CRISPR-Cas9 modified bacteriophage for treatment of Staphylococcus aureus induced osteomyelitis and soft tissue infection
Autoři:
Leah H. Cobb aff001; JooYoun Park aff002; Elizabeth A. Swanson aff003; Mary Catherine Beard aff001; Emily M. McCabe aff001; Anna S. Rourke aff001; Keun Seok Seo aff002; Alicia K. Olivier aff004; Lauren B. Priddy aff001
Působiště autorů:
Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, Mississippi, United States of America
aff001; Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America
aff002; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America
aff003; Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, United States of America
aff004
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0220421
Souhrn
Osteomyelitis, or bone infection, is often induced by antibiotic resistant Staphylococcus aureus strains of bacteria. Although debridement and long-term administration of antibiotics are the gold standard for osteomyelitis treatment, the increase in prevalence of antibiotic resistant bacterial strains limits the ability of clinicians to effectively treat infection. Bacteriophages (phages), viruses that in a lytic state can effectively kill bacteria, have gained recent attention for their high specificity, abundance in nature, and minimal risk of host toxicity. Previously, we have shown that CRISPR-Cas9 genomic editing techniques could be utilized to expand temperate bacteriophage host range and enhance bactericidal activity through modification of the tail fiber protein. In a dermal infection study, these CRISPR-Cas9 phages reduced bacterial load relative to unmodified phage. Thus we hypothesized this temperate bacteriophage, equipped with the CRISPR-Cas9 bactericidal machinery, would be effective at mitigating infection from a biofilm forming S. aureus strain in vitro and in vivo. In vitro, qualitative fluorescent imaging demonstrated superiority of phage to conventional vancomycin and fosfomycin antibiotics against S. aureus biofilm. Quantitative antibiofilm effects increased over time, at least partially, for all fosfomycin, phage, and fosfomycin-phage (dual) therapeutics delivered via alginate hydrogel. We developed an in vivo rat model of osteomyelitis and soft tissue infection that was reproducible and challenging and enabled longitudinal monitoring of infection progression. Using this model, phage (with and without fosfomycin) delivered via alginate hydrogel were successful in reducing soft tissue infection but not bone infection, based on bacteriological, histological, and scanning electron microscopy analyses. Notably, the efficacy of phage at mitigating soft tissue infection was equal to that of high dose fosfomycin. Future research may utilize this model as a platform for evaluation of therapeutic type and dose, and alternate delivery vehicles for osteomyelitis mitigation.
Klíčová slova:
Staphylococcus aureus – Antibiotics – Bacteriophages – Bacterial biofilms – Gels – Osteomyelitis – Vancomycin – Soft tissue infections
Zdroje
1. Center for Disease Control and Prevention. Antibiotic Use in the United States, 2017: Progress and Opportunities. US Dep Heal Hum Serv. 2017.
2. Thorpe KE, Joski P, Johnston KJ. Antibiotic-Resistant Infection Treatment Costs Have Doubled Since 2002, Now Exceeding $2 Billion Annually. Health Aff (Millwood). United States; 2018;37: 662–669. doi: 10.1377/hlthaff.2017.1153 29561692
3. O’Neill J. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. Rev Antimicrob Resist. 2014;
4. Tom Frieden. Antibiotic Resistance Threats. Cdc. 2013; CS239559-B
5. Archer NK, Mazaitis MJ, William Costerton J, Leid JG, Powers ME, Shirtliff ME. Staphylococcus aureus biofilms: Properties, regulation and roles in human disease. Virulence. 2011. doi: 10.4161/viru.2.5.17724 21921685
6. Johnson CT, Wroe JA, Agarwal R, Martin KE, Guldberg RE, Donlan RM, et al. Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing. Proc Natl Acad Sci. 2018; doi: 10.1073/pnas.1801013115 29760099
7. Geraghty T, LaPorta G. Current health and economic burden of chronic diabetic osteomyelitis. Expert Review of Pharmacoeconomics and Outcomes Research. 2019. doi: 10.1080/14737167.2019.1567337 30625012
8. Rowley WR, Bezold C, Arikan Y, Byrne E, Krohe S. Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Popul Health Manag. 2017; doi: 10.1089/pop.2015.0181 27124621
9. Abatángelo V, Peressutti Bacci N, Boncompain CA, Amadio AA, Carrasco S, Suárez CA, et al. Broad-range lytic bacteriophages that kill Staphylococcus aureus local field strains. PLoS One. 2017; doi: 10.1371/journal.pone.0181671 28742812
10. Tang Z, Huang X, Sabour PM, Chambers JR, Wang Q. Preparation and characterization of dry powder bacteriophage K for intestinal delivery through oral administration. LWT—Food Sci Technol. 2015; doi: 10.1016/j.lwt.2014.08.012
11. Furfaro LL, Payne MS, Chang BJ. Bacteriophage Therapy: Clinical Trials and Regulatory Hurdles. Front Cell Infect Microbiol. 2018; doi: 10.3389/fcimb.2018.00376 30406049
12. Wright A, Hawkins CH, Änggård EE, Harper DR. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol. Wiley/Blackwell (10.1111); 2009;34: 349–357. doi: 10.1111/j.1749-4486.2009.01973.x 19673983
13. Leitner L, Sybesma W, Chanishvili N, Goderdzishvili M, Chkhotua A, Ujmajuridze A, et al. Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: A randomized, placebo-controlled, double-blind clinical trial. BMC Urol. 2017; doi: 10.1186/s12894-017-0283-6 28950849
14. Fabijan AP, Lin RCY, Ho J, Maddocks S, Iredell JR. Safety and Tolerability of Bacteriophage Therapy in Severe Staphylococcus aureus Infection. bioRxiv. 2019; 619999. doi: 10.1101/619999
15. Voelker R. FDA Approves Bacteriophage TrialFDA Approves Bacteriophage TrialNews From the Food and Drug Administration. JAMA. 2019;321: 638. doi: 10.1001/jama.2019.0510 30778586
16. Johnson C, Dinjaski N, Prieto M, García A. Bacteriophage Encapsulation in Poly(Ethylene Glycol) Hydrogels Significantly Reduces Bacteria Numbers in an Implant-Associated Infection Model of Bone Repair. Igarss 2014.
17. Bean JE, Alves DR, Laabei M, Esteban PP, Thet NT, Enright MC, et al. Triggered Release of Bacteriophage K from Agarose/Hyaluronan Hydrogel Matrixes by Staphylococcus aureus Virulence Factors [Internet]. CHEMISTRY OF MATERIALS. pp. 7201–7208. doi: 10.1021/cm503974g
18. Priddy LB, Chaudhuri O, Stevens HY, Krishnan L, Uhrig BA, Willett NJ, et al. Oxidized alginate hydrogels for bone morphogenetic protein-2 delivery in long bone defects. Acta Biomater. 2014/06/17. 2014;10: 4390–4399. doi: 10.1016/j.actbio.2014.06.015 24954001
19. Krishnan L, Priddy LB, Esancy C, Li MTA, Stevens HY, Jiang X, et al. Hydrogel-based Delivery of rhBMP-2 Improves Healing of Large Bone Defects Compared With Autograft. Clin Orthop Relat Res. 2015; doi: 10.1007/s11999-015-4312-z 25917422
20. Souza GR, Yonel-Gumruk E, Fan D, Easley J, Rangel R, Guzman-Rojas L, et al. Bottom-up assembly of hydrogels from bacteriophage and Au nanoparticles: The effect of Cis- and trans-acting factors. PLoS One. 2008; doi: 10.1371/journal.pone.0002242 18493583
21. Park JY, Moon BY, Park JW, Thornton JA, Park YH, Seo KS. Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus. Sci Rep. 2017;7: 44929. Available: http://dx.doi.org/10.1038/srep44929
22. De Jong NWM, Van Der Horst T, Van Strijp JAG, Nijland R. Fluorescent reporters for markerless genomic integration in Staphylococcus aureus. Sci Rep. 2017; doi: 10.1038/srep43889 28266573
23. Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. England; 1966;45: 493–496.
24. Karnovsky MJ. A Formaldehyde-Glutaraldehyde Fixative of High Osmolality for Use in Electron Microscopy. The American Society for Cell Biology Source: The Journal of Cell Biology. 1965.
25. Kristensen HK. An Improved Method of Decalcification. Stain Technol. Taylor & Francis; 1948;23: 151–154. doi: 10.3109/10520294809106242 18867628
26. Krishnan L, Priddy LB, Esancy C, Klosterhoff BS, Stevens HY, Tran L, et al. Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2. Acta Biomater. 2017; doi: 10.1016/j.actbio.2016.12.012 27940197
27. Lodise TP, Lomaestro B, Graves J, Drusano GL. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother. 2008; doi: 10.1128/AAC.01602-07 18227177
28. Weinstein RA, Fridkin SK. Vancomycin-Intermediate and -Resistant Staphylococcus aureus: What the Infectious Disease Specialist Needs to Know. Clin Infect Dis. 2001;32: 108–115. doi: 10.1086/317542 11118389
29. Wang F, Zhou H, Olademehin OP, Kim SJ, Tao P. Insights into key interactions between vancomycin and bacterial cell wall structures. ACS Omega. 2018; doi: 10.1021/acsomega.7b01483 29399648
30. Trautmann M, Meincke C, Vogt K, Ruhnke M, Lajous-Petter AM. Intracellular bactericidal activity of fosfomycin against staphylococci: A comparison with other antibiotics. Infection. 1992; doi: 10.1007/BF01710683 1293056
31. Poeppl W, Lingscheid T, Bernitzky D, Schwarze UY, Donath O, Perkmann T, et al. Efficacy of fosfomycin compared to vancomycin in treatment of implant-associated chronic methicillin-resistant Staphylococcus aureus osteomyelitis in rats. Antimicrob Agents Chemother. 2014; doi: 10.1128/AAC.02720-13 24936591
32. Dijkmans AC, Zacarías NVO, Burggraaf J, Mouton JW, Wilms E, van Nieuwkoop C, et al. Fosfomycin: Pharmacological, Clinical and Future Perspectives. Antibiotics. 2017; doi: 10.3390/antibiotics6040024 29088073
33. Takahata S, Ida T, Hiraishi T, Sakakibara S, Maebashi K, Terada S, et al. Molecular mechanisms of fosfomycin resistance in clinical isolates of Escherichia coli. Int J Antimicrob Agents. 2010; doi: 10.1016/j.ijantimicag.2009.11.011 20071153
34. Alves DR, Gaudion A, Bean JE, Perez Esteban P, Arnot TC, Harper DR, et al. Combined Use of Bacteriophage K and a Novel Bacteriophage To Reduce Staphylococcus aureus Biofilm Formation. Appl Environ Microbiol. 2014; doi: 10.1128/aem.01789-14 25149517
35. Pincus NB, Reckhow JD, Saleem D, Jammeh ML, Datta SK, Myles IA. Strain specific phage treatment for Staphylococcus aureus infection is influenced by host immunity and site of infection. PLoS One. 2015; doi: 10.1371/journal.pone.0124280 25909449
36. Koo V, Hamilton PW, Williamson K. Non-invasive in vivo imaging in small animal research. Cellular Oncology. 2006.
37. Nelson CL, McLaren SG, Skinner RA, Smeltzer MS, Thomas JR, Olsen KM. The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets. J Orthop Res. 2002; doi: 10.1016/S0736-0266(01)00133-4
38. Taki H, Krkovic M, Moore E, Abood A, Norrish A. Chronic long bone osteomyelitis: diagnosis, management and current trends. Br J Hosp Med. 2016; doi: 10.12968/hmed.2016.77.10.c161 27723401
39. Berbari EF, Kanj SS, Kowalski TJ, Darouiche RO, Widmer AF, Schmitt SK, et al. 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adultsa. Clinical Infectious Diseases. 2015. doi: 10.1093/cid/civ633 26316526
40. Fish R, Kutter E, Bryan D, Wheat G, Kuhl S. Resolving Digital Staphylococcal Osteomyelitis Using Bacteriophage—A Case Report. Antibiotics. 2018; doi: 10.3390/antibiotics7040087 30279396
41. de Mesy Bentley KL, Trombetta R, Nishitani K, Bello-Irizarry SN, Ninomiya M, Zhang L, et al. Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis. J Bone Miner Res. 2017; doi: 10.1002/jbmr.3055 27933662
42. Kishor C, Mishra RR, Saraf SK, Kumar M, Srivastav AK, Nath G. Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model. Indian J Med Res. 2016; doi: 10.4103/0971-5916.178615 26997019
43. Ibrahim OMS, Sarhan SR, Salih SI. Activity of Isolated Staphylococcal Bacteriophage in Treatment of Experimentally Induced Chronic Osteomyelitis in Rabbits. Adv Anim Vet Sci. 2016; doi: 10.14737/journal.aavs/2016/4.11.593.603
44. Lopes A, Pereira C, Almeida A. Sequential Combined Effect of Phages and Antibiotics on the Inactivation of Escherichia coli. Microorganisms. MDPI; 2018;6: 125. doi: 10.3390/microorganisms6040125 30563133
45. Tagliaferri TL, Jansen M, Horz H-P. Fighting Pathogenic Bacteria on Two Fronts: Phages and Antibiotics as Combined Strategy [Internet]. Frontiers in Cellular and Infection Microbiology. 2019. p. 22. Available: https://www.frontiersin.org/article/10.3389/fcimb.2019.00022 30834237
Článok vyšiel v časopise
PLOS One
2019 Číslo 11
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Dlouhodobá recidiva a komplikace spojené s elektivní operací břišní kýly
Najčítanejšie v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF