Search Advanced

AIMS Microbiology

2022, Volume 8, Issue 2: 125-137. doi: 10.3934/microbiol.2022011
Previous Article Next Article
Mini review Special Issues

Methicillin-resistant Staphylococcus aureus as a cause of chronic wound infections: Alternative strategies for management

  • 1.
    Clinic of Dermatology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy
  • 2.
    Clinic of Infectious Diseases, Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy
  • O.S. & S.M. equally contributed to the manuscript.
  • Received: 01 December 2021 Revised: 11 March 2022 Accepted: 06 April 2022 Published: 24 April 2022

  • Biofilm formation at the level of a wound plays an important role in its chronicization. The difficulty of its eradication has driven research toward the discovery and synthesis of new molecules that can act on biofilm to promote wound healing. This narrative review focuses on alternative molecules that can act and promote the eradication of methicillin-resistant Staphylococcus aureus, taking into consideration its antibiotic resistance, virulence, tendency toward the tenacious colonization of wounds by biofilms, and its increased prevalence in both community and hospital settings. A selection of promising studies were reported, analyzing the in vitro and/or in vivo efficacy of bacteriophages, metal nanoparticles, RNAIII inhibiting peptide (RIP), synthetized RIP derivatives, proteinase K and hamamelitannin.

    Citation: Oriana Simonetti, Samuele Marasca, Matteo Candelora, Giulio Rizzetto, Giulia Radi, Elisa Molinelli, Lucia Brescini, Oscar Cirioni, Annamaria Offidani. Methicillin-resistant Staphylococcus aureus as a cause of chronic wound infections: Alternative strategies for management[J]. AIMS Microbiology, 2022, 8(2): 125-137. doi: 10.3934/microbiol.2022011

    Related Papers:

  • Biofilm formation at the level of a wound plays an important role in its chronicization. The difficulty of its eradication has driven research toward the discovery and synthesis of new molecules that can act on biofilm to promote wound healing. This narrative review focuses on alternative molecules that can act and promote the eradication of methicillin-resistant Staphylococcus aureus, taking into consideration its antibiotic resistance, virulence, tendency toward the tenacious colonization of wounds by biofilms, and its increased prevalence in both community and hospital settings. A selection of promising studies were reported, analyzing the in vitro and/or in vivo efficacy of bacteriophages, metal nanoparticles, RNAIII inhibiting peptide (RIP), synthetized RIP derivatives, proteinase K and hamamelitannin.


    加载中


    Conflict of interest


    All authors declare no conflicts of interest.

    [1] Lakhundi S, Zhang K (2018) Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clin Microbiol Rev 31: e00020-18. https://doi.org/10.1128/CMR.00020-18
    [2] Vestergaard M, Frees D, Ingmer H (2019) Antibiotic resistance and the MRSA problem. Microbiol Spectr 7. https://doi.org/10.1128/microbiolspec.GPP3-0057-2018
    [3] Lerminiaux NA, Cameron ADS (2019) Horizontal tra nsfer of antibiotic resistance genes in clinical environments. Can J Microbiol 65: 34-44. https://doi.org/10.1139/cjm-2018-0275
    [4] Lindsay JA (2013) Hospital-associated MRSA and antibiotic resistance-what have we learned from genomics?. Int J Med Microbiol 303: 318-323. https://doi.org/10.1016/j.ijmm.2013.02.005
    [5] Rabin N, Zheng Y, Opoku-Temeng C, et al. (2015) Biofilm formation mechanisms and targets for developing antibiofilm agents. Future Med Chem 7: 493-512. https://doi.org/10.4155/fmc.15.6
    [6] Moormeier DE, Bayles KW (2017) Staphylococcus aureus biofilm: A complex developmental organism. Mol Microbiol 104: 365-376. https://doi.org/10.1111/mmi.13634
    [7] GBD 2015 Disease and Injury Incidence and Prevalence Collaborators.Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet (2016) 388: 1545-1602. https://doi.org/10.1016/S0140-6736(16)31678-6
    [8] Martinengo L, Olsson M, Bajpai R, et al. (2019) Prevalence of chronic wounds in the general population: Systematic review and meta-analysis of observational studies. Ann Epidemiol 29: 8-15. https://doi.org/10.1016/j.annepidem.2018.10.005
    [9] Beyene RT, Derryberry SL, Barbul A (2020) The effect of comorbidities on wound healing. Surg Clin North Am 100: 695-705. https://doi.org/10.1016/j.suc.2020.05.002
    [10] Zhao R, Liang H, Clarke E, et al. (2016) Inflammation in chronic wounds. Int J Mol Sci 17: 2085. https://doi.org/10.3390/ijms17122085
    [11] Costerton JW, Stewart PS, Greenberg EP (1999) Bacterial biofilms: A common cause of persistent infections. Science 284: 1318-1322. https://doi.org/10.1126/science.284.5418.1318
    [12] James GA, Swogger E, Wolcott R, et al. (2008) Biofilms in chronic wounds. Wound Repair Regen 16: 37-44. https://doi.org/10.1111/j.1524-475X.2007.00321.x
    [13] Bjarnsholt T (2013) The role of bacterial biofilms in chronic infections. APMIS Suppl 136: 1-51. https://doi.org/10.1111/apm.12099
    [14] Han G, Ceilley R (2017) Chronic wound healing: A review of current management and treatments. Adv Ther 34: 599-610. https://doi.org/10.1007/s12325-017-0478-y
    [15] Irie Y, Parsek MR (2008) Quorum sensing and microbial biofilms. Curr Top Microbiol Immunol 322: 67-84. https://doi.org/10.1007/978-3-540-75418-3_4
    [16] Ackermann HW (2003) Bacteriophage observations and evolution. Res Microbiol 154: 245-251. https://doi.org/10.1016/S0923-2508(03)00067-6
    [17] Silpe JE, Bassler BL (2019) A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Cell 176: 268-280.e13. https://doi.org/10.1016/j.cell.2018.10.059
    [18] Erez Z, Steinberger-Levy I, Shamir M, et al. (2017) Communication between viruses guides lysis-lysogeny decisions. Nature 541: 488-493. https://doi.org/10.1038/nature21049
    [19] Azeredo J, Sutherland IW (2008) The use of phages for the removal of infectious biofilms. Curr Pharm Biotechnol 9: 261-266. https://doi.org/10.2174/138920108785161604
    [20] Hansen MF, Svenningsen SL, Røder HL, et al. (2019) Big impact of the Ttiny: Bacteriophage-bacteria interactions in biofilms. Trends Microbiol 27: 739-752. https://doi.org/10.1016/j.tim.2019.04.006
    [21] Łusiak-Szelachowska M, Weber-Dąbrowska B, Górski A (2020) Bacteriophages and lysins in biofilm control. Virol Sin 35: 125-133. https://doi.org/10.1007/s12250-019-00192-3
    [22] Pires DP, Melo L, Vilas Boas D, et al. (2017) Phage therapy as an alternative or complementary strategy to prevent and control biofilm-related infections. Curr Opin Microbiol 39: 48-56. https://doi.org/10.1016/j.mib.2017.09.004
    [23] Doub JB, Ng VY, Johnson AJ, et al. (2020) Salvage bacteriophage therapy for a chronic MRSA prosthetic joint infection. Antibiotics (Basel) 9: 241. https://doi.org/10.3390/antibiotics9050241
    [24] Jikia D, Chkhaidze N, Imedashvili E, et al. (2005) The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin Exp Dermatol 30: 23-26. https://doi.org/10.1111/j.1365-2230.2004.01600.x
    [25] Markoishvili K, Tsitlanadze G, Katsarava R, et al. (2002) A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int J Dermatol 41: 453-458. https://doi.org/10.1046/j.1365-4362.2002.01451.x
    [26] Chhibber S, Kaur T, Sandeep K (2013) Co-therapy using lytic bacteriophage and linezolid: Effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA) from diabetic foot infections. PLoS One 8: e56022. https://doi.org/10.1371/journal.pone.0056022
    [27] El-Hamid MI, El-Naenaeey ES, Kandeel T, et al. (2020) Promising antibiofilm agents: Recent breakthrough against biofilm producing methicillin-resistant Staphylococcus aureus. Antibiotics (Basel) 9: 667. https://doi.org/10.3390/antibiotics9100667
    [28] Pelgrift RY, Friedman AJ (2013) Nanotechnology as a therapeutic tool to combat microbial resistance. Adv Drug Deliv Rev 65: 1803-1815. https://doi.org/10.1016/j.addr.2013.07.011
    [29] Cihalova K, Chudobova D, Michalek P, et al. (2015) Staphylococcus aureus and MRSA growth and biofilm formation after treatment with antibiotics and SeNPs. Int J Mol Sci 16: 24656-24672. https://doi.org/10.3390/ijms161024656
    [30] Ansari MA, Khan HM, Khan AA, et al. (2015) Anti-biofilm efficacy of silver nanoparticles against MRSA and MRSE isolated from wounds in a tertiary care hospital. Indian J Med Microbiol 33: 101-109. https://doi.org/10.4103/0255-0857.148402
    [31] Yu K, Lu F, Li Q, et al. (2017) In situ assembly of Ag nanoparticles (AgNPs) on porous silkworm cocoon-based wound film: Enhanced antimicrobial and wound healing activity. Sci Rep 7: 2107. https://doi.org/10.1038/s41598-017-02270-6
    [32] Kumar S, Majhi RK, Singh A, et al. (2019) Carbohydrate-coated gold-silver nanoparticles for efficient elimination of multidrug resistant bacteria and in vivo wound healing. ACS Appl Mater Interfaces 11: 42998-43017. https://doi.org/10.1021/acsami.9b17086
    [33] Wang Y, Dou C, He G, et al. (2018) Biomedical potential of ultrafine Ag nanoparticles coated on poly (gamma-glutamic acid) hydrogel with special reference to wound healing. Nanomaterials (Basel) 8: 324. https://doi.org/10.3390/nano8050324
    [34] Abdel-Mohsen AM, Jancar J, Abdel-Rahman RM, et al. (2017) A novel in situ silver/hyaluronan bio-nanocomposite fabrics for wound and chronic ulcer dressing: In vitro and in vivo evaluations. Int J Pharm 520: 241-253. https://doi.org/10.1016/j.ijpharm.2017.02.003
    [35] Haidari H, Bright R, Strudwick XL, et al. (2021) Multifunctional ultrasmall AgNP hydrogel accelerates healing of S. aureus infected wounds. Acta Biomater 128: 420-434. https://doi.org/10.1016/j.actbio.2021.04.007
    [36] Haidari H, Bright R, Garg S, et al. (2021) Eradication of mature bacterial biofilms with concurrent improvement in chronic wound healing using silver nanoparticle hydrogel treatment. Biomedicines 9: 1182. https://doi.org/10.3390/biomedicines9091182
    [37] Gov Y, Bitler A, Dell'Acqua G, et al. (2001) RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: Structure and function analysis. Peptides 22: 1609-1620. https://doi.org/10.1016/S0196-9781(01)00496-X
    [38] Balaban N, Goldkorn T, Gov Y, et al. (2001) Regulation of Staphylococcus aureus pathogenesis via target of RNAIII-activating Protein (TRAP). J Biol Chem 276: 2658-2667. https://doi.org/10.1074/jbc.M005446200
    [39] Gov Y, Borovok I, Korem M, et al. (2004) Quorum sensing in Staphylococci is regulated via phosphorylation of three conserved histidine residues. J Biol Chem 279: 14665-14672. https://doi.org/10.1074/jbc.M311106200
    [40] Korem M, Gov Y, Kiran MD, et al. (2005) Transcriptional profiling of target of RNAIII-activating protein, a master regulator of staphylococcal virulence. Infect Immun 73: 6220-6228. https://doi.org/10.1128/IAI.73.10.6220-6228.2005
    [41] Cirioni O, Giacometti A, Ghiselli R, et al. (2003) Prophylactic efficacy of topical temporin A and RNAIII-inhibiting peptide in a subcutaneous rat pouch model of graft infection attributable to staphylococci with intermediate resistance to glycopeptides. Circulation 108: 767-771. https://doi.org/10.1161/01.CIR.0000083717.85060.16
    [42] Cirioni O, Giacometti A, Ghiselli R, et al. (2006) RNAIII-inhibiting peptide significantly reduces bacterial load and enhances the effect of antibiotics in the treatment of central venous catheter-associated Staphylococcus aureus infections. J Infect Dis 193: 180-186. https://doi.org/10.1086/498914
    [43] Cirioni O, Ghiselli R, Minardi D, et al. (2007) RNAIII-inhibiting peptide affects biofilm formation in a rat model of staphylococcal ureteral stent infection. Antimicrob Agents Chemother 51: 4518-4520. https://doi.org/10.1128/AAC.00808-07
    [44] Simonetti O, Cirioni O, Ghiselli R, et al. (2008) RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 52: 2205-2211. https://doi.org/10.1128/AAC.01340-07
    [45] Lopez-Leban F, Kiran MD, Wolcott R, et al. (2010) Molecular mechanisms of RIP, an effective inhibitor of chronic infections. Int J Artif Organs 33: 582-589. https://doi.org/10.1177/039139881003300904
    [46] Simonetti O, Cirioni O, Mocchegiani F, et al. (2013) The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing prosthesis biofilm in an animal model of staphylococcal infection. Int J Mol Sci 14: 16321-16332. https://doi.org/10.3390/ijms140816321
    [47] Cirioni O, Mocchegiani F, Cacciatore I, et al. (2013) Quorum sensing inhibitor FS3-coated vascular graft enhances daptomycin efficacy in a rat model of staphylococcal infection. Peptides 40: 77-81. https://doi.org/10.1016/j.peptides.2012.12.002
    [48] Simonetti O, Cirioni O, Cacciatore I, et al. (2016) Efficacy of the quorum sensing inhibitor FS10 alone and in combination with tigecycline in an animal model of staphylococcal infected wound. PLoS One 11: e0151956. https://doi.org/10.1371/journal.pone.0151956
    [49] Shukla SK, Rao TS (2017) Staphylococcus aureus biofilm removal by targeting biofilm-associated extracellular proteins. Indian J Med Res 146: S1-S8. https://doi.org/10.4103/ijmr.IJMR_410_15
    [50] Kumar SS, Rao TS (2013) Dispersal of Bap-mediated Staphylococcus aureus biofilm by proteinase K. J Antibiot (Tokyo) 66: 55-60. https://doi.org/10.1038/ja.2012.98
    [51] Marquenie R (2015) Effect of hamamelitannin on staphylococcus aureus biofilm susceptibility. Ghent University Faculty of Pharmaceutical Sciences, Master of Science in Industrial Pharmacy : 5-41. Available from: https://libstore.ugent.be/fulltxt/RUG01/002/217/472/RUG01-002217472_2015_0001_AC.pdf
    [52] Brackman G, Breyne K, De Rycke R, et al. (2016) The quorum sensing inhibitor hamamelitannin increases antibiotic susceptibility of Staphylococcus aureus biofilms by affecting peptidoglycan biosynthesis and eDNA release. Sci Rep 6: 20321. https://doi.org/10.1038/srep20321
    [53] Cobrado L, Silva-Dias A, Azevedo MM, et al. (2013) In vivo antibiofilm effect of cerium, chitosan and hamamelitannin against usual agents of catheter-related bloodstream infections. J Antimicrob Chemother 68: 126-130. https://doi.org/10.1093/jac/dks376
    [54] Kiran MD, Adikesavan NV, Cirioni O, et al. (2008) Discovery of a quorum-sensing inhibitor of drug-resistant staphylococcal infections by structure-based virtual screening. Mol Pharmacol 73: 1578-1586. https://doi.org/10.1124/mol.107.044164
    [55] Kiran MD, Giacometti A, Cirioni O, et al. (2008) Suppression of biofilm related, device-associated infections by staphylococcal quorum sensing inhibitors. Int J Artif Organs 31: 761-770. https://doi.org/10.1177/039139880803100903
    [56] Vermote A, Brackman G, Risseeuw MD, et al. (2016) Novel potentiators for vancomycin in the treatment of biofilm-related MRSA infections via a mix and match approach. ACS Med Chem Lett 8: 38-42. https://doi.org/10.1021/acsmedchemlett.6b00315
    [57] Vermote A, Brackman G, Risseeuw MDP, et al. (2017) Novel hamamelitannin analogues for the treatment of biofilm related MRSA infections-A scaffold hopping approach. Eur J Med Chem 127: 757-770. https://doi.org/10.1016/j.ejmech.2016.10.056
    [58] Vermote A, Brackman G, Risseeuw MD, et al. (2016) Hamamelitannin analogues that modulate quorum sensing as potentiators of antibiotics against Staphylococcus aureus. Angew Chem Int Ed Engl 55: 6551-6555. https://doi.org/10.1002/anie.201601973
    [59] Todd DA, Parlet CP, Crosby HA, et al. (2017) Signal biosynthesis inhibition with ambuic acid as a strategy to target antibiotic-resistant infections. Antimicrob Agents Chemother 61: e00263-17. https://doi.org/10.1128/AAC.00263-17
    [60] Silvestri C, Cirioni O, Arzeni D, et al. (2012) In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against gram-positive cocci isolated from surgical wound infection. Eur J Clin Microbiol Infect Dis 31: 1759-1764. https://doi.org/10.1007/s10096-011-1498-1
    [61] Simonetti O, Cirioni O, Lucarini G, et al. (2012) Tigecycline accelerates staphylococcal-infected burn wound healing through matrix metalloproteinase-9 modulation. J Antimicrob Chemother 67: 191-201. https://doi.org/10.1093/jac/dkr440
    [62] Simonetti O, Lucarini G, Orlando F, et al. (2017) Role of daptomycin on burn wound healing in an animal methicillin-resistant Staphylococcus aureus infection model. Antimicrob Agents Chemother 61: e00606-17. https://doi.org/10.1128/AAC.00606-17
    [63] Simonetti O, Cirioni O, Orlando F, et al. (2011) Effectiveness of antimicrobial photodynamic therapy with a single treatment of RLP068/Cl in an experimental model of Staphylococcus aureus wound infection. Br J Dermatol 164: 987-995. https://doi.org/10.1111/j.1365-2133.2011.10232.x
    [64] Kopecki Z (2021) Development of next-generation antimicrobial hydrogel dressing to combat burn wound infection. Biosci Rep 41: BSR20203404. https://doi.org/10.1042/BSR20203404
    [65] Hang RYK, Morales S, Okamoto Y, et al. (2020) Topical application of bacteriophages for treatment of wound infections. Transl Res 220: 153-166. https://doi.org/10.1016/j.trsl.2020.03.010
    [66] García R, Latz S, Romero J, et al. (2019) Bacteriophage production models: An overview. Front Microbiol 10: 1187. https://doi.org/10.3389/fmicb.2019.01187
  • Reader Comments
  • © 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索
AIMS Microbiology
2.7 7.0

Metrics

Article views(3009) PDF downloads(290) Cited by(15)

Preview PDF
Download XML
Export Citation
Article outline

Other Articles By Authors

Related pages

Tools

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog