Exposure to Actinobacteria resident in water-damaged buildings and resultant immune injury in Chronic Inflammatory Response Syndrome

Main Article Content

Ryan Shoemaker J Meinhardt A Heyman D Lark

Abstract

The indoor air quality literature has expanded to include a wider variety of contaminants responsible for adverse human health effects. The increased use of Next Generation Sequencing (NGS), combined with the advent of transcriptomic assays, has defined specific causation of innate immune activation within this growing list of pathogenic microbes. Here we report the correlation of specific Actinobacteria as shown by NGS, with specific differential gene activation, using a transcriptomic assay (GENIE; Progene Dx, LLC, Bedford, Massachusetts).


The study provides newly described indices of dominance (DI) and prevalence (PI) for exposure to Actinobacteria that have enabled clinicians to develop targeted treatment protocols to improve health issues as shown by reduction of symptoms, restoration of normal proteomics and transcriptomics, and correcting molecular hypometabolism (MHM), upregulation of MAPKs and TGFBR, as part of a chronic inflammatory response syndrome (CIRS), acquired following exposure to the interior environment of a water-damaged building (WDB).


NGS has shown differences in populations of Actinobacteria found in WDB that are paralleled by differences in innate immune responses. Actinobacteria carried on human skin (HH, human habitat), as opposed to dwelling in soils (SH, soil habitat), consistent with prior publications, can now be represented by DI and PI pinpointing of specific areas of WDB requiring remediation.


A review of the literature shows the capability of HH organisms to induce inflammatory processes in skin and systemically. In addition, the rapid expansion of research on extracellular vesicles suggests a reasonable basis for a mechanism by which resident HH initiate a cascade of inflammatory and metabolic events leading to adverse health effects following exposure to Gram-positive organisms, particularly lipophilic Corynebacteria, Cutibacteria and Mycobacteria, all of which contain mycolic acids in their cell walls.


The role of unique structural differences in specific mycolic acids stratifying those Actinobacteria that are inflammatory may become fertile ground for the treatment of HH-associated illnesses, including CIRS. A review of the biology of receptors for TGF beta-1 adds to the importance of preventing the downstream signaling from upregulated TGFBR in illness associated with elevated PI.


 The aim of the paper is to identify distinguishing clinical features, including inflammation and immunoreactivity involving MAPK and TGFBR that are seen in illness associated with indoor exposure to Actinobacteria.

Article Details

How to Cite
SHOEMAKER, Ryan et al. Exposure to Actinobacteria resident in water-damaged buildings and resultant immune injury in Chronic Inflammatory Response Syndrome. Medical Research Archives, [S.l.], v. 9, n. 10, oct. 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2585>. Date accessed: 22 dec. 2024. doi: https://doi.org/10.18103/mra.v9i10.2585.
Section
Research Articles

References

1. Shoemaker R, Neil V, Heyman A, van der Westhuizen M, McMahon S, Lark D. Newer Molecular Methods Bring New Insights into Human- and Building-Health Risk Assessments From Water-Damaged Buildings: Defining Exposure and Reactivity, the Two Sides of Causation of CIRS-WDB Illness. Medical Research Archives 2021; 9(3): 1-36.
2. Shoemaker R, McMahon S, Heyman A, Lark D, van der Westhuizen M, Ryan J. Treatable metabolic and inflammatory abnormalities in Post COVID Syndrome (PCS) define the transcriptomic basis for persistent symptoms: Lessons From CIRS. Medical Review Archives 2021; 9(:1-8).
3. Shoemaker R, Rash J, Simon E. “Sick Building Syndrome in Water Damaged Buildings: Generalization of the Chronic Biotoxin Associated Illness Paradigm to Indoor Toxigenic Fungi. Bioaerosols, Fungi, Bacteria, Mycotoxins and Human Health.” Bioaerosols, Fungi, Bacteria, Mycotoxins and Human Health: Patho-Physiology, Clinical Effects, Exposure Assessment.
4. US GAO 2008 Indoor mold: Better coordination of research on health effects and more consistent guidance would improve Federal efforts.
5. Shoemaker R, Johnson K, Jim L, Berry Y, Dooley M, Ryan J, McMahon S. Diagnostic process for Chronic Inflammatory response Syndrome (CIRS): A consensus statement report of the Consensus Committee of Surviving Mold. Int. Med Rev. 2018, 4(5): 1-47.
6. Adams R, Miletto M, Lindow S, Taylor J, Bruns T. Airborne bacterial communities in residences: similarities and differences with fungi. PLoS One 2014; 9: 3-e91283.
7. Adams R, Bhangar S, Pasut W, Arens E, Taylor J, Lindow S, Nazaroff W, Bruns T. Chamber bioaerosol study: outdoor air and human occupants as sources of indoor airborne microbes. PLoS One 2015; 10: e0128022.
8. Dmitriev S, Vladimirov D, Lashkevich A. A quick guide to small-molecule inhibitors of eukaryotic protein synthesis. Biochemistry 2020; 85: 1389-1421.
9. Tsunematsu Y, Nishimura S, Hattori A, Oishi S, Fuji N, Kakeya H. Isolation, structure elucidation, and total synthesis of tryptopeptins A and B, new TGF-B signaling modulators from Streptomyces sp. Org Letter 2015; 17(2) :258-261.
10. Layre E. Trafficking of mycobacterium tuberculosis envelope components and release within extracellular vesicles: Host-pathogen interactions beyond the wall. Front Immunol 2020; 11: 1230.
11. Brown L, Wolf J, Prados-Rosales R, Casadevall A. Through the wall: extracellular vesicles in gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol 2015; 13: 620-630.
12. Frojd M, Flardh K. Extrusion of extracellular membrane vesicles from hyphal tips of streptomyces venezuelae coupled to cell-wall stress. Microbiology 2019; 165: 1295-1305.
13. Hempel A, Cantlay S, Molle V, Wang S, Naldrett M, Parker J, Richards D, Jung Y, Buttner M, Flardh K. The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces. PNAS 2012; 109: E2371-E2379.
14. Kononen E, Wade W. Actinomycetes and related organisms in human infections. CMR 2015; 28: 419-442.
15. Rintala H. Actinobacteria in indoor environments: exposures and respiratory health effects. Frontiers in Bioscience 2011; S3: 1273-1284.
16. Schafer J, Jackel U, Kampfer P. Analysis of actinobacteria from mould-colonized water damaged building material. Systematic and Applied Microbiology 2010; 33: 260-268
17. Shoemaker R. Metabolism, molecular hypometabolism and inflammation: Complications of proliferative physiology include metabolic acidosis, pulmonary hypertension, T reg cell deficiency, insulin resistance and neuronal injury. Trends Diabetes Metab 2020; 3: 1-15.
18. Suihko M, Priha O, Alakomi H, Thompson P, Malarstig B, Stott R, Richardson M. Detection and molecular characterization of filamentous actinobacteria and thermoactinomycetes present in water-damaged building materials. Indoor Air 2009; 19: 268-277
19. Rojas A, Padidam M, Cress D, Grady W. TGF-B receptor levels regulate the specificity of signaling pathway activation and biological effects of TGF-B. Biochim Biophys Acta 2009; 1793: 1165-1173.
20. Kyra Y, Defourny Y, Smid E, Abee T. Gram-positive bacterial extracellular vesicles and their impact on health and disease. Frontiers in Microbiology 2018; 9: doi: 10.3389/fmicb
21. Ramachandran A, Vizan P, Das D, Chakravarty P, Vogt J, Rogers K, Muller P, Hinck A, Sapkota G, Hill C. TGF-B uses a novel mode of receptor activation to phosphorylate SMAD1/5 and indue epithelial-to-mesenchymal transition. Elife 2018; e31756.
22. Schwartze J, Becker S, Sakkas E, et al., Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-B signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad axis in lung fibroblasts. Journal of Biological Chemistry 2014; 289: 3262-3275.
23. Khalil H, Kanisicak O, Prasad V, Correll R, Fu X, Schips T, Vagnozzi R, Liu R, Huynh T, Lee S, Molkentin J. Fibroblast-specific TGF-B-Smad2/3 signaling underlies cardiac fibrosis. Clin Invest 2017; 127: 3770-3783.
24. Senatorov V, Friedman A, Milikovsky D, et al., Blood-brain barrier dysfunction in aging induces hyperactivation of TGFB signaling and chronic yet reversible neural dysfunction. Sci Transl Med 2019; 11: eaaw8283.
25. Meinhardt, J., Shoemaker, R. (2020). Proteomic biomarkers, NeuroQuant ® data and symptoms of brain neuronal injury in adults with subjective cognitive impairment. Meinhardt, J., DNP thesis. Georgetown University. Washington, DC
26. Yao Y, Chen R, Wang G, Zhang Y, Liu F. Exosomes derived from mesenchymal stem cells reverse EMT via TGF-B1/Smad pathway and promote repair of damaged endometrium. Stem Cell Research & Therapy 2019; 10: 22.
27. Duan D, Derynck R, Transforming growth factor-B (TGF-B)-induced up-regulation of TGF-B receptors at the cell surface amplifies the TGF-B responses. J. Bio Chem 2019; 294: 8490-8504.
28. Tu E, Chia C, Chen W, Zhang D, Park S, Jin W, Wang D, Alegre M, Zhang Y, Sun Y, Chen W. T cell receptor-regulated TGFB type 1 receptor expression determines T cell quiescence and activation. Immunity 2018; 48: 745-759.
29. Bain C, Montgomery J, Scott C, Kel J, Girard-Madoux H, Martens L, Zangerle-Murray, Ober-Blobaum J, Lindenbergh-Kortleve D, Samson J, Henri S, Lawrence T, Saeys Y, Malissen B, Dalod M, Clausen B. TGFBR signaling controls CD103 + CD11b + dendritic cell development in the intestine. Nat Commun 2017; 8: 620.
30. Altonsy M, Kurwa H, Lauzon G, Amrein M, Gerber A, Almishri W, Mydlarski P. Corynebacterium tuberculostearicum, a human skin colonizer, induces the canonical nuclear factor-kB inflammatory signaling pathway in human skin cells. Immun Inflamm Dis 2020; 8: 62-79.
31. Hinic V, Weisser M, Straub C, Frei R, Goldenberger D. Corynebacterium tuberculostearicum: a potentially misidentified and multi-resistant Corynebacterium species isolated from clinical specimens. J Clin Microbiol 2012; 50: 2561-7.
32. Brown S, Laneelle A, Asselineau J, Barksdale L. Description of Corynebacterium tuberculostearicum sp. nov., a leprosy-derived Corynebacterium. Ann Microbiol 1984; 135B: 251-67.
33. Dobinson H, Anderson T, Chambers S, Doogue M, Seaward L, Werno A. Antimicrobial treatment options for granulomatous mastitis caused by Corynebacterium species. Journal of Clinical Microbiology 2015; 53: 2895-2899.
34. Abreu N, Nagalingam N, Song Y, Roediger F, Pletcher S, Goldberg, Lynch S. Sinus microbiome diversity depletion and Corynebacterium tuberculostearicum enrichment mediates rhinosinusitis. Sci Transl Med. 2012; 4: 151ra124.
35. Shimada E, Kataoka H, Miyazawa Y, Yamamoto M, Igarashi T. Lipoproteins of actinomyces viscosus induce inflammatory responses through TLR2 in human gingival epithelial cells and macrophages. Microbes Infect 2012; 14: 916-21.
36. Barksdale L, Kim K. Propionibacterium, Corynebacterium, mycobacterium and lepra bacilli. Acta Leprol 1984; 2: 153-74.
37. Yao T, Han X, Guan T, Zhai C, Liu C, Liu C, Zhu B, Chen L. Exploration of the microbiome community for saliva, skin, and a mixture of both from population living in Guangdong. Int J Legal Med 2021; 135: 63-62.
38. Szemraj M, Kwaszewska A, Pawlak R, Szewczyk E. Macrolide, lincosamide, and streptogramin B resistance in lipophilic corynebacterial inhabiting healthy human skin. Microb Drug Resist 2014; 20: 404-9.
39. Kalcioglu M, Durmaz R, Ari O, Celik S, Karabudak S. Microbiological investigation of samples collected from healthy middle ears during cochlear implant surgery. Diagn Microbiol Infect Dis 2021; 100: 115390.
40. Korthals M, Ege M, Tebbe C, Mutius E, Bauer J. Application of PCR-SSCP for molecular epidemiological studies on the exposure of farm children to bacteria in environmental dust. J Microbiol Methods 2008; 73: 49-56.
41. Kwaszewska A, Brewczynska A, Szewczyk E. Hydrophobicity and biofilm formation of lipophilic skin corynebacteria. Pol J Microbiol 2006; 55: 189-93.
42. Brook I. The microbiology of normal non-inflamed sinuses. Review B-ENT 2016; 12: 297-304.
43. Boeck I, Wittouck S, Martens K, Claes J, Jorissen M, Steelant B, van den Broek M, Seys S, Hellings P, Vanderveken O, Lebeer S. Anterior nares diversity and pathobionts represent sinus microbiome in chronic rhinosinusitis. ASM 2019; 4: e00532-19.
44. Rhee R, Lu J, Bittinger K. Lee J, Mattei L, Sreih A, Chou S, Miner J, Cohen N, Kelly B, Lee H, Grayson P, Collman R, Merkel P. Dynamic changes in the nasal microbiome associated with disease activity in patients with granulomatosis with polyangiitis. Arthritis Rheumatol 2021; doi: 10.1002/art.41723.
45. Gupta S, Rodriquez M. Mycobacterial extracellular vesicles and host pathogen interactions. Pathogens and Diseases 2018; 76: doi: 10.1093/femspd/fty031.
46. Wang J, Wang Y, Tang L, Garcia R. Extracellular vesicles in mycobacterial infections: Their potential as molecule transfer vectors. Frontiers in Immunology 2019; 10: doi: 10.3389/fimmu
47. Brennan P, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem 1995; 64: 29
48. Vysotskii V, Mazurova K, Shmeleva E. Extracellular material of some representatives of the genus Corynebacterium (the electron microscopic aspect). Zh Mikrobiol Epidemiol Immunobiol 1977; 90-5.
49. Gupta S, Rodriquez G. Isolation and characterization of extracellular vesicles produced by iron-limited mycobacteria. J Vis Exp 2019; 31: doi: 10.3791/60.59.
50. Prados-Rosales R, Weinrick B, Pique D, Jacobs W, Casadevall A, Rodriquez G. Role for mycobacterium tuberculosis membrane vesicles in iron acquisition. J Bact 2014; 197: 1250-1256.
51. Cheng Y, Schorey J. Extracellular vesicles deliver mycobacterium RNA to promote host immunity and bacterial killing. EMBO Reports 2019; 21: e44613
52. Tavassol Z, Aziziraftar K, Behrouzi A. Ghazanfari M, Masoumi M, Fatech A, Vaziri F, Siadat S. Evaluation of Mycobacterium kansasii extracellular vesicles role in BALB/c mice immune modulatory. Int J Mycobacteriol 2020; 9: 58-61.
53. Rodriguez G, Prados-Rosales R. Functions and importance of mycobacterial extracellular vesicles. Appl Microbiol Biotechnol 2016; 100: 3887-3892.
54. Schrempf H, Koebsch I, Walter S, Engelhardt H, Meschke H. Extracellular streptomyces vesicles: amphorae for survival and defence. Microbial Biotechnology 2011; 4: 286-299.
55. Schrempf H, Merling P. Extracellular streptomyces lividans vesicles: composition, biogenesis and antimicrobial activity. Microbial Biotechnology 2015; 8: 644-658.
56. Liu Y, Defourny Y, Smid E, Abee T. Gram-positive bacterial extracellular vesicles and their impact on health and disease. Frontiers in Microbiol 2018; 9: doi: 10.3389/fmicb.
57. Briaud P, Carroll R. Extracellular vesicle biogenesis and functions in gram-positive bacteria. Infection and Immunology 2020; 88: e00433-20.
58. Yang J, McDowll A, Seo H, Kim S, Min T, Jee Y, Choi Y, Park H, Pyun B, Kim Y. Diagnostic models for atopic dermatitis based on serum microbial extracellular vesicle metagenomic analysis: A pilot study. AAIr 2020; 12: 792-805.
59. Bergenhenegouwen J, Kraneveld A, Ruttener L, Kettelarij N, Garssen J, Vos A. Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis. PLoS One 2014; (: e89121.
60. Jeon, J, Mok H, Choi Y, Park S, Jo H, Her J, Han J, Kim Y, Kim K, Ban C. Proteomic analysis of extracellular vesicles derived from Propionibacterium acnes. Proteomics Clin Appl. 2017; 11: doi: 10. 1002/prca.201600040.
61. Holland C, Mak T, Zimny-Arndt U, Schmid M, Meyer T, Jungvlut P, Bruggemann H. Proteomic identification of secreted proteins of Propionibacterium acnes. BMC Microbiology 2010; 10: 230.
62. Choi E. Lee H, Bae I, Kim W, Park J, Lee T, Cho E. Propionibacterium acnes-derived extracellular vesicles promote acne-like phenotypes in human epidermis. Journal of Investigative Dermatology 2018; 138: 1371-1379.
63. Jugeau S, Tenaud I, Knol A, Jarrousse V, Quereux G, Khammari A, Dreno B. Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol 2005; 153: 1105-13.
64. Bakry O, Samaka R, Sebike H, Seleti I. Toll-like receptor two and P. acnes: do they trigger initial acne vulgaris lesions? Anal Quant Cytopathol Histpathol 2014; 36: 100-10.
65. Fathy A, Mohamed R, Ismael N, El-Akhras M. Expression of toll-like receptor two on peripheral blood monocytes of patients with inflammatory and noninflammatory acne vulgaris. Egypt J Immunol 2009; 16: 127-34.
66. Erdei L, Bolla B, Bozo R, Tax G, Urban E, Kemeny L, Szabo K. TNIP1 regulates Cutibacterium acnes-induced innate immune functions in epidermal keratinocytes. Frontiers in Immunology 2018; 9: 1-11.
67. Liu X, Miao J, Wang C, Zhou S, Chen S, Ren Q, Hong X, Wang Y, Hou F, Zhou L, Liu Y. Tubule-derived exosomes play a significant role in fibroblast activation and kidney fibrosis. Kidney Int. 2020; 97: 1181-1195.
68. Wu X, Gao Y, Xu L, Dang W, Yan H, Zou D, Zhu Z, Luo L, Tian N, Wang X, Tong Y, Han Z. Exosomes from high glucose-treated glomerular endothelial cells trigger the epithelial-mesenchymal transition and dysfunction of podocytes. Sci Rep 2017; 7: 9371.
69. Lin Y, Zhang F, Lian X, Peng W, Yin C. Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-B1/Smad2 signaling. Cell Mol Biol 2019; 65: 123-126.
70. You X, Guo Y, Liu X, Ma C. Exosomes derived from LPS-stimulated macrophages promote TGF-B1-induced epithelial-mesenchymal transition of human type II alveolar epithelial A549 cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2019; 35: 673-681
71. Lin Y, Zhang F, Lian X, Peng W, Yin C. Mesenchymal stem cell-derived exosomes improve diabetes mellitus-induced myocardial injury and fibrosis via inhibition of TGF-B1/Smad2 signaling. Cell Mol Biol 2019; 65: 123-126.
72. Borges F, Melo S, Ozdemir B, Kato N, Revuelta I, Miller C, Gattone V, LeBleu V, Kalluri R. TGF-B1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Neph 2013; 24: 385-392.
73. Ramachandra L, Qu Y, Lewis C, Cobb B, Takatsu K, Boom W, Dubyak G, Harding C. Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing major histocompatibility complex class II molecules capable of antigen presentation. Infection and Immunity 2010; 78: 5116-5125.
74. Cuesta F, Passalacqua I, Rodor J, Bhushan R, Denby L, Baker A. Extracellular vesicle crosstalk between pulmonary artery smooth muscle cells and endothelium during excessive TGF-B signaling: implications for PAH vascular remodeling. Cell Communication and Signaling 2019; 17: 143
75. Shelke G, Yin Y, Jang S, Lasser C, Wennmalm S, Hoffmann H, Li L, Gho Y, Nilsson J, Lotvall J. Endosomal signaling via exosome surface TGFB-1. Journal of Extracellular Vesicles 2019; 8: 1650458.
76. Hand T, Vujkovic-Cvijin I, Ridaura V, Belkaid Y. Linking the microbiota, chronic disease and the immune system. Trends Endocrinol Metab. 2016; 27: 831-843.
77. Ghoreschi K, Laurence A, Yang X, Belkaid, Y, et.al. Nature 2010; 467: 967-971.
78. Tamoutounour S, Han S, Deckers J, Constantinides M, Belkaid Y, et.al. Keratinocyte-intrinsic MHCII expression controls microbiota-induced Th1 cell responses. PNAS 2019; 116: 23643-23652.
79. Harrison O, Linehan J, Shih H, Bouladoux N, Han S, Belkaid Y, et.al. Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury. Science 2019; 363: doi: 10.1126/science. aat6280.
80. Hurabielle C, Link V, Bouladoux N, Belkaid Y, et.al. Immunity to commensal skin fungi promotes psoriasiform skin inflammation. PNAS 2020; 117: 16465-16474.
81. Ridaura V, Bouladoux N, Claesen J, Chen E, Belkaid Y, et. al., Contextual control of skin immunity and inflammation by Corynebacterium. J. Exp Med 2018; 215: 785-799.
82. Lark D. Mycolic Acid Production in Actinobacteria. Submitted manuscript 2021.