The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing
Abstract
1. Introduction
2. Defining the Healthy Skin Microbiome
2.1. Bacteria
2.2. Fungi
2.3. Viruses
2.4. Other Factors Defining the Skin Microbiome
3. The Cutaneous Microbiome: Aberrations in Human Wounds
3.1. Chronic Wounds
3.2. Acute Wounds
4. The Microbiome, Wound Healing and Inflammation: Mechanistic Insight from Model Systems
Effects of Bacterial Colonization on Skin Inflammation and Cutaneous Homeostasis
5. Modulating the Microbiome: Clinical Implications for Wound Healing and Tissue Regeneration
6. Conclusions
Funding
Conflicts of Interest
Abbreviations
AKT/PKB | Protein Kinase B |
AMP | Anti-Microbial Peptide |
CXCL | Chemokine Ligand |
DFU | Diabetic Foot Ulcer |
DNA | Deoxyribonucleic Acid |
DU | Decubitus Ulcer |
EGF ® | Epidermal Growth Factor (Receptor) |
ERK | Extracellular Signal Regulated Kinase |
FOXP3 | Forkhead Box P3 Protein |
GAS | Group A Streptococcus |
hBD | Human Beta Defense Protein |
HPV | Human Papilloma Virus |
IL | Interleukin |
KGF | Keratinocyte Growth Factor |
MAP | Mitogen Activated Pathway |
MAPK | Mitogen Activated Pathway Kinase |
MKK | Mitogen Activated Pathway Kinase Kinase |
MMP | Matrix Metalloproteinase |
MRSA | Methicillin Resistant Staphylococcus aureus |
NF-κβ | Nuclear Factor Kappa Beta |
NOD | Nucleotide-binding oligomerization domain-containing protein |
PI3K | phosphatidylinositol 3-kinase |
rDNA | Ribosomal Deoxyribonucleic Acid |
RegIIIy | Regenerating Islet Derived Protein Gamma |
RNA | Ribonucleic Acid |
Rnase | Ribonuclease |
ROS | Reactive Oxygen Species |
Sag | Superantigen |
SCFA | Short Chain Fatty Acid |
TAK | Transforming Growth Factor (TGF) F β-activated kinase |
TGF | Transforming Growth Factor |
TLR | Toll Like Receptor |
TNF | Tumor Necrosis Factor |
TRAF | Tumor Necrosis Factor (TNF) receptor-associated factor |
TRAP | Target of RNAIII activating protein |
Treg | T regulatory Cell |
VEGF | Vascular Endothelial Growth Factor |
VLU | Venous Leg Ulcer |
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Bacteria | Positive Effects | Negative Effects | Associated Signaling Pathways |
---|---|---|---|
Staphylococcus epidermidis | Stimulates keratinocyte production of host AMPs (hBD3, RNase7) [22,74,75,88] Induces CD8+ T and IL-17A+ T cells [79] Enhances innate barrier immunity and limits pathogen invasion in absence of inflammation [6,74,80,89] | Occasionally pathogenic Implicated in production of biofilms [79,90,91,92,93] | NF-κB [74,76,89] TRAF1 [7] TLR2/CD36/CD14-p38, MAPK [7] EGFR TRAP [70] |
Staphylococcus aureus | At a local level, super antigen production results in less skin inflammation and purulence due to decreased production of exotoxins and neutrophilic chemotactic factors [81] Amplifies innate immune response of skin via production of AMPs (hBD-3, hBD2, LL-37, RNAse7) [78,79] | Usually pathogenic Implicated in production of biofilms and delayed wound healing in chronic wounds [91,92] Super antigen production elicits robust activation of immune system [81] | TRAP [70,94] phosphatidylinositol 3-kinase/AKT NF/kB ERK TLR-2 [9] |
Group A streptococcus (GAS) | Stimulates production of AMPs, promote epithelial differentiation [95] Activates plasminogen which promotes Keratinocyte chemotaxis and potential re-epithelization of wounds [95] | Usually pathogenic Express proteases which prevent neutrophil recruitment [79,96,97] Produces hyaluronidase which allows bacteria migration through host Extracellular matrix [7] Common cause of superficial and deep skin infections i.e., impetigo, erysipelas, cellulitis [6] | NF-κB/p65 [80] |
Pseudomonas aeruginosa | Accelerates epithelialization and neovascularization in acute wounds Suppresses staphylococcal pathogens in polymicrobial wounds [84] | Usually pathogenic Implicated in production of biofilms and delayed wound healing in chronic wounds [90,91,92,93] | Nod2 [87] TAK1/MKK/p38 [85] |
Corynebacterium jeikeium | Manganese acquisition and production of superoxide dismutase result in host epidermal protection from free radical oxygen species (ROS) [5] | Occasionally pathogenic Common cause of nosocomial skin infections [95] | N/A |
Propionibacteria | Production of bacteriocins protect sebaceous ducts from other pathogenic inhabitants [77] induces expression of TLR2 and TLR4 in keratinocytes71 | Occasionally pathogenic Overabundance associated with development of Acne [5] | N/A |
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Johnson, T.R.; Gómez, B.I.; McIntyre, M.K.; Dubick, M.A.; Christy, R.J.; Nicholson, S.E.; Burmeister, D.M. The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing. Int. J. Mol. Sci. 2018, 19, 2699. https://doi.org/10.3390/ijms19092699
Johnson TR, Gómez BI, McIntyre MK, Dubick MA, Christy RJ, Nicholson SE, Burmeister DM. The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing. International Journal of Molecular Sciences. 2018; 19(9):2699. https://doi.org/10.3390/ijms19092699
Chicago/Turabian StyleJohnson, Taylor R., Belinda I. Gómez, Matthew K. McIntyre, Michael A. Dubick, Robert J. Christy, Susannah E. Nicholson, and David M. Burmeister. 2018. "The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing" International Journal of Molecular Sciences 19, no. 9: 2699. https://doi.org/10.3390/ijms19092699
APA StyleJohnson, T. R., Gómez, B. I., McIntyre, M. K., Dubick, M. A., Christy, R. J., Nicholson, S. E., & Burmeister, D. M. (2018). The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing. International Journal of Molecular Sciences, 19(9), 2699. https://doi.org/10.3390/ijms19092699