyes N, Skinner R, Kaniga K, Krause KM, Shelton J, Obedencio GP, Gough A, Conner M, Hegde SS. Efficacy of telavancin (TD-6424), a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action, in a murine model of pneumonia induced by methicillin-resistant Staphylococcus aureus. Antimicrobial agents and chemotherapy. 2005;Oct 1;49(10):4344–6. doi: 10.1128/AAC.49.10.4344-4346.2005 16189117

20. Nielsen EI, Cars O, Friberg LE. Pharmacokinetic/pharmacodynamic (PK/PD) indices of antibiotics predicted by a semimechanistic PKPD model: a step toward model-based dose optimization. Antimicrob Agents Chemother. 2011;55(10):4619–30 doi: 10.1128/AAC.00182-11 21807983

21. Daghighi S, Sjollema J, Harapanahalli A, Dijkstra RJ, van der Mei HC, Busscher HJ. Influence of antibiotic pressure on bacterial bioluminescence, with emphasis on Staphylococcus aureus. International journal of antimicrobial agents. 2015 Dec 1;46(6):713–7. doi: 10.1016/j.ijantimicag.2015.09.007 26526893

22. Wang X, Chi H, Li Q, Li W, Li J, Li B, et al. Influence of antibiotic pressure on five plasmid-based bioluminescent gram-negative bacterial strains. Molecular Imaging and Biology. 2018 Feb 1;20(1):21–6. doi: 10.1007/s11307-017-1110-x 28791565

23. Archer NK, Mazaitis MJ, Costerton JW, Leid JG, Powers ME, Shirtliff ME. Staphylococcus aureus biofilms: properties, regulation, and roles in human disease. Virulence. 2011 Sep 1;2(5):445–59.6. doi: 10.4161/viru.2.5.17724 21921685

24. Kadurugamuwa JL, Sin L, Albert E, Yu J, Francis K, DeBoer M, et al. Direct continuous method for monitoring biofilm infection in a mouse model. Infection and immunity. 2003 Feb 1;71(2):882–90. doi: 10.1128/IAI.71.2.882-890.2003 12540570

25. Wang Y, Cheng LI, Helfer DR, Ashbaugh AG, Miller RJ, Tzomides AJ, et al. Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets. Proceedings of the National Academy of Sciences. 2017 Jun 27;114(26):E5094–102.


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