Engraftment of staphylococcal strains on human skin can competitively displace native staphylococci
In: Beneficial MicrobesSearch for other papers by C. Feidenhansl in
Current site
Google Scholar
Search for other papers by K. Schweinshaut in
Current site
Google Scholar
Search for other papers by E. Rruci in
Current site
Google Scholar
Search for other papers by M.-T. Nguyen in
Current site
Google Scholar
Search for other papers by A. Poehlein in
Current site
Google Scholar
Search for other papers by H. Brüggemann in
Current site
Google Scholar
Abstract
Topical probiotic formulations containing live bacteria are being explored as treatments for skin disorders such as atopic dermatitis and acne vulgaris. Certain bacterial strains with antimicrobial and/or anti-inflammatory properties show promise as bacterial therapeutics that could improve these conditions and serve as alternatives to antibiotics, which are increasingly compromised by rising antimicrobial resistance. However, little is known about the engraftment efficacy of such bacterial strains or their impact on the native skin microbiome. In this study, we applied two different coagulase-negative staphylococcal strains, one with antimicrobial activity (Staphylococcus epidermidis 2C-5) and one lacking any activity (Staphylococcus hominis H2-S92), on human back skin of 14 healthy volunteers. Engraftment was assessed using strain-specific PCR and three amplicon-based sequencing approaches at 7 and 30 days after application. Microbial profiles shifted modestly, showing a relative increase in staphylococci and a decrease in Cutibacterium spp. S. epidermidis 2C-5 drastically increased from 0.8% pre-application to 46.9% and 12.1% at days 7 and 30, respectively. S. hominis H2-S92 showed a relative rise from 1.4% to 35.8% at day 7, declining to 2.4% by day 30. Interestingly, Staphylococcus capitis relative abundance decreased by 50-60% at the application sites. These findings indicate that both strains can temporarily engraft and competitively displace native staphylococci. S. epidermidis 2C-5 appeared to colonize more effectively, possibly due to its bacteriocin production. Neither strain affected the phylotype composition of Cutibacterium acnes, suggesting lack of reach to sebaceous follicles, C. acnes’ primary niche. This study supports the potential of staphylococcal probiotics for modulating the skin microbiome. While they may be effective for conditions involving staphylococcal dysbiosis, such as atopic dermatitis, they appear less suited for treating disorders like acne vulgaris, which are associated with C. acnes imbalance.
Purchase
Buy instant access (PDF download and unlimited online access):
Institutional Login
Log in with Open Athens, Shibboleth, or your institutional credentials
Personal login
Log in with your brill.com account
-
Ahle, C.M., Stødkilde, K., Poehlein, A., Bömeke, M., Streit, W.R., Wenck, H., Reuter, J.H., Hüpeden, J. and Brüggemann, H., 2022. Interference and co-existence of staphylococci and Cutibacterium acnes within the healthy human skin microbiome. Communications Biology 5: 923. https://doi.org/10.1038/s42003-022-03897-6
-
Alexeyev, O.A. and Jahns, A.C., 2012. Sampling and detection of skin Propionibacterium acnes: current status. Anaerobe 18: 479-483. https://doi.org/10.1016/j.anaerobe.2012.07.001
-
Becker, K., Heilmann, C. and Peters, G., 2014. Coagulase-negative staphylococci. Clinical Microbiology Reviews 27: 870-926. https://doi.org/10.1128/CMR.00109-13
-
Bier, K. and Schittek, B., 2021. Beneficial effects of coagulase-negative Staphylococci on Staphylococcus aureus skin colonization. Experimatal Dermatology 30: 1442-1452. https://doi.org/10.1111/exd.14381
-
Bierbaum, G., Götz, F., Peschel, A., Kupke, T., van de Kamp, M. and Sahl, H.G., 1996. The biosynthesis of the lantibiotics epidermin, gallidermin, Pep5 and epilancin K7. Antonie Van Leeuwenhoek 69: 119-127. https://doi.org/10.1007/BF00399417
-
Bjerre, R.D., Holm, J.B., Palleja, A., Sølberg, J., Skov, L. and Johansen, J.D., 2021. Skin dysbiosis in the microbiome in atopic dermatitis is site-specific and involves bacteria, fungus and virus. BMC Microbiology 21: 256. https://doi.org/10.1186/s12866-021-02302-2
-
Both, A., Huang, J., Qi, M., Lausmann, C., Weißelberg, S., Büttner, H., Lezius, S., Failla, A.V., Christner, M., Stegger, M., Gehrke, T., Baig, S., Citak, M., Alawi, M., Aepfelbacher, M. and Rohde, H., 2021. Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations. PLoS Pathogens 17: e1009304. https://doi.org/10.1371/journal.ppat.1009304.
-
Brüggemann, H., Salar-Vidal, L., Gollnick, H.P.M. and Lood, R., 2021. A Janus-faced bacterium: host-beneficial and – detrimental roles of Cutibacterium acnes. Frontiers in Microbiology 12: 673845. https://doi.org/10.3389/fmicb.2021.673845
-
Byrd, A.L., Belkaid, Y. and Segre, J.A., 2018. The human skin microbiome. Nature Reviews Microbiology 16: 143-155. https://doi.org/10.1038/nrmicro.2017.157
-
Chen, Y.E., Fischbach, M.A. and Belkaid, Y., 2018. Skin microbiota-host interactions. Nature 553: 427-436. https://doi.org/10.1038/nature25177
-
Christensen, G.J.M. and Brüggemann, H., 2014. Bacterial skin commensals and their role as host guardians. Beneficial Microbes 5: 201-215. https://doi.org/10.3920/BM2012.0062
-
Christensen, I.B., Vedel, C., Clausen, M.L., Kjærulff, S., Agner, T. and Nielsen, D.S., 2021. Targeted screening of lactic acid bacteria with antibacterial activity toward Staphylococcus aureus clonal complex type 1 associated with atopic dermatitis. Frontiers in Microbiology 12: 733847. https://doi.org/10.3389/fmicb.2021.733847
-
Conlan, S., Mijares, L.A., Becker, J., Blakesley, R.W., Bouffard, G.G., Brooks, S., Coleman, H., Gupta, J., Gurson, N., Park, M., Schmidt, B., Thomas, P.J., Otto, M., Kong, H.H., Murray, P.R. and Segre, J.A., NISC Comparative Sequencing Program, 2012. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biology 13: R64. https://doi.org/10.1186/gb-2012-13-7-r64
-
Espadinha, D., Sobral, R.G., Mendes, C.I., Méric, G., Sheppard, S.K., Carriço, J.A., de Lencastre, H. and Miragaia, M., 2019. Distinct phenotypic and genomic signatures underlie contrasting pathogenic potential of Staphylococcus epidermidis clonal lineages. Frontiers in Microbiology 10: 1971. https://doi.org/10.3389/fmicb.2019.01971
-
Feidenhansl, C., Lund, M., Poehlein, A., Lood, R., Lomholt, H.B. and Brüggemann, H., 2024. Cutibacterium and Staphylococcus dysbiosis of the skin microbiome in acne and its decline after isotretinoin. JEADV Clinical Practice 3: 1454-1466. https://doi.org/10.1002/jvc2.487
-
Fernández-Fernández, R., Lozano, C., Eguizábal, P., Ruiz-Ripa, L., Martı́nez-Álvarez, S., Abdullahi, I.N., Zarazaga, M. and Torres, C., 2022. Bacteriocin-like inhibitory substances in staphylococci of different origins and species with activity against relevant pathogens. Frontiers in Microbiology 13: 870510. https://doi.org/10.3389/fmicb.2022.870510
-
Götz, F., Perconti, S., Popella, P., Werner, R. and Schlag, M., 2014. Epidermin and gallidermin: Staphylococcal lantibiotics. International Journal of Medical Microbiology 304: 63-71. https://doi.org/10.1016/j.ijmm.2013.08.012
-
Heilbronner, S., Krismer, B., Brötz-Oesterhelt, H. and Peschel, A., 2021. The microbiome-shaping roles of bacteriocins. Nature Reviews Microbiology 19: 726-739. https://doi.org/10.1038/s41579-021-00569-w
-
Jahns, A.C. and Alexeyev, O.A., 2014. Three dimensional distribution of Propionibacterium acnes biofilms in human skin. Experimental Dermatology 23: 687-689. https://doi.org/10.1111/exd.12482
-
Karoglan, A., Paetzold, B., Pereira de Lima, J., Brüggemann, H., Tüting, T., Schanze, D., Güell, M. and Gollnick, H., 2019. Safety and efficacy of topically applied selected Cutibacterium acnes strains over five weeks in patients with acne vulgaris: An open-label, pilot study. Acta Dermato-Venereologica 99: 1253-1257. https://doi.org/10.2340/00015555-3323
-
Lai, Y., Di Nardo, A., Nakatsuji, T., Leichtle, A., Yang, Y., Cogen, A.L., Wu, Z.R., Hooper, L.V., Schmidt, R.R., von Aulock, S., Radek, K.A., Huang, C.M., Ryan, A.F. and Gallo, R.L., 2009. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nature Medicine 15: 1377-1382. https://doi.org/10.1038/nm.2062
-
Månsson, E., Hellmark, B., Sundqvist, M. and Söderquist, B., 2015. Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery. APMIS 123: 589-595. https://doi.org/10.1111/apm.12392
-
Månsson, E., Bech Johannesen, T., Nilsdotter-Augustinsson, Å., Söderquist, B. and Stegger, M., 2021. Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence. Microbial Genomics 7: 000504. https://doi.org/10.1099/mgen.0.000504
-
Megyeri, K., Mándi, Y., Degré, M. and Rosztóczy, I., 2002. Induction of cytokine production by different staphylococcal strains. Cytokine 19: 206-212. https://doi.org/10.1006/cyto.2002.0876
-
Moore, K.W., de Waal Malefyt, R., Coffman, R.L. and O’Garra, A., 2001. Interleukin-10 and the interleukin-10 receptor. Annual Reviews Immunology 19: 683-765. https://doi.org/10.1146/annurev.immunol.19.1.683
-
Nakatsuji, T., Chen, T.H., Butcher, A.M., Trzoss, L.L., Nam, S.J., Shirakawa, K.T., Zhou, W., Oh, J., Otto, M., Fenical, W. and Gallo, R.L., 2018. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Scientific Advances 4: eaao4502. https://doi.org/10.1126/sciadv.aao4502.
-
Nakatsuji, T., Hata, T.R., Tong, Y., Cheng, J.Y., Shafiq, F., Butcher, A.M., Salem, S.S., Brinton, S.L., Rudman Spergel, A.K., Johnson, K., Jepson, B., Calatroni, A., David, G., Ramirez-Gama, M., Taylor, P., Leung, D.Y.M. and Gallo, R.L., 2021. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nature Medicine 27: 700-709. https://doi.org/10.1038/s41591-021-01256-2
-
Nguyen, M.T., Uebele, J., Kumari, N., Nakayama, H., Peter, L., Ticha, O., Woischnig, A.K., Schmaler, M., Khanna, N., Dohmae, N., Lee, B.L., Bekeredjian-Ding, I. and Götz, F., 2017. Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses. Nature Communications 8: 2246. https://doi.org/10.1038/s41467-017-02234-4
-
Nguyen, M.T., Schellerhoff, L.H., Niemann, S., Schaumburg, F. and Herrmann, M., 2022. Quiescence of human monocytes after affinity purification: a novel method apt for monocyte stimulation assays. Biomolecules 12: 395. https://doi.org/10.3390/biom12030395
-
Oh, J., Byrd, A.L., Deming, C., Conlan, S., Kong, H.H. and Segre, J.A., NISC Comparative Sequencing Program, 2014. Biogeography and individuality shape function in the human skin metagenome. Nature 514: 59-64. https://doi.org/10.1038/nature13786
-
Paetzold, B., Willis, J.R., Pereira de Lima, J., Knödlseder, N., Brüggemann, H., Quist, S.R., Gabaldón, T. and Güell, M., 2019. Skin microbiome modulation induced by probiotic solutions. Microbiome 7: 95. https://doi.org/10.1186/s40168-019-0709-3
-
Rendboe, A.K., Johannesen, T.B., Ingham, A.C., Månsson, E., Iversen, S., Baig, S., Edslev, S., Jensen, J.S., Söderquist, B., Andersen, P.S. and Stegger, M., 2020. The epidome – a species-specific approach to assess the population structure and heterogeneity of Staphylococcus epidermidis colonization and infection. BMC Microbiology 20: 362. https://doi.org/10.1186/s12866-020-02041-w
-
Sandiford, S. and Upton, M., 2012. Identification, characterization, and recombinant expression of epidermicin NI01, a novel unmodified bacteriocin produced by Staphylococcus epidermidis that displays potent activity against staphylococci. Antimicrobial Agents and Chemotherapy 56: 1539-1547. https://doi.org/10.1128/AAC.05397-11
-
Severn, M.M., Williams, M.R., Shahbandi, A., Bunch, Z.L., Lyon, L.M., Nguyen, A., Zaramela, L.S., Todd, D.A., Zengler, K., Cech, N.B., Gallo, R.L. and Horswill, A.R., 2022. The ubiquitous human skin commensal Staphylococcus hominis protects against opportunistic pathogens. mBio 13: e0093022. https://doi.org/10.1128/mbio.00930-22
-
Severn, M.M. and Horswill, A.R., 2023. Staphylococcus epidermidis and its dual lifestyle in skin health and infection. Nature Reviews Microbiology 21: 97-111. https://doi.org/10.1038/s41579-022-00780-3
-
Silverberg, J.I., Lio, P.A., Simpson, E.L., Li, C., Brownell, D.R., Gryllos, I., Ng-Cashin, J., Krueger, T., Swaidan, V.R., Bliss, R.L. and Kim, H.D., 2023. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClinicalMedicine 60: 102002. https://doi.org/10.1016/j.eclinm.2023.102002
-
Stacy, A. and Belkaid, Y., 2019. Microbial guardians of skin health. Science 363: 227-228. https://doi.org/10.1126/science.aat4326
-
Torres Salazar, B.O., Dema, T., Schilling, N.A., Janek, D., Bornikoel, J., Berscheid, A., Elsherbini, A.M.A., Krauss, S., Jaag, S.J., Lämmerhofer, M., Li, M., Alqahtani, N., Horsburgh, M.J., Weber, T., Beltrán-Beleña, J.M., Brötz-Oesterhelt, H., Grond, S., Krismer, B. and Peschel, A., 2024. Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus. Nature Microbiology 9: 200-213. https://doi.org/10.1038/s41564-023-01544-2
-
Uberoi, A., McCready-Vangi, A. and Grice, E.A., 2024. The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nature Reviews Microbiology 22: 507-521. https://doi.org/10.1038/s41579-024-01035-z
-
Volz, T., Kaesler, S., Draing, C., Hartung, T., Röcken, M., Skabytska, Y. and Biedermann, T., 2018. Induction of IL-10-balanced immune profiles following exposure to LTA from Staphylococcus epidermidis. Experimental Dermatology 27: 318-326. https://doi.org/10.1111/exd.13540
-
Wang, Y., Kuo, S., Shu, M., Yu, J., Huang, S., Dai, A., Two, A., Gallo, R.L. and Huang, C.M., 2014. Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Applied Microbiology and Biotechnology 98: 411-424. https://doi.org/10.1007/s00253-013-5394-8
-
Zheng, Y., Hunt, R.L., Villaruz, A.E., Fisher, E.L., Liu, R., Liu, Q., Cheung, G.Y.C., Li, M. and Otto, M., 2022. Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe 30: 301-313. https://doi.org/10.1016/j.chom.2022.01.004
Supplementary Materials
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 327 | 327 | 327 |
| Full Text Views | 24 | 24 | 24 |
| PDF Views & Downloads | 55 | 55 | 55 |
Engraftment of staphylococcal strains on human skin can competitively displace native staphylococci
In: Beneficial MicrobesSearch for other papers by C. Feidenhansl in
Current site
Google Scholar
PubMed
Search for other papers by K. Schweinshaut in
Current site
Google Scholar
PubMed
Search for other papers by E. Rruci in
Current site
Google Scholar
PubMed
Search for other papers by M.-T. Nguyen in
Current site
Google Scholar
PubMed
Search for other papers by A. Poehlein in
Current site
Google Scholar
PubMed
Search for other papers by H. Brüggemann in
Current site
Google Scholar
PubMed
Abstract
Topical probiotic formulations containing live bacteria are being explored as treatments for skin disorders such as atopic dermatitis and acne vulgaris. Certain bacterial strains with antimicrobial and/or anti-inflammatory properties show promise as bacterial therapeutics that could improve these conditions and serve as alternatives to antibiotics, which are increasingly compromised by rising antimicrobial resistance. However, little is known about the engraftment efficacy of such bacterial strains or their impact on the native skin microbiome. In this study, we applied two different coagulase-negative staphylococcal strains, one with antimicrobial activity (Staphylococcus epidermidis 2C-5) and one lacking any activity (Staphylococcus hominis H2-S92), on human back skin of 14 healthy volunteers. Engraftment was assessed using strain-specific PCR and three amplicon-based sequencing approaches at 7 and 30 days after application. Microbial profiles shifted modestly, showing a relative increase in staphylococci and a decrease in Cutibacterium spp. S. epidermidis 2C-5 drastically increased from 0.8% pre-application to 46.9% and 12.1% at days 7 and 30, respectively. S. hominis H2-S92 showed a relative rise from 1.4% to 35.8% at day 7, declining to 2.4% by day 30. Interestingly, Staphylococcus capitis relative abundance decreased by 50-60% at the application sites. These findings indicate that both strains can temporarily engraft and competitively displace native staphylococci. S. epidermidis 2C-5 appeared to colonize more effectively, possibly due to its bacteriocin production. Neither strain affected the phylotype composition of Cutibacterium acnes, suggesting lack of reach to sebaceous follicles, C. acnes’ primary niche. This study supports the potential of staphylococcal probiotics for modulating the skin microbiome. While they may be effective for conditions involving staphylococcal dysbiosis, such as atopic dermatitis, they appear less suited for treating disorders like acne vulgaris, which are associated with C. acnes imbalance.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 327 | 327 | 327 |
| Full Text Views | 24 | 24 | 24 |
| PDF Views & Downloads | 55 | 55 | 55 |
