ArticleNature medicine2008
A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
211 citing papers in PubMed, 1 synthesis or guideline pooled it, 361 citations in OpenAlex.
- Interplay of autophagy and Th1/Th2-mediated macrophage polarization in host-pathogen dynamics.Frontiers in cellular and infection microbiology · 2025Pooled it
- Cycloserine inhibits glutamate decarboxylase fromJournal of enzyme inhibition and medicinal chemistry · 2026Article
- Transcriptional control of asparagine utilization regulates mycobacterial pH-driven adaptation at the host-pathogen crossroads.The Journal of biological chemistry · 2026Article
- Review
- Acidic pH Restricts Non-Tuberculous Mycobacteria Replication.Molecular microbiology · 2026Article
- The Potassium-Uptake Systems, Trk and Kdp, Coordinately Contribute to Growth Regulation and Survival ofInternational journal of molecular sciences · 2026Article
- Cell wall remodeling-dependent morphotype switch inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Non-canonical peptidoglycan cross-linking is essential forbioRxiv : the preprint server for biology · 2026Article
- Article
- Proteomic insights into a M. tuberculosis clinical isolate with an increased propensity to form viable but non-replicating subpopulations during acid stress.Scientific reports · 2026Article
- CRISPRi-mediated silencing of the ABC transporterFrontiers in microbiology · 2026Article
- Discovery of highly potent α-keto ester-based peptidomimetic inhibitors of the Hip1 protease for the treatment ofEuropean journal of medicinal chemistry reports · 2025Article
- Metabolic Tagging Reveals Surface-Associated Lipoproteins in Mycobacteria.ACS infectious diseases · 2025Article
- Pyrazinamide killsbioRxiv : the preprint server for biology · 2025Article
- Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.FEBS letters · 2025Review
- Review
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Article
- Article
- Antitubercular potential and pH-driven mode of action of salicylic acid derivatives.FEBS open bio · 2025Article
151 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Acidification of the phagosome is considered to be a major mechanism used by macrophages against bacteria, including Mycobacterium tuberculosis (Mtb). Mtb blocks phagosome acidification, but interferon-gamma (IFN-gamma) restores acidification and confers antimycobacterial activity. Nonetheless, it remains unclear whether acid kills Mtb, whether the intrabacterial pH of any pathogen falls when it is in the phagosome and whether acid resistance is required for mycobacterial virulence. In vitro at pH 4.5, Mtb survived in a simple buffer and maintained intrabacterial pH. Therefore, Mtb resists phagolysosomal concentrations of acid. Mtb also maintained its intrabacterial pH and survived when phagocytosed by IFN-gamma-activated macrophages. We used transposon mutagenesis to identify genes responsible for Mtb's acid resistance. A strain disrupted in Rv3671c, a previously uncharacterized gene encoding a membrane-associated protein, was sensitive to acid and failed to maintain intrabacterial pH in acid in vitro and in activated macrophages. Growth of the mutant was also severely attenuated in mice. Thus, Mtb is able to resist acid, owing in large part to Rv3671c, and this resistance is essential for virulence. Disruption of Mtb's acid resistance and intrabacterial pH maintenance systems is an attractive target for chemotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.