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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...

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Autores principales: Qiu, Tong, Luo, Guangping, Jiang, Jinfeng, Ding, Ping, Li, Qintong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
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.
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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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