Nitrate-nitrite fate and oxygen sensing in dormant Mycobacterium tuberculosis: A bioinorganic approach highlighting the importance of transition metals

Sousa, Eduardo Henrique Silva; Carepo, Marta S. P.; Moura, José J. G.

doi:10.1016/j.ccr.2020.213476

Cited by 11 publications

(2 citation statements)

References 211 publications

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“…MTB is a slow-growing bacterium that requires oxygen and organic compounds to multiply and obtain energy [ 44 , 45 ]. In cases of latent infection, the bacillus is in a state of rest, with limited oxygen, which favors the slow replication or even stops in replication without cells death [ 46 ].…”

Section: Limitations Of Conventional Therapies In Tb Treatmentmentioning

confidence: 99%

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Carnero Canales,

Marquez Cazorla,

Marquez Cazorla

et al. 2024

Bioactive Materials

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Section: Limitations Of Conventional Therapies In Tb Treatmentmentioning

confidence: 99%

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Carnero Canales,

Marquez Cazorla,

Marquez Cazorla

et al. 2024

Bioactive Materials

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“…The role of DosT and DosS as two distinct O 2 sensors in the dormancy pathway of Mtb has received considerable attention and has been extensively discussed in literature [3,4,8]. Some studies suggest that the presence of these two sensors aligns with the Wayne's hypoxia model, which proposes two stages of non-replicating persistence -NRP-1 and NRP-2 [13][14][15][16]. Previous research has reported an O 2 K d value of 26 μM for DosT and a stronger O 2 K d of 3 μM for DosS, indicating that DosT responds to moderate drops in O 2 levels while DosS responds to deeper hypoxia levels [9].…”

mentioning

confidence: 99%

Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation inMycobacterium tuberculosis

Apiche,

Yee,

Damodaran

et al. 2024

Preprint

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DosT and DosS are heme-based kinases involved in sensing and signaling O2tension in the microenvironment ofMycobacterium tuberculosis(Mtb). Under conditions of low O2, they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O2binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1 μM and 0.46±0.08 μM respectively, which are six to eight-fold stronger than what has been widely referred to in literature. Furthermore, stopped-flow kinetic studies reveal association and dissociation rate constants of 0.84 μM-1s-1and 2.8 s-1, respectively for DosT, and 7.2 μM-1s-1and 3.3 s-1, respectively for DosS. Remarkably, these tighter O2binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model ofMtb. This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O2sensors.

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NIR‐II AIE Luminogen‐Based Erythrocyte‐Like Nanoparticles with Granuloma‐Targeting and Self‐Oxygenation Characteristics for Combined Phototherapy of Tuberculosis

Wang,

Li,

Sun

et al. 2024

Advanced Materials

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Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half‐life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all‐in‐one biomimetic therapeutic nanoparticle featured by aggregation‐induced second near‐infrared emission, granuloma‐targeting, and self‐oxygenation is constructed, which can serve for prominent fluorescence imaging‐navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation‐induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle‐treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.

show abstract

Nitrate-nitrite fate and oxygen sensing in dormant Mycobacterium tuberculosis: A bioinorganic approach highlighting the importance of transition metals

Cited by 11 publications

References 211 publications

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Breaking barriers: The potential of nanosystems in antituberculosis therapy

Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation inMycobacterium tuberculosis

NIR‐II AIE Luminogen‐Based Erythrocyte‐Like Nanoparticles with Granuloma‐Targeting and Self‐Oxygenation Characteristics for Combined Phototherapy of Tuberculosis

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