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Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei
Mycobacterium phlei (M. phlei) is an understudied microbe with medical values as an immunomodulating agent. Here, we establish an industrial strain of M. phlei, CUD, and characterize its genomic, metabolic, and immunological profiles. The established strain has been stably passed for more than a dec...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430659/ https://www.ncbi.nlm.nih.gov/pubmed/35727046 http://dx.doi.org/10.1128/spectrum.00070-22 |
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author | Qiu, Tong Luo, Guangping Jiang, Jinfeng Ding, Ping Li, Qintong |
author_facet | Qiu, Tong Luo, Guangping Jiang, Jinfeng Ding, Ping Li, Qintong |
author_sort | Qiu, Tong |
collection | PubMed |
description | Mycobacterium phlei (M. phlei) is an understudied microbe with medical values as an immunomodulating agent. Here, we establish an industrial strain of M. phlei, CUD, and characterize its genomic, metabolic, and immunological profiles. The established strain has been stably passed for more than a decade, indicated by next-generation sequencing of its 5.3 Mb genome. We show that the intramuscular inoculation of heat-inactivated CUD in immunocompetent mice is well tolerated, and can mount immunological responses. Immunophenotyping demonstrates induced innate and adaptive immune responses in peripheral blood, spleen, and inguinal lymph nodes of CUD-treated mice. Using GC-TOF-MS, we find that the metabolomic profiles of different batches are highly concordant. These results demonstrate a highly reproducible production of M. phlei under GMP conditions. IMPORTANCE Heat-inactivated M. phlei demonstrates promising efficacy to treat BCG-unresponsive non-muscle-invasive bladder cancer patients in clinical trials. However, lack of GMP-grade heat-inactivated M. phlei hampers further clinical investigations. Here, we described a GMP-grade, heat-inactivated M. phlei product, and presented initial characterization of its safety and immunomodulating properties. This product will serve as a starting point for further preclinical studies as well as clinical trials such as in combination with immune checkpoint inhibitors to treat bladder cancer. |
format | Online Article Text |
id | pubmed-9430659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-94306592022-09-01 Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei Qiu, Tong Luo, Guangping Jiang, Jinfeng Ding, Ping Li, Qintong Microbiol Spectr Research Article Mycobacterium phlei (M. phlei) is an understudied microbe with medical values as an immunomodulating agent. Here, we establish an industrial strain of M. phlei, CUD, and characterize its genomic, metabolic, and immunological profiles. The established strain has been stably passed for more than a decade, indicated by next-generation sequencing of its 5.3 Mb genome. We show that the intramuscular inoculation of heat-inactivated CUD in immunocompetent mice is well tolerated, and can mount immunological responses. Immunophenotyping demonstrates induced innate and adaptive immune responses in peripheral blood, spleen, and inguinal lymph nodes of CUD-treated mice. Using GC-TOF-MS, we find that the metabolomic profiles of different batches are highly concordant. These results demonstrate a highly reproducible production of M. phlei under GMP conditions. IMPORTANCE Heat-inactivated M. phlei demonstrates promising efficacy to treat BCG-unresponsive non-muscle-invasive bladder cancer patients in clinical trials. However, lack of GMP-grade heat-inactivated M. phlei hampers further clinical investigations. Here, we described a GMP-grade, heat-inactivated M. phlei product, and presented initial characterization of its safety and immunomodulating properties. This product will serve as a starting point for further preclinical studies as well as clinical trials such as in combination with immune checkpoint inhibitors to treat bladder cancer. American Society for Microbiology 2022-06-21 /pmc/articles/PMC9430659/ /pubmed/35727046 http://dx.doi.org/10.1128/spectrum.00070-22 Text en Copyright © 2022 Qiu et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Qiu, Tong Luo, Guangping Jiang, Jinfeng Ding, Ping Li, Qintong Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title | Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title_full | Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title_fullStr | Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title_full_unstemmed | Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title_short | Genomic, Metabolic, and Immunological Characterization of GMP-Grade Mycobacterium phlei |
title_sort | genomic, metabolic, and immunological characterization of gmp-grade mycobacterium phlei |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9430659/ https://www.ncbi.nlm.nih.gov/pubmed/35727046 http://dx.doi.org/10.1128/spectrum.00070-22 |
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