Publications by authors named "Brigitte Gicquel"

Context: Tuberculosis (TB) diagnosis in children remains challenging due to the paucibacillary nature of specimens and the difficulty in obtaining suitable samples. The use of alternative samples like nasopharyngeal aspirate (NPA) and stools, alongside Xpert MTB/RIF testing, offers promising improvements.

Objective: This study aimed to assess the diagnostic performance of the Xpert MTB/RIF test on NPA and stool samples for detecting intrathoracic TB in children from Madagascar, Cameroon, and Ivory Coast.

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The emergence of drug-resistant Mycobacterium tuberculosis strains highlights the need to discover anti-tuberculosis drugs with novel mechanisms of action. Here we discovered a mycobactericidal strategy based on the prodrug activation of selected chemical derivatives classified as nitronaphthofurans (nNFs) mediated by the coordinated action of the sigH and mrx2 genes. The transcription factor SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in M.

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Tuberculosis remains an important cause of morbidity and mortality throughout the world. Notably, an important number of multi drug resistant cases is an increasing concern. This problem points to an urgent need for novel compounds with antimycobacterial properties and to improve existing therapies.

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With the increasing emergence of drug-resistant Mycobacterium tuberculosis strains, new and effective antibiotics against tuberculosis (TB) are urgently needed. However, the high frequency of poorly water-soluble compounds among hits in high-throughput drug screening campaigns is a major obstacle in drug discovery. Moreover, in vivo testing using conventional animal TB models, such as mice, is time consuming and costly, and represents a major bottleneck in lead compound discovery and development.

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Article Synopsis
  • Several new phenanthrolinic analogs of quinolones were created and tested for antibacterial activity against Mycobacterium tuberculosis and other bacteria.
  • Some of these compounds demonstrated strong effectiveness similar to rifampicin, even against drug-resistant strains of M. tuberculosis.
  • The compounds showed low toxicity and potential for further development into new antibiotics, especially for treating fluoroquinolone-resistant bacterial infections.
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BACKGROUND The incidence of tuberculosis (TB) remains high in many countries, including some middle- and high-income countries without financial constraints for diagnosis and treatment. The implementation of an improved algorithm for diagnosis using 2 rapid molecular tests should help reduce the TB burden. MATERIAL AND METHODS Between April 2018 and March 2019, sputum samples from 711 patients suspected of TB in Nanshan, Shenzhen, China, were included in this prospective study.

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Antibiotics are widely used in the treatment of bacterial infections. Although known for their microbicidal activity, antibiotics may also interfere with the host's immune system. Here, we analyzed the effects of bedaquiline (BDQ), an inhibitor of the mycobacterial ATP synthase, on human macrophages.

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Tuberculosis still claims more lives than any other pathogen, and a vaccine better than BCG is urgently needed. One of the challenges for novel TB vaccines is to protect against all Mycobacterium tuberculosis lineages, including the most virulent ones, such as the Beijing lineage. Here we developed a live attenuated M.

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Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M.

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Antibiotics can stimulate or depress gene expression in bacteria. The analysis of transcriptional responses of to antimycobacterial compounds has improved our understanding of the mode of action of various drug classes and the efficacy and effect of such compounds on the global metabolism of . This approach can provide new insights for known antibiotics, for example those currently used for tuberculosis treatment, as well as help to identify the mode of action and predict the targets of new compounds identified by whole-cell screening assays.

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Background: Infectious diseases are still a leading cause of death and, with the emergence of drug resistance, pose a great threat to human health. New drugs and strategies are thus urgently needed to improve treatment efficacy and limit drug-associated side effects. Nanotechnology-based drug delivery systems are promising approaches, offering hope in the fight against drug resistant bacteria.

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Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds.

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Rationale: In addition to their well-known function as antibody-producing cells, B lymphocytes can markedly influence the course of infectious or noninfectious diseases via antibody-independent mechanisms. In tuberculosis (TB), B cells accumulate in lungs, yet their functional contribution to the host response remains poorly understood.

Objectives: To document the role of B cells in TB in an unbiased manner.

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Tuberculosis remains an important cause of morbidity and mortality throughout the world, amplified by the expansion of antibiotic resistance. Increasing active efflux of the antibiotic is one of the several strategies used by bacteria to resist to antibiotics. After showing the importance of the RND superfamily of efflux pumps in drug resistance, this review focuses on the protein MmpL5, a transmembrane transporter of Mycobacterium.

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The objective of this study was to find molecules with anti-mycobacterial activity from a natural compounds library, investigate their mechanisms of resistance, and assess their synergy with antibiotics. We screened a library of 2582 natural compounds with Mycobacterium aurum with the aim of identifying molecules with anti-mycobacterial activity. The hits with the lowest MICs in M.

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Article Synopsis
  • The text discusses a study on a major human pathogen that can survive inside host cells and evade the immune system by inhibiting essential immune responses like phagosome maturation and cytokine production.* -
  • Researchers used a transposon mutant library of a virulent pathogen to identify mutants that activate NF-κB, a crucial immune regulator, revealing that one mutant lacked the ability to produce specific glycolipids known as sulfoglycolipids.* -
  • The study concludes that sulfoglycolipids act as antagonists for Toll-like receptors, specifically interfering with NF-κB activation and cytokine production, thereby showcasing a novel mechanism by which the pathogen undermines the innate immune defense and enhances its virulence.*
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In this study, we aimed to decipher the natural resistance mechanisms of mycobacteria against novel compounds isolated by whole-cell-based high-throughput screening (HTS). We identified active compounds using Mycobacterium aurum. Further analyses were performed to determine the resistance mechanism of M.

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Background: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. The considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. Model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating M.

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In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.

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Multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of pose major problems for global health. The GeneXpert MTB/RIF (Xpert) assay rapidly detects resistance to rifampin (RIF), but for detection of the additional resistance that defines MDR-TB (MDR tuberculosis) and XDR-TB, and for molecular epidemiology, specimen cultures and a biosafe infrastructure are generally required. We sought to determine whether the remnants of sputa prepared for the Xpert assay could be used directly to find mutations associated with drug resistance and to study molecular epidemiology, thus providing precise characterization of MDR-TB cases in countries lacking biosafety level 3 (BSL3) facilities for cultures.

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A long-term study was undertaken to monitor immune responses, faecal cultures and clinical disease in sheep experimentally infected with Mycobacterium avium subspecies paratuberculosis (Map) strain Telford. New Zealand Merino lambs (N=56) were challenged with three oral doses of Map suspension. The lambs were weighed and faecal and blood samples obtained at different time-points.

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The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis-infected human macrophages (ΜΦ).

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Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on PZA resistant (PZA-R) rate in China. From June 2009 to June 2012, we selected 493 isolates from five field settings in China to investigate PZA-R by pncA gene sequencing. The result showed that PZA-R rate was 1.

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