Oxidative damage and delayed replication allow viable Mycobacterium tuberculosis to go undetected [TnSeq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis
PROVIDER: GSE180792 | GEO | 2021/11/24
REPOSITORIES: GEO
Similar Datasets
Project description:"Viable but non-culturable” (VBNC) states pose challenges for environmental and clinical microbiology, but their biological mechanisms remain obscure. Mycobacterium tuberculosis (Mtb), the leading cause of death from infection until COVID-19, affords a striking example. Mtb can enter into a “differentially detectable” (DD) state associated with phenotypic antimicrobial resistance in which Mtb cells are viable but undetectable as colony-forming units. We found that Mtb cells enter the DD state when they undergo sublethal oxidative stress that damages their DNA, proteins, and lipids, and in addition, their replication is delayed, allowing repair. Mycobacterium bovis and BCG fail to enter the DD state under similar conditions. These findings have implications for TB latency, detection, relapse, treatment monitoring, and development of regimens that overcome phenotypic antimicrobial resistance.
2021-11-24 | GSE180505 | GEO
Project description:“Viable but non-culturable” (VBNC) states pose challenges for environmental and clinical microbiology, but their biological mechanisms remain obscure. Mycobacterium tuberculosis (Mtb), the leading cause of death from infection until COVID-19, affords a striking example. Mtb can enter into a “differentially detectable” (DD) state associated with phenotypic antimicrobial resistance in which Mtb cells are viable but undetectable as colony-forming units. We found that Mtb cells enter the DD state when they undergo sublethal oxidative stress that damages their DNA, proteins, and lipids, and in addition, their replication is delayed, allowing repair. Mycobacterium bovis and BCG fail to enter the DD state under similar conditions. These findings have implications for TB latency, detection, relapse, treatment monitoring, and development of regimens that overcome phenotypic antimicrobial resistance.
2021-11-24 | GSE180658 | GEO
Project description:Characterization of the putative genetic determinants of the VBNC state in a known spore-forming Gram-positive organism Bacillus subtilis 168. The VBNC state was induced under osmotic stress and aminoglycoside treatment. The transcriptome landscape of VBNC cells was compared to the viable, antibiotic sensitive B. subtilis cells and to the viable cells with no antibiotic treatment.
2022-07-02 | GSE207180 | GEO
Project description:The phenomenon of viable but non-culturable (VBNC) referred as a dormant state of non-sporulating bacteria enhancing the survival in adverse environments. To our knowledge, only few studies have been performed on whole genomic expression of V. parahaemolyticus in VBNC state compared with cells in exponential and early stationary phases. Since many VBNC state studies found DNA, RNA and protein degradation, we hypothesise that gene regulation of VBNC cells is highly reduced, down-regulation of gene expression is dominant and only metabolic functions crucial for survival are kept on a sustained basis. In the VBNC state we found 509 significantly induced genes and 309 significantly repressed by more than twofold compared with unstressed phases among 4820 investigated genes (adjusted P-value < 0.05). Furthermore, up-regulation was dominant in most of the non-metabolism functional categories, while five metabolism-related functional categories revealed down-regulation in the VBNC state. To our knowledge, this is the first study of comprehensive transcriptomic analyses of three phases of V. parahaemolyticus RIMD2210633. Although the mechanism of VBNC state is not yet clear, massive regulation of gene expression occurs in the VBNC state compared with expression in unstressed phases and thus, VBNC cells are active cells. VBNC state gene expression was detected in total bacterial RNA of V. parahaemolyticus. Three phases (exponential phase, early stationary phase, and VBNC state) were used in 8 biological replicates. Gene expression in exponential phase and early stationary phase was used for normalization, respectively.
2015-01-28 | E-GEOD-65340 | biostudies-arrayexpress
Project description:Viable but nonculturable (VBNC) organisms have been underestimated and neglected when studying dormant phenotypes. In clinical settings, VBNC cells may contribute to non-apparent infections capable of being reactivated after months or even years, as for the case of Mycobacterium tuberculosis. The lack of specific and reliable methodology prevents the proper characterization of the VBNC state. Ultimately, these organisms pose a public health risk with potential implications in several industries ranging from pharmaceuticals to food industry. Research regarding their induction and resuscitation is of major importance. Bacteria are able to respond to several environmental and physiological oscillations in part via two-component systems (TCSs). BtsS/BtsR and YpdA/YpdB are two TCSs of Escherichia coli that form a pyruvate sensing network. Their role in the VBNC state is explored in this study.
2018-11-23 | PXD009463 | Pride
Project description:Acidovorax citrulli causes bacterial fruit blotch (BFB) disease in cucurbit crops including watermelon and melon. This bacterium can enter the viable but nonculturable (VBNC) state following exposure to copper sulfate. Moreover, copper-induced VBNC A. citrulli cells could be resuscitated by EDTA. In this study, isobaric tag for relative and absolute quantification (iTRAQ) was used to compare protein profiles of VBNC cells, resuscitated cells at different stages and log-phase cells of the A. citrulli model strain AAC00-1.
2019-07-01 | PXD014431 | iProX
Project description:The phenomenon of viable but non-culturable (VBNC) referred as a dormant state of non-sporulating bacteria enhancing the survival in adverse environments. To our knowledge, only few studies have been performed on whole genomic expression of V. parahaemolyticus in VBNC state compared with cells in exponential and early stationary phases. Since many VBNC state studies found DNA, RNA and protein degradation, we hypothesise that gene regulation of VBNC cells is highly reduced, down-regulation of gene expression is dominant and only metabolic functions crucial for survival are kept on a sustained basis. In the VBNC state we found 509 significantly induced genes and 309 significantly repressed by more than twofold compared with unstressed phases among 4820 investigated genes (adjusted P-value < 0.05). Furthermore, up-regulation was dominant in most of the non-metabolism functional categories, while five metabolism-related functional categories revealed down-regulation in the VBNC state. To our knowledge, this is the first study of comprehensive transcriptomic analyses of three phases of V. parahaemolyticus RIMD2210633. Although the mechanism of VBNC state is not yet clear, massive regulation of gene expression occurs in the VBNC state compared with expression in unstressed phases and thus, VBNC cells are active cells.
2015-01-28 | GSE65340 | GEO
Project description:Introduction: Tuberculosis (TB) is a serious human disease caused by the bacterium Mycobacterium tuberculosis (Mtb). One third of the worldâs population is estimated to be latently infected with Mtb. Exact mechanisms and properties of latent TB infection (LTBI) are not fully elucidated. In essence, the pathogen can enter a dormant or latent state characterized by limited growth and metabolism, resulting in absence of clinical symptoms in the host, and most importantly by increased phenotypic tolerance to the commonly used medications, thereby allowing indefinite persistence in the human body. This persistence is the main reason why the current treatment of new-onset pulmonary TB is very long, consisting of a six months therapy of four antibiotics (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months). Current state of the art: To fight TB globally and more efficiently, it is essential to shorten the treatment for TB with new drugs that are efficient also against LTBI. To facilitate discovery of such drugs, in vitro models for LTBI can be used for high throughput screening of chemical libraries. Current in vitro models such as nutrient starvation (Betts et al. 2002), nutrient depletion (Hampshire et al. 2004; Rifat, Bishai, and Karakousis 2009), progressive hypoxia (Wayne and Hayes 1996), nitric oxide treatment (Martin I. Voskuil et al. 2003) and multiple stress (Deb et al. 2009) mimic the dormant state of Mtb, but the technical settings and equipment required for these models obstruct high throughput applications. Proposed model: The streptomycin (STR)-starved 18b model (SS18b) is a simple and drug discovery efficient Mtb latency model successfully applicable to both in vitro and in vivo settings (Zhang et al. 2012). It is based on the Mtb strain 18b, which is a STR-dependent mutant that enters a viable but nonreplicating state in the absence of STR (Hashimoto 1955). Despite the successful model, we know very little about 18b. How well does SS18b mimic the bacterial response to the complex host-pathogen interactions underlying LTBI, and how does the SS18b response compare to that of other dormancy models are still open questions. In this work we analyse the complete genome of 18b and describe the transcriptomic response of 18b to STR depletion. 12 samples were analyzed. Four biological replicates were sampled during the exponential growth phase, in presence of streptomycin. Four biological replicates derived after 2 weeks of streptomycin depletion, and two biological replicates derive after 4 weeks of streptomycin depletion. Two replicates derive from the resubmission of streptomycin after four weeks of depletion.
2016-02-17 | E-GEOD-71066 | biostudies-arrayexpress
Project description:Escherichia coli O157:H7 can cause haemorrhagic colitis and haemolytic uremic syndrome (HUS) in humans. This pathogen has been implicated in large food-borne outbreaks all over the world. By investigating the implicated salted salmon roe, Makino et al. (2000) suggested that E. coli O157:H7 in the viable but nonculturable (VBNC) state should be the culprit of the outbreak in Japan. High pressure CO2 (HPCD), one of the non-thermal pasteurization techniques, is an effective means to inactivate microorganisms. But in the previous study, we have demonstrated for the first time that HPCD could induce E. coli O157:H7 into the VBNC state, which poses a potential health risk to HPCD-treated products. In order to explore the potential formation mechanisms of VBNC E. coli O157:H7 induced by HPCD, the high-throughput Illumina RNA-seq transcriptomic analysis was conducted for E. coli O157:H7 cells treated at 5 MPa and 25 ℃ for 40 min (VBNC cells) and exponential-phase cells (the control). Finally, 97 genes that differentially transcribed between VBNC state and the control were obtained, with 22 genes up-regulated and 75 genes down-regulated in VBNC cells. These differentially expressed genes were classified in a variety of functional categories, including central metabolic processes, gene replication and expression, cell division, general stress response, respiration, membrane biosynthesis and transport and pathogenicity. Based on these differentially expressed genes, we suggest putative formation mechanisms of VBNC cells induced by HPCD. The finding will provide theoretical foundation for restraining the VBNC state formation under HPCD processing.
2016-06-19 | GSE62394 | GEO
Project description:Introduction: Tuberculosis (TB) is a serious human disease caused by the bacterium Mycobacterium tuberculosis (Mtb). One third of the world’s population is estimated to be latently infected with Mtb. Exact mechanisms and properties of latent TB infection (LTBI) are not fully elucidated. In essence, the pathogen can enter a dormant or latent state characterized by limited growth and metabolism, resulting in absence of clinical symptoms in the host, and most importantly by increased phenotypic tolerance to the commonly used medications, thereby allowing indefinite persistence in the human body. This persistence is the main reason why the current treatment of new-onset pulmonary TB is very long, consisting of a six months therapy of four antibiotics (rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months). Current state of the art: To fight TB globally and more efficiently, it is essential to shorten the treatment for TB with new drugs that are efficient also against LTBI. To facilitate discovery of such drugs, in vitro models for LTBI can be used for high throughput screening of chemical libraries. Current in vitro models such as nutrient starvation (Betts et al. 2002), nutrient depletion (Hampshire et al. 2004; Rifat, Bishai, and Karakousis 2009), progressive hypoxia (Wayne and Hayes 1996), nitric oxide treatment (Martin I. Voskuil et al. 2003) and multiple stress (Deb et al. 2009) mimic the dormant state of Mtb, but the technical settings and equipment required for these models obstruct high throughput applications. Proposed model: The streptomycin (STR)-starved 18b model (SS18b) is a simple and drug discovery efficient Mtb latency model successfully applicable to both in vitro and in vivo settings (Zhang et al. 2012). It is based on the Mtb strain 18b, which is a STR-dependent mutant that enters a viable but nonreplicating state in the absence of STR (Hashimoto 1955). Despite the successful model, we know very little about 18b. How well does SS18b mimic the bacterial response to the complex host-pathogen interactions underlying LTBI, and how does the SS18b response compare to that of other dormancy models are still open questions. In this work we analyse the complete genome of 18b and describe the transcriptomic response of 18b to STR depletion.
2016-02-17 | GSE71066 | GEO