Bartonella henselae detected in malignant melanoma, a preliminary study

Marna E. Ericson; Edward B. Breitschwerdt; Paul Reicherter; Cole Maxwell; Ricardo G. Maggi; Richard G. Melvin; Azar H. Maluki; Julie M. Bradley; Jennifer C. Miller; Glenn E. Simmons; Jamie Dencklau; Keaton Joppru; Jack Peterson; Will Bae; Janet Scanlon; Lynne T. Bemis

doi:10.3390/pathogens10030326

Bartonella henselae detected in malignant melanoma, a preliminary study

Marna E. Ericson, Edward B. Breitschwerdt, Paul Reicherter, Cole Maxwell, Ricardo G. Maggi, Richard G. Melvin, Azar H. Maluki, Julie M. Bradley, Jennifer C. Miller, Glenn E. Simmons, Jamie Dencklau, Keaton Joppru, Jack Peterson, Will Bae, Janet Scanlon, Lynne T. Bemis

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quin-tana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome.

Original language	English (US)
Article number	326
Pages (from-to)	1-15
Number of pages	15
Journal	Pathogens
Volume	10
Issue number	3
DOIs	https://doi.org/10.3390/pathogens10030326
State	Published - Mar 2021

Bibliographical note

Funding Information:
Conflicts of Interest: E.B.B., in conjunction with Sushama Sontakke and North Carolina State University, holds US Patent No. 7,115,385, Media, and Methods for Cultivation of Microorganisms, which was issued 3 October 2006. E.B.B. is a founder, shareholder, and the chief scientific officer for Galaxy Diagnostics, a company that provides diagnostic testing for the detection of Bartonella species and other vector-borne pathogens in animals and human patients. R.G.M. has led research efforts to optimize the BAPGM platform and is the scientific–technical advisor for Galaxy Diagnostics. J.C.M. is the Head of Research and Development at Galaxy Diagnostics. All other authors declare no conflict of interest. Bartonella testing performed at North Carolina State University by R.M. and E.B.B. was supported by the Bartonella/Vector Borne Diseases Research Fund and the State of North Carolina. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

A375 cells
Bartonella henselae
Bartonella spp
Cancer microbiome
Confocal microscopy of thick sections
Melanoma
Melanoma pathobiome
Multi-immunostaining methods
Vector-borne pathogens

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ericson, M. E., Breitschwerdt, E. B., Reicherter, P., Maxwell, C., Maggi, R. G., Melvin, R. G., Maluki, A. H., Bradley, J. M., Miller, J. C., Simmons, G. E., Dencklau, J., Joppru, K., Peterson, J., Bae, W., Scanlon, J., & Bemis, L. T. (2021). Bartonella henselae detected in malignant melanoma, a preliminary study. Pathogens, 10(3), 1-15. Article 326. https://doi.org/10.3390/pathogens10030326

@article{0104eab7565744ea9884aafc9fd1990f,

title = "Bartonella henselae detected in malignant melanoma, a preliminary study",

abstract = "Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quin-tana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria{\textquoteright}s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome.",

keywords = "A375 cells, Bartonella henselae, Bartonella spp, Cancer microbiome, Confocal microscopy of thick sections, Melanoma, Melanoma pathobiome, Multi-immunostaining methods, Vector-borne pathogens",

author = "Ericson, {Marna E.} and Breitschwerdt, {Edward B.} and Paul Reicherter and Cole Maxwell and Maggi, {Ricardo G.} and Melvin, {Richard G.} and Maluki, {Azar H.} and Bradley, {Julie M.} and Miller, {Jennifer C.} and Simmons, {Glenn E.} and Jamie Dencklau and Keaton Joppru and Jack Peterson and Will Bae and Janet Scanlon and Bemis, {Lynne T.}",

note = "Funding Information: Conflicts of Interest: E.B.B., in conjunction with Sushama Sontakke and North Carolina State University, holds US Patent No. 7,115,385, Media, and Methods for Cultivation of Microorganisms, which was issued 3 October 2006. E.B.B. is a founder, shareholder, and the chief scientific officer for Galaxy Diagnostics, a company that provides diagnostic testing for the detection of Bartonella species and other vector-borne pathogens in animals and human patients. R.G.M. has led research efforts to optimize the BAPGM platform and is the scientific–technical advisor for Galaxy Diagnostics. J.C.M. is the Head of Research and Development at Galaxy Diagnostics. All other authors declare no conflict of interest. Bartonella testing performed at North Carolina State University by R.M. and E.B.B. was supported by the Bartonella/Vector Borne Diseases Research Fund and the State of North Carolina. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

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AU - Breitschwerdt, Edward B.

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AU - Maxwell, Cole

AU - Maggi, Ricardo G.

AU - Melvin, Richard G.

AU - Maluki, Azar H.

AU - Bradley, Julie M.

AU - Miller, Jennifer C.

AU - Simmons, Glenn E.

AU - Dencklau, Jamie

AU - Joppru, Keaton

AU - Peterson, Jack

AU - Bae, Will

AU - Scanlon, Janet

AU - Bemis, Lynne T.

N1 - Funding Information: Conflicts of Interest: E.B.B., in conjunction with Sushama Sontakke and North Carolina State University, holds US Patent No. 7,115,385, Media, and Methods for Cultivation of Microorganisms, which was issued 3 October 2006. E.B.B. is a founder, shareholder, and the chief scientific officer for Galaxy Diagnostics, a company that provides diagnostic testing for the detection of Bartonella species and other vector-borne pathogens in animals and human patients. R.G.M. has led research efforts to optimize the BAPGM platform and is the scientific–technical advisor for Galaxy Diagnostics. J.C.M. is the Head of Research and Development at Galaxy Diagnostics. All other authors declare no conflict of interest. Bartonella testing performed at North Carolina State University by R.M. and E.B.B. was supported by the Bartonella/Vector Borne Diseases Research Fund and the State of North Carolina. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/3

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N2 - Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quin-tana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome.

AB - Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quin-tana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria’s association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome.

KW - A375 cells

KW - Bartonella henselae

KW - Bartonella spp

KW - Cancer microbiome

KW - Confocal microscopy of thick sections

KW - Melanoma

KW - Melanoma pathobiome

KW - Multi-immunostaining methods

KW - Vector-borne pathogens

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JO - Pathogens

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ER -

Bartonella henselae detected in malignant melanoma, a preliminary study

Abstract

Bibliographical note

Keywords

UN SDGs

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