10 research outputs found

    Rifampicin resistant 'Mycobacterium tuberculosis' in Vietnam, 2020–2022

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    Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam’s two largest cities, Hanoi and Ho Chi Minh city. Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization’s catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3–20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. Conclusions: Drug resistance among most MDR-TB strains in Vietnam’s two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis

    Etudes structurales des systÚmes de sécrétion de type IX et de type II

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    Les protĂ©ines synthĂ©tisĂ©es et sĂ©crĂ©tĂ©es par les bactĂ©ries jouent des rĂŽles importants pour leur survie. Les bactĂ©ries Ă  Gram nĂ©gatif ont dĂ©veloppĂ© des voies de sĂ©crĂ©tion en tant qu'armes principales pour transporter des facteurs de virulence dans l'environnement extracellulaire ou dans des cellules hĂŽte. L'un de ces systĂšmes, le T9SS a Ă©tĂ© principalement Ă©tudiĂ© chez l'agent pathogĂšne oral Porphyromonas gingivalis et chez la bactĂ©rie mobile Flavobacterium johnsoniae. Un autre complexe, le T2SS est le principal dĂ©terminant de la virulence de la bactĂ©rie Pseudomonas aeruginosa, un agent pathogĂšne de la fibrose kystique. Dans le cadre de ma thĂšse, j'ai rĂ©solu la structure atomique de plusieurs composants centraux du T9SS et du T2SS. Concernant le projet T9SS, j'ai essayĂ© de cristalliser le domaine cytoplasmique de GldL de F. johnsoniae. La co-cristallisation de GldL avec des Nbs a Ă©tĂ© rĂ©alisĂ©e sans succĂšs. NĂ©anmoins, les structures cristallines de deux nanobody contre GldL ont Ă©tĂ© rĂ©solues par remplacement molĂ©culaire. De plus, j'ai Ă©galement travaillĂ© sur la protĂ©ine PG1058 de P. gingivalis. J'ai rĂ©solu sa structure par diffraction anomale Ă  la longueur d’onde du selenium. Concernant le projet T2SS, je me suis concentrĂ© sur la partie N-terminale de XcpQ, une sous-unitĂ© de la sĂ©crĂ©tine. J'ai rĂ©solu la structure cristalline de XcpQN012 seul et en complexe avec le nanobody vhh04 Ă  une rĂ©solution de 2,98 Å et de 2,9 Å, respectivement. Enfin, j'ai participĂ© Ă  la dĂ©termination structurale de TssK, un composant de plaque de base du systĂšme de T6SS et dĂ©terminer la structure cristalline d'un nanobody contre le domaine pĂ©riplasmique de PorM.Proteins synthesized and secreted by bacteria serve many important roles in their survival. In particular, Gram-negative bacteria have evolved secretion pathways as the main weapons for transporting virulence factors into target cells or into the extracellular environment. One of these systems, the type IX secretion system (T9SS) or the Por secretion system, has been studied mainly in the oral pathogen Porphyromonas gingivalis and the gliding bacterium Flavobacterium johnsoniae. Another complex, the type II secretion system (T2SS) is the main determinant of the virulence of Pseudomonas aeruginosa, a cystic fibrosis pathogen. In my PhD thesis, I solved the atomic structure of several core components of both T9SS and T2SS.For the T9SS project, I tried to crystallize the cytoplasmic domain of GldL from F. johnsoniae. The co-crystallization of GldL with Nbs was unsuccessfull. The crystal structures of two nanobodies against GldL were solved by molecular replacement. I also worked on the PG1058 protein of P. gingivalis. I obtained crystals of the selenomethionine-derivatized PG1058 OmpA_C-like domain that diffracted up to 1.55 Å, and solved its structure by single-wavelength anomalous diffraction. For the T2SS project, I focused on the N-terminal part of XcpQ, a subunit of the secretin. I solved the crystal structure of XcpQN012 alone and in complex with nanobody vhh04 at a resolution of 2.98 Å and 2.9 Å, respectively. In addition, I also took part in the structural determination of the base plate component TssK of the T6SS and determined the crystal structure of one nanobody (vhh19) against the periplasmic domain of PorM

    Crystal structure of Type IX secretion system PorE C-terminal domain from Porphyromonas gingivalis in complex with a peptidoglycan fragment

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    International audiencePorphyromonas gingivalis, the major human pathogen associated to periodontal diseases, utilizes the Bacteroidetes-specific type IX secretion system (T9SS) to export virulence factors. pore is a periplasmic multi-domain lipoprotein associated to the outer membrane that was recently identified as essential for T9SS function. Little is known on T9SS at the structural level, and in particular its interaction with peptidoglycan. This prompted us to carry out structural studies on pore full length as well as on its four isolated domains. Here we report the crystal structure of the C-terminal OmpA_C-like putative peptidoglycan-binding domain at 1.55 Å resolution. An electron density volume was identified in the protein cleft, making it possible to build a naturally-occurring peptidoglycan fragment. This result suggests that pore interacts with peptidoglycan and that pore could anchor T9SS to the cell wall

    Camelid nanobodies used as crystallization chaperones for different constructs of PorM, a component of the type IX secretion system from Porphyromonas gingivalis

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    International audiencePorM is a membrane protein that is involved in the assembly of the type IX secretion system (T9SS) in Porphyromonas gingivalis, a major bacterial pathogen that is responsible for periodontal disease in humans. In the context of structural studies of PorM to better understand T9SS assembly, four camelid nanobodies were selected, produced and purified, and their specific interaction with the N-terminal or C-terminal part of the periplasmic domain of PorM was investigated. Diffracting crystals were also obtained, and the structures of the four nanobodies were solved by molecular replacement. Furthermore, two nanobodies were used as crystallization chaperones and turned out to be valuable tools in the structure-determination process of the periplasmic domain of PorM

    Type VI secretion TssK baseplate protein exhibits structural similarity with phage receptor-binding proteins and evolved to bind the membrane complex

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    International audienceThe type VI secretion system (T6SS) is a multiprotein machine widespread in Gram-negative bacteria that delivers toxins into both eukaryotic and prokaryotic cells. The mechanism of action of the T6SS is comparable to that of contractile myophages. The T6SS builds a tail-like structure made of an inner tube wrapped by a sheath, assembled under an extended conformation. Contraction of the sheath propels the inner tube towards the target cell. The T6SS tail is assembled on a platform—the baseplate—which is functionally similar to bacteriophage baseplates. In addition, the baseplate docks the tail to a trans-envelope membrane complex that orients the tail towards the target. Here, we report the crystal structure of TssK, a central component of the T6SS baseplate. We show that TssK is composed of three domains, and establish the contribution of each domain to the interaction with TssK partners. Importantly, this study reveals that the N-terminal domain of TssK is structurally homologous to the shoulder domain of phage receptor-binding proteins, and the C-terminal domain binds the membrane complex. We propose that TssK has conserved the domain of attachment to the virion particle but has evolved the reception domain to use the T6SS membrane complex as receptor

    Evaluation of the expression levels of BRAFV600E mRNA in primary tumors of thyroid cancer using an ultrasensitive mutation assay

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    Background The BRAF(V600E) gene encodes for the mutant BRAF(V600E) protein, which triggers downstream oncogenic signaling in thyroid cancer. Since most currently available methods have focused on detecting BRAF(V600E) mutations in tumor DNA, there is limited information about the level of BRAF(V600E) mRNA in primary tumors of thyroid cancer, and the diagnostic relevance of these RNA mutations is not known. Methods Sixty-two patients with thyroid cancer and non-malignant thyroid disease were included in the study. Armed with an ultrasensitive technique for mRNA-based mutation analysis based on a two step RT-qPCR method, we analysed the expression levels of the mutated BRAF(V600E) mRNA in formalin-fixed paraffin-embedded samples of thyroid tissues. Sanger sequencing for detection of BRAF(V600E) DNA was performed in parallel for comparison and normalization of BRAF(V600E) mRNA expression levels. Results The mRNA-based mutation detection assay enables detection of the BRAF(V600E) mRNA transcripts in a 10,000-fold excess of wildtype BRAF counterparts. While BRAF(V600E) mutations could be detected by Sanger sequencing in 13 out of 32 malignant thyroid cancer FFPE tissue samples, the mRNA-based assay detected mutations in additionally 5 cases, improving the detection rate from 40.6 to 56.3%. Furthermore, we observed a surprisingly large, 3-log variability, in the expression level of the BRAF(V600E) mRNA in FFPE samples of thyroid cancer tissue. Conclusions The expression levels of BRAF(V600E) mRNA was characterized in the primary tumors of thyroid cancer using an ultrasensitive mRNA-based mutation assay. Our data inspires further studies on the prognostic and diagnostic relevance of the BRAF(V600E) mRNA levels as a molecular biomarker for the diagnosis and monitoring of various genetic and malignant diseases.Peer reviewe

    Proceedings of the 5th Conference on Language Teaching and Learning

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    This conference proceedings contains articles on the various research ideas of the academic community and practitioners presented at the 5th Conference on Language Teaching and Learning (LTAL-2023). LTAL2023 was organized by the Ho Chi Minh City University of Food Industry, Vietnam on May 7, 2023. Conference Title: 5th Conference on Language Teaching and LearningConference Acronym: LTAL-2023Conference Date: 7 May 2023Conference Location: VietnamConference Organizers: Ho Chi Minh City University of Food Industry, Vietnam. Related Proceedings:  Proceedings of the 4th Conference on Language Teaching and Learnin

    Power Sector Vision Towards 100% Renewable Electricity by 2050 In Greater Mekong Region - Vietnam Report Part A

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    Part A was prepared by Vietnam Sustainable Energy Alliance(VSEA), leading by the Clean Energy and Sustainable Developmentlab (CleanED/USTH), as a technical summary of the full report.Editor in Chief & Technical Editor of the full report: Jean-Philippe DenruyterThe full report has been prepared by Intelligent Energy Systems PtyLtd (IES) and Mekong Economics (MKE) in relation to provisionof services to World Wide Fund for Nature (WWF).Although electricity from renewable resources, primarilyfrom hydro energy, has been increasing in Vietnam inthe last two decades, fossil fuel-based electricity stilldominates the power generation system in the country.The share of power generation capacity from coal andgas was nearly 54% in 2015 . This share is expected to further increase in the coming yearsbased on the official power development plan of Vietnam, despite Vietnamese fossil energyresources being scarce, with its oil and gas reserves likely to be depleted in the few decadesto come . Hence, a necessary question is: could Vietnam be successful in achieving a lowcarbon power system and pursue a low carbon economy in the next few decades? Or willthe country continue its dependence on fossil fuels?The Intelligent Energy Systems Pty Ltd (“IES”) and Mekong Economics (“MKE”) werecommissioned by WWF – Greater Mekong Programme Office (“WWF-GMPO”) toundertake a project called “Power Sector Vision: Alternatives for power generation inthe Greater Mekong Sub-region”. This was to develop scenarios for the power sectorof countries in the Greater Mekong Sub-region (GMS) that are in line with WWF’s GlobalEnergy Vision that outlines a 100% renewable energy supply by 2050. The objectivesof WWF’s energy vision are: (i) contribute to reduction of global greenhouse emissions(reduction by >80% based on1990 levels by 2050); (ii) reduce dependency on unsustainablehydro and nuclear power; (iii) enhance energy access; (iv) take advantage of new technologiesand solutions; (v) enhance power sector planning frameworks: multi-stakeholder participatoryprocess; and (vi) develop enhancements for energy policy frameworks.The purpose of Power Sector Vision report is to provide detailed country-level descriptionsof three scenarios for the power sector of the Socialist Republic of Viet Nam (Viet Nam):‱ Business as Usual (BAU) power generation development path which is based oncurrent power planning practices, current policy objectives.‱ Sustainable Energy Sector (SES) scenario, where measures are taken to maximallydeploy renewable energy and energy efficiency measures to achieve a near-100%renewable energy power sector; and‱ Advanced Sustainable Energy Sector (ASES) scenario, which assumes a more rapidadvancement and deployment of new and renewable technologies as compared to theSES.The scenarios were based on public data, independent assessments of resource potentials,information obtained from published reports and power system modelling of the GMSregion for the period 2015 to 2050

    Evaluation of the Luminex xTAG Respiratory Viral Panel FAST v2 assay for detection of multiple respiratory viral pathogens in nasal and throat swabs in Vietnam [version 1; referees: 2 approved]

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    Background: Acute respiratory infections (ARI) are among the leading causes of hospitalization in children ≀5 years old. Rapid diagnostics of viral pathogens is essential to avoid unnecessary antibiotic treatment, thereby slowing down antibiotic-resistance. We evaluated the diagnostic performance of the Luminex xTAG Respiratory Viral Panel FAST v2 against viral specific PCR as reference assays for ARI in Vietnam. Methods: Four hundred and forty two nose and throat swabs were collected in viral transport medium, and were tested with Luminex xTAG Respiratory Viral Panel FAST v2. Multiplex RT-PCR and single RT-PCR were used as references. Results: Overall, viral pathogens were detected in a total count of 270/294 (91.8%, 95% CI 88.1-94.7) by the Luminex among reference assays, whilst 112/6336 (1.8%, 95% CI, 1.4-2.1) of pathogens were detected by the Luminex, but not by reference assays. Frequency of pathogens detected by Luminex and reference assays was 379 and 292, respectively. The diagnostic yield was 66.7% (295/442, 95%CI 62.1-71.1%) for the Luminex assay and 54.1% (239/442, 95% CI, 49.3-58.8%) for reference assays. The Luminex kit had higher yields for all viruses except influenza B virus, respiratory syncytial virus, and human bocavirus. High agreements between both methods [mean (range): 0.91 (0.83-1.00)] were found for 10/15 viral agents. Conclusions: The Luminex assay is a high throughput multiplex platform for rapid detection of common viral pathogens causing ARI. Although the current high cost may prevent Luminex assays from being widely used, especially in limited resource settings where ARI are felt most, its introduction in clinical diagnostics may help reduce unnecessary use of antibiotic prescription
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