Acidic pH restricts non-tuberculous mycobacteria replication
Author(s)
Lockwood, Parise K
de Carvalho, Luiz Pedro Sorio
Lai, Rachel PJ
Gutierrez, Maximiliano G
Type
Journal Article
Abstract
Non-tuberculous mycobacteria (NTM) are becoming increasingly prevalent in clinical settings with certain environmental species becoming opportunistic in both immunocompetent and immunodeficient hosts. However, the factors that drive this environmental-to-opportunistic switch remain poorly understood. NTM are environmental organisms that commonly thrive in acidic niches. Conversely, in host cells, acidic pH acts as a defence mechanism. Here, we investigated how acidic pH impacts NTM replication both in vitro and in cellulo. A set of 12 NTM, representing both environmental and opportunistic bacteria, was assessed for growth across a pH range of 4.5–8.0 in vitro, revealing that acid tolerance was species specific. Fluorescent NTM reporters were generated and used to track real-time live cell intracellular replication within human macrophages where acid tolerant species in vitro replicated with a higher efficiency in cellulo than acid sensitive NTM. Further neutralisation of the phagosomal pH using bafilomycin A1 (BafA1) led to enhanced intracellular replication and survival of NTM. This study demonstrated that specific environmental adaptations may determine the opportunistic potential of NTM whilst acidic pH within the host serves as a key host defence mechanism to restrict NTM growth.
Date Issued
2026-05-01
Date Acceptance
2026-02-18
Citation
Molecular Microbiology, 2026, 125 (5), pp.375-388
ISSN
0950-382X
Publisher
Wiley
Start Page
375
End Page
388
Journal / Book Title
Molecular Microbiology
Volume
125
Issue
5
Copyright Statement
© 2026 The Author(s). Molecular Microbiology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Date Publish Online
2026-03-08