Microbial biofilm inhibits wound healing

From MicrobeWiki, the student-edited microbiology resource

Introduction

Figure 1. Inflammatory phase of wound healing. Chronic wounds are arrested in this phase and are unable to move forward in the wound healing process. Source: Assessment Technologies Institute of Nursing Education, “Wound Care: The anatomy and physiology of wound healing” (http://www.atitesting.com/ati_next_gen/skillsmodules/content/wound-care/equipment/a_and_p.html).


By Katie Kaestner


When someone suffers an injury to the skin, such as a laceration or an abrasion, the tissue normally undergoes four basic stages of wound healing. The inflammatory phase initiates the process, during which the body’s immune system sends nutrients, platelets, white blood cells (namely neutrophils, lymphocytes, and macrophages), antibodies, enzymes, and other immune factors to the affected area to establish homeostasis and prevent infection. Keratinocytes and inflammatory cytokines are then recruited to the area as the wound enters the epithelialization phase, providing temporary protection and activating the next phase of proliferation. A scab is a result of the epithelialization stage. After a few days, fibroblasts and collagen regenerate tissue and blood vessels in the proliferation stage, until finally reaching the remodeling stage in which collagen is continually formed and lysed until the skin is restored to its original strength.[1]

However, some wounds may be arrested in the inflammatory phase (Figure 1). These wounds, referred to as chronic wounds, may take weeks, months, or years to heal, and become highly susceptible to bacterial infection without persistent care. Chronic wound infections make up 60 - 80% of all human infectious diseases, and are cause of major concern to global health in view of our aging population and increasing prevalence of diabetes mellitus and obesity.[2] One in 20 elderly people live with chronic wounds resulting from diabetes or poor circulation, especially those confined to a wheelchair or a bed.[3] Chronic wounds in diabetic patients can be especially fatal. Every year, chronic wound infections in diabetics lead to over 70,000 lower-leg amputations in the United States alone, and up to half of these patients die within the first 18 months following the procedure. Of those who survive, half lose their contralateral extremity within 5 years.[4] As an estimated 415 million adults currently have diabetes and this number is projected to increase to 642 million by year 2040, developing treatment and prevention methods for chronic wound and infection is and will continue to be crucial to reduce medical costs and improve human health.[5]

As common as the health problem is, however, current chronic wound treatments are insufficient and too often lead to amputation due to a lack of understanding of the microbiology of these infections or how to eliminate them. Although it was known that microbial infections significantly complicate and delay wound healing processes, recent research suggests that the presence of microbial biofilms, as opposed to free-swimming planktonic bacteria, contribute significantly to the chronicity of a wound. Over 90% of chronic wounds are infected with biofilms, while biofilms are found in only 6% of acute wounds.[6] The protective and hostile nature of these biofilms renders their complete removal from the wound bed of chronic infections extremely difficult.

These findings lead to a series of intriguing questions. Why do biofilms develop in chronic wounds? Is it the environment of the chronic wound that promotes biofilm formation, or is it the development of a biofilm that causes a wound to become chronic? What are the current methods of treatment of biofilm-associated chronic wounds, and what are the characteristics of biofilms that so often render these treatments inadequate to heal the wound? What are other ways in which researchers and medical providers can explore chronic wound treatment?

This investigation of biofilm formation in chronic wounds will place a special focus on the opportunistic pathogen Pseudomonas aeruginosa and diabetes-associated chronic wounds, as these two areas in microbiology have been well-studied and present good models for relationships between biofilm formation and chronicity of wounds. P. aeruginosa is notorious for its tendency to form resilient biofilms and is the most commonly isolated pathogen from chronic wound infections.[7]

Biofilm General Structure and Properties

Figure 2. The biofilm life cycle. Source: Slonczewski & Foster (2014) Microbiology: An Evolving Science; Chapter 4 Bacterial Culture, Growth, and Development.
Figure 3. Pseudomonas aeruginosa biofilm life cycle. Source: Nature.com.
Figure 4. Scanning electron micrographs of Staphylococcus (left) and E. coli (middle) biofilm formations on Foley catheters after insertion. Biofilms can develop and mature to form complex, crystalline structures (right). Source: Kumar, S.S. Pradeep, H.V. Easwer, and A. Maya Nandkumar, “Multiple Drug Resistant Bacterial Biofilms on Implanted Catheters – A Reservoir of Infection,” 2013, Journal of The Association of Physicians of India, 61 (http://www.japi.org/october_2013/03_oa_multiple_drug_resistant.html).


Biofilms Delay Wound Healing

Pathogenic Synergy in Polymicrobial Biofilms

The EPS Matrix: A Mechanical Barrier and Source of Antibiotic Resistance

Using the Host Immune System Against Itself

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

Methods of Identification and Treatment

Mechanical Debridement

Antibiotic Resistance

Quorum Sensing

Biofilm Disrupting Agents

Section 4

Conclusion

References

  1. Assessment Technologies Institute of Nursing Education. “Wound Care: The anatomy and physiology of wound healing.”
  2. Dowd, Scot E., Randall D. Wolcott, Yan Sun, Trevor McKeehan, Ethan Smith, and Daniel Rhoads. “Polymicrobial Nature of Chronic Diabetic Foot Ulcer Biofilm Infections Determined Using Bacterial Tag Encoded FLX Amplicon Pyrosequencing (bTEFAP).” 2008. PLoS ONE 3(10): e3326. DOI: 10.1371/journal.pone.0003326.
  3. Paddock, Catharine. “Bacteria living on skin may affect how wounds heal.” May 2, 2014. Medical News Today.
  4. Watters, Chase, Katrina DeLeon, Urvish Trivedi, John A. Griswold, Mark Lyte, Ken J. Hampel, Matthew J. Wargo, and Kendra P. Rumbaugh. “Pseudomonas aeruginosa biofilms perturb wound resolution and antibiotic tolerance in diabetic mice.” 2013. Medical Microbiology and Immunology 202: 131-141. DOI: 10.1007/s00430-012-0277-7.
  5. “IDF Diabetes Atlas Executive Summary.” 7th edition. 2015. International Diabetes Federation.
  6. Attinger, Christopher, and Randy Wolcott. “Clinically Addressing Biofilm in Chronic Wounds.” 2011. Advances in Wound Care, 1(3): 127-132. DOI: 10.1089/wound.2011.0333.
  7. Watters, Chase, Jake A. Everett, Cecily Haley, Allie Clinton, and Kendra P. Rumbaugh. “Insulin Treatment Modulates the Host Immune System To Enhance Pseudomonas aeruginosa Wound Biofilms.” 2014. Infection and Immunity 82(1): 92-100. DOI: 10.1128/IAI.00651-13.
  8. Bertesteanu, Serban, Stefanos Triaridis, Milan Stankovic, Veronica Lazar, Mariana Carmen Chifiriuc, Mihaela Vlad, and Raluca Grigore. “Polymicrobial wound infections: Pathophysiology and current therapeutic approaches.” 2014. International Journal of Pharmaceutics 463: 119-126. DOI: 10.1016/j.ijpharm.2013.12.012.
  9. Duplantier, Allen J. and Monique L. Van Hoek. “The human cathelicidin antimicrobial peptide LL-37 as a potential treatment for polymicrobial infected wounds.” 2013. Frontiers in Immunology 4(143): 1-14. DOI: 10.3389/fimmu.2013.00143.
  10. Joo, Hwang-Soo and Michael Otto. “Molecular basis of In Vivo Biofilm Formation by Bacterial Pathogens.” 2012. Chemistry & Biology 19: 1503-1513. DOI: 10.1016/j.chembiol/2012.10.022.
  11. Kirketerp-Moller, Karen Zulkowski, and Garth James. “Chronic Wound Colonization, Infection, and Biofilms.” 2011. Biofilm Infections (Chapter 2). DOI: 10.1007/978-1-4419-6084-9_2.
  12. Percival, Steven L., and Philip G. Bowler. “Biofilms and Their Potential Role in Wound Healing.” 2004. Wounds 16(7).
  13. Percival, Steven L., and Philip G. Bowler. “Understanding the effects of bacterial communities and biofilms on wound healing.” 2004. World Wide Wounds.
  14. Tuttle, Marie S., Eliot Mostow, Pranab Mukherjee, Fen Z. Hu, Rachael melton-Kreft, Garth D. Ehrlich, Scot E. Dowd, and Mohmoud A. Ghannoum. “Characterization of Bacterial Communities in Venous Insufficiency Wounds by Use of Conventional Culture and Molecular Diagnostic Methods.” 2011. Journal of Clinical Microbiology 49(11): 3812-3819. DOI: 10.1128/JCM.00847-11.
  15. Wolcott, R., J.W. Costerton, D. Raoult, and S.J. Culter. “The polymicrobial nature of biofilm infection.” 2013. Clinical Microbiology and Infection 19(2): 107-112. DOI: 10.1111/j.1469-0691.2012.04001.x
  16. Zhao, Ge, Marcia L. Usui, Soyeon I. Lippman, Garth A. James, Philip S. Stewart, Philip Fleckman, and John E. Olerud. “Biofilms and Inflammation in Chronic Wounds.” 2013. Advances in Wound Care 2(7): 389-399. DOI: 10.1089/wound.2012.0381.



Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2016, Kenyon College.