New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a Dormant State

Caño-Muñiz, Santiago; Anthony, Richard; Niemann, Stefan; Alffenaar, Jan‐Willem C.

doi:10.1128/cmr.00060-17

Cited by 64 publications

(47 citation statements)

References 78 publications

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“…Despite being undetected by culture methods, the dead or weakened tubercle bacilli would be identified by molecular diagnostics, which may appear to be important factor affecting the lower recovery rate by liquid culture [ 13 ]. In addition, dormant bacteria represent bacteria in a state of dormancy, which remain viable but do not form colonies directly on culture media [ 14 ]. There is strong evidence that the history of previous treatments against tuberculosis is an effective condition to induce the formulation of dormant bacteria [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

GeneXpert MTB/RIF Outperforms Mycobacterial Culture in Detecting Mycobacterium tuberculosis from Salivary Sputum

Shi

Dong

et al. 2018

BioMed Research International

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GeneXpert MTB/RIF (Xpert) assay has been endorsed for the diagnosis of pulmonary TB due to its high sensitivity and specificity for culture positive TB. There is no doubt that Xpert could not be more sensitive than mycobacterial culture, while the positive rate of Xpert among sputum samples was higher than that of mycobacterial culture in our laboratory. We therefore carried out a prospective study to determine a potential explanation for this unexpected result regarding the clinical use of Xpert. Overall, a total of 558 patients meeting inclusion criteria were enrolled in final analysis between August 2017 and September 2017 in Beijing Chest Hospital. The overall positive rate of Xpert among sputum samples was 45.9% (256/558), which was significantly higher than that of liquid culture (33.4%, 184/558; P < 0.01). The percentage of culture negative result in salivary sputum was significantly higher than that in mucoid sputum [odds ratio (OR): 5.04, 95% confidence interval (95% CI): 2.74–9.28; P < 0.01]. In addition, the TB cases having previous treatment history had a higher proportion of culture negative result than new cases (OR: 4.26, 95% CI: 1.61–11.28; P = 0.01). In conclusion, the results of this study demonstrate that Xpert outperforms mycobacterial culture in detecting MTB from salivary sputum. In addition, the previously treated patients are more likely to yield negative culture results. Our data will provide important hints to formulate an appropriate diagnostic algorithm for pulmonary tuberculosis based on the appearance of sputum samples.

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Section: Discussionmentioning

confidence: 99%

GeneXpert MTB/RIF Outperforms Mycobacterial Culture in Detecting Mycobacterium tuberculosis from Salivary Sputum

Shi

Dong

et al. 2018

BioMed Research International

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“…8,19 Thus, the ability of NO and ROS to cause dormancy through DosR (DevR) activation in Mtb should stimulate further research into this possibility of the microbiome influencing activation of Mtb dormancy. 38,76 Furthermore, the ability of nutrient starvation and hypoxia to cause dormancy reduces autophagy and ROS as these two processes are triggered by or cause nutrient starvation, respectively. 76,77 VapBC, a critical component of the toxin-antitoxin system (TAS) involved in dormancy state activation, is triggered by IFN or hypoxia, which associates VapBC with ROS and autophagy.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

“…38,76 Furthermore, the ability of nutrient starvation and hypoxia to cause dormancy reduces autophagy and ROS as these two processes are triggered by or cause nutrient starvation, respectively. 76,77 VapBC, a critical component of the toxin-antitoxin system (TAS) involved in dormancy state activation, is triggered by IFN or hypoxia, which associates VapBC with ROS and autophagy. 76 The ability of antimicrobials to also induce MazEF, another component of the TAS that activates dormancy, and toxin-antitoxin chaperones in Mtb within macrophages, limits antimicrobial treatment as a potential factor in activating dormancy.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

“…76,77 VapBC, a critical component of the toxin-antitoxin system (TAS) involved in dormancy state activation, is triggered by IFN or hypoxia, which associates VapBC with ROS and autophagy. 76 The ability of antimicrobials to also induce MazEF, another component of the TAS that activates dormancy, and toxin-antitoxin chaperones in Mtb within macrophages, limits antimicrobial treatment as a potential factor in activating dormancy. 76 We thus hypothesize that the microbiome could indirectly activate dormancy in Mtb through NOD1/TLR signaling, ROS, NO, and IFN production, as well as autophagy activation (Figs.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

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Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Sekyere

Maningi

Fourie

2020

Annals of the New York Academy of Sciences

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Increasingly, gut microbiota distortions are being implicated in the pathogenesis of several infectious and noninfectious diseases. Specifically, in the absence of an eubiotic microbiota, mice are more prone to colonization and infection by Mycobacterium tuberculosis (Mtb). In this qualitative analysis, the following were observed: (1) antimicrobials cause long-term gut microbiota perturbations; (2) Mtb causes limited and transient disturbances to the lung-gut microbiota; (3) pathogens (e.g., Helicobacter hepaticus) affect microbiota integrity and reduce resistance to Mtb; (4) dysbiosis depletes bacterial species regulating proper immune functioning, reducing resistance to Mtb; (5) dysregulated immune cells fail to express important pathogen-recognition receptors (e.g., macrophageinducible C-type lectin; MINCLE) and Mtb-killing cytokines (e.g., IFN-γ, TNF-α, and IL-17), with hampered phagocytic capability; (6) autophagy is central to the immune system's clearance of Mtb, control of inflammation, and immunity-microbiome balance; (7) microbiota-produced short-chain fatty acids, which are reduced by dysbiosis, affect immune cells and increase Mtb proliferation; (8) commensal species (e.g., Lactobacillus plantarum) and microbiota metabolites (e.g., indole propionic acid) reduce tuberculosis progression; and (9) fecal transplants mostly restored eubiosis, increased immune resistance to Mtb, restricted dissemination of Mtb, and reduced tuberculosis-associated organ pathologies. Overuse of antimicrobials, as shown in mice, is a risk factor for reactivating latent or treated tuberculosis.

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“…The critical importance of bacterial latency on the epidemiology and treatment of tuberculosis is widely accepted [11]. Lethal infectious diseases as well as transient infections that result in protective immunity require a continuous supply of naive hosts to be maintained in a population.…”

mentioning

confidence: 99%

Pyrazinamide/Pyrazinoic Acid Resistance in Mycobacterium Tuberculosis: Recent Findings and Implications for Improving the Treatment of Tuberculosis

Anthony

Hertog

2018

Russian Journal of Infection and Immunity

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Abstract.Pyrazinamide (PZA) is unique in that it is a component of the first line therapy for drug sensitive tuberculosis and in most current and experimental treatments also for multi drug resistant tuberculosis. Furthermore, PZA has been shown to help to ensure lasting cure and prevent relapse in shorter multi drug regimens. PZA is a prodrug.Mycobacterial tuberculosis(MTB) PncA enzyme activates the anti-mycobacterial prodrug PZA by transforming it into pyrazinoic acid (POA). The majority of clinical PZA resistant isolates contain mutations within thepncAgene and therefore remain sensitive to POA as they no longer activate PZA. Resistance to the active compound POA requires an alternative resistance mechanism andin vitroselected spontaneous MTB POA resistant mutants typically acquire a range of mutations inpanDor mutations in one of a series of genes most of which are associated with the regulation of the bacterial stringent response. Clinically isolated PZA resistant MTB strains resistant to PZA and POA with mutations in any of these genes are unusual. Thus, it is likely the stringent response is critical for MTBin vivoand a damaged stringent response results in at least a reduction in fitness. Various lead compounds that disrupt the MTB stringent response have been identified that might form the basis for drugs with activity against latent mycobacteria with the potential to shorten tuberculosis treatment. Here we discuss the role of latency in the lifecycle of MTB and possible links to the activity PZA with a focus on potential new targets and drugs.

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New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a Dormant State

Cited by 64 publications

References 78 publications

GeneXpert MTB/RIF Outperforms Mycobacterial Culture in Detecting Mycobacterium tuberculosis from Salivary Sputum

GeneXpert MTB/RIF Outperforms Mycobacterial Culture in Detecting Mycobacterium tuberculosis from Salivary Sputum

Mycobacterium tuberculosis, antimicrobials, immunity, and lung–gut microbiota crosstalk: current updates and emerging advances

Pyrazinamide/Pyrazinoic Acid Resistance in Mycobacterium Tuberculosis: Recent Findings and Implications for Improving the Treatment of Tuberculosis

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