MCC: Automated Mass and Charge Curation at Genome-Scale Applied to C. tuberculostearicum

Background For many years, antibiotics reliably protected mankind against bacterial infections, including the respiratory tract colonizer Corynebacterium tuberculostearicum. However, the spread of antimicrobial resistance necessitates the search for new treatment options, where the microbiota may play a crucial role. One way to investigate the complex nature of bacteria and their interactions with human hosts or microbiota is through genome-scale metabolic models (GEMs). Constructing GEMs is labor-intensive and time-consuming.

Results We introduce the Python package Mass and Charge Curation (MCC), which implements a new automated algorithm to facilitate mass and charge balancing—one of the most time-consuming reconstruction steps. This package manipulates reconstructions by consolidating data from multiple resources and updating the notes-field with relevant changes. It also generates a visual comparison between draft and curated models, ensuring high-quality metabolic reconstructions. Using MCC, we developed a metabolic reconstruction of C. tuberculostearicum strain DSM 44922. The model was improved based on standardization policies, resulting in a functional, well-annotated, high-quality product. We also simulated the organism’s growth in synthetic nasal medium 3 (SNM3).

Conclusions The high-quality model iCTUB2024RM consistently resembles growth behavior under realistic conditions in an artificial human nasal environment, enhancing understanding of C. tuberculostearicum and its potential impact on health and disease. The curation process of this model led to the development of the MCC package, which facilitates the mass and charge balancing of arbitrary flux balance constraints (fbc) models in SBML format.

Availability MCC is freely available via PIP, from https://github.com/draeger-lab/MassChargeCuration/. The model iCTUB2024RM can be obtained as an SBML file wrapped in an OMEX archive from BioModels Database, accession MODEL2407310001.

Importance The rise of antibiotic resistance has made it essential to explore alternative treatments for bacterial infections, particularly those caused by respiratory tract colonizers like Corynebacterium tuberculostearicum. Understanding the metabolic behavior of these bacteria and their interactions with the human host or microbiota is crucial. genome-scale metabolic models (GEMs) are powerful tools for investigating these interactions, but they are time-consuming to build. Our new Python package, Mass and Charge Curation (MCC), automates a crucial step in the GEM reconstruction process-mass and charge balancing-making it more efficient and reliable. By applying this tool, we developed a high-quality, functional metabolic model for C. tuberculostearicum (iCTUB2024RM), which provides deeper insights into the organism’s growth in a simulated human nasal environment. This work offers a foundation for future research into microbial communities and their role in human health.