Transcriptional characterization of the antioxidant response of Mycobacterium tuberculosis in vivo and during adaptation to hypoxia in vitro

Shi, Lanbo; Sohaskey, Charles D.; North, Robert J.; Gennaro, Maria Laura

doi:10.1016/j.tube.2007.08.007

Cited by 20 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This outcome is consistent with our observation that exposure to low levels of H 2 S triggers an antioxidant response evident by upregulation of genes involved in cysteine metabolism (Fig. 5a, b) and antioxidant genes such as sodA and ahpC 49,50 ( Supplementary Fig. 10A), which permit rapid emergence from hypoxia.…”

Section: Role Of H 2 S Duringsupporting

confidence: 92%

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

et al. 2020

View full text Add to dashboard Cite

Hydrogen sulfide (H 2 S) is involved in numerous pathophysiological processes and shares overlapping functions with CO and •NO. However, the importance of host-derived H 2 S in microbial pathogenesis is unknown. Here we show that Mtb-infected mice deficient in the H 2 S-producing enzyme cystathionine β-synthase (CBS) survive longer with reduced organ burden, and that pharmacological inhibition of CBS reduces Mtb bacillary load in mice. Highresolution respirometry, transcriptomics and mass spectrometry establish that H 2 S stimulates Mtb respiration and bioenergetics predominantly via cytochrome bd oxidase, and that H 2 S reverses •NO-mediated inhibition of Mtb respiration. Further, exposure of Mtb to H 2 S regulates genes involved in sulfur and copper metabolism and the Dos regulon. Our results indicate that Mtb exploits host-derived H 2 S to promote growth and disease, and suggest that host-directed therapies targeting H 2 S production may be potentially useful for the management of tuberculosis and other microbial infections.

show abstract

Section: Role Of H 2 S Duringsupporting

confidence: 92%

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Briefly, 25 ml of culture was used to extract RNA upon cell lysis via the TRIzol bead beater method and phenol extraction [35]. RNA concentrations were determined using a Nanodrop 2000 (NanoDrop Technologies).…”

Section: Methodsmentioning

confidence: 99%

“…RNA concentrations were determined using a Nanodrop 2000 (NanoDrop Technologies). RNA was treated with DNase as previously described [35] and reverse-transcribed using the High Capacity RNA-to-cDNA kit (Applied Biosystems) following the manufacturers’ instructions. RT PCR was performed using Power SYBR Green PCR Master Mix (Applied Biosystems), as previously described [35].…”

Section: Methodsmentioning

confidence: 99%

Impact of Hypoxia on Drug Resistance and Growth Characteristics of Mycobacterium tuberculosis Clinical Isolates

Gao

Yang

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Mycobacterium tuberculosis (MTB) is a specific aerobic bacterium, but can survive under hypoxic conditions, such as those in lung cheese necrosis, granulomas, or macrophages. It is not clear whether the drug sensitivity and growth characteristics of MTB under hypoxic conditions are different from those under aerobic conditions. In this study, we examined the drug resistance and growth characteristics of MTB clinical isolates by a large sample of in vitro drug susceptibility tests, using an automatic growth instrument. Under hypoxic conditions, variance in drug resistance was observed in nearly one-third of the MTB strains and was defined as MTB strains with changed drug sensitivity (MTB-CDS). Among these strains, resistance in a considerable proportion of clinical strains was significantly increased, and some strains emerged as multi-drug resistant. Growth test results revealed a high growth rate and large survival number in macrophages under hypoxia in MTB-CDS. According to the results of fluorescence quantitative PCR, the expression of some genes, including RegX3 (involving RIF resistance), Rv0194 (efflux pump gene), four genes related to transcription regulation (KstR, DosR, Rv0081 and WhiB3) and gene related to translation regulation (DATIN), were upregulated significantly under hypoxic conditions compared to that under aerobic conditions (p < 0.05). Thus, we concluded that some MTB clinical isolates can survive under hypoxic conditions and their resistance could change. As for poor clinical outcomes in patients, based on routine drug susceptibility testing, drug susceptibility tests for tuberculosis under hypoxic conditions should also be recommended. However, the detailed mechanisms of the effect of hypoxia on drug sensitivity and growth characteristics of MTB clinical isolates still requires further study.

show abstract

“…Because incomplete inhibition of phagosome maturation may lead to acidic pH, the transcriptional response to an acid environment has been studied in vitro 1 In addition, because it has been postulated that the central caseous necrosis of the tuberculous granuloma, the pathologic hallmark of human infection, results in limitations in both oxygen and nutrients, there have been several investigations of Mtb gene expression during nutrient starvation and hypoxia. Finally, it has been postulated that Mtb is subjected to both reactive nitrogen (RNI) and oxygen intermediates (ROI) in vivo as an antibacterial host mechanism,2 although transcriptional profiling of the nitrosative and oxidative stress responses in the mouse model of chronic infection have not shown up-regulation of detoxification pathways for RNI and ROI 3…”

Section: Introductionmentioning

confidence: 99%

Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model

et al. 2009

View full text Add to dashboard Cite

As previously published, after aerosol infection with Mycobacterium tuberculosis H37Rv, New Zealand white rabbits established infection with active bacillary replication, but later contained disease to a paucibacillary state through an effective adaptive response consistent with latency. Despite the heterogeneity among outbred rabbits, the resistant response was uniform. Immunosuppression resulted in reactivation with increased lung bacillary burden. Using this rabbit model, we isolated bacillary RNA from infected rabbit lungs and assessed transcriptional profiles of bacillary genes using RT-PCR to examine genes differentially regulated during active replication, persistence, steroid-induced reactivation, and post-steroid immune reconstitution. Genes involved in hypoxia response (fdxA), resuscitation promoting factors (rpfB), and DNA repair pathways (Rv2191) may be important in bacillary persistence. Further investigation into these gene pathways is warranted.

show abstract

Transcriptional characterization of the antioxidant response of Mycobacterium tuberculosis in vivo and during adaptation to hypoxia in vitro

Cited by 20 publications

References 47 publications

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis

Impact of Hypoxia on Drug Resistance and Growth Characteristics of Mycobacterium tuberculosis Clinical Isolates

Tuberculosis genes expressed during persistence and reactivation in the resistant rabbit model

Contact Info

Product

Resources

About