Article
Immunology
Zhuhua Wu, Qiuchan Tan, Chenchen Zhang, Yuchuan Zhao, Qinghua Liao, Meiling Yu, Liuyue Xu, Jiawen Wang, Hongdi Liang, Haicheng Li, Liang Chen, Xunxun Chen, Wenjing Wei
Summary: This study investigated the microevolutionary mechanism of ethambutol (EMB) resistance in laboratory-induced mono-EMB-resistant Mycobacterium tuberculosis using an integrated genome-methylome-transcriptome-proteome approach. Aberrantly methylated genes associated with EMB resistance were identified, and their methylation differences were found to be negatively correlated with transcription levels in EMB-resistant strains.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Chemistry, Medicinal
Leonardo Aquino Linhares, Aline dos Santos Peixoto, Luanna de Angelis Correia de Sousa, Joao Paulo Lucena Laet, Aline Caroline da Silva Santos, Valeria Rego Alves Pereira, Maria Madileuza Carneiro Neves, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Jennifer de la Vega, Antonio Pereira-Neves, Arturo San Feliciano, Esther Del Olmo, Haiana Charifker Schindler, Lilian Maria Lapa Montenegro
Summary: Tuberculosis remains a major public health problem and the increase in multidrug-resistant variants makes it more difficult to treat and control. This study evaluated new compounds related to dihydrosphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains and characterized their pharmacological activity. Among the compounds analyzed, 11 showed good to moderate activity against sensitive and MDR Mycobacterium tuberculosis, with potential as a prototype substance for further optimization in preclinical studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
M. E. F. A. G. Oliveira, Y. J. A. Silva, L. A. Azevedo, L. A. Linhares, L. M. L. Montenegro, S. Alves Jr, R. V. S. Amorim
Summary: The study investigated the adjuvant effect of chitosan with the drug ethambutol as a compound, demonstrating a promising composite against strains Mtb H37Rv and multidrug resistant tuberculosis. The CS-EMB compound showed increased antibacterial activity and cytotoxicity compared to the isolated EMB, making it a potential therapeutic option for drug-resistant tuberculosis.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nicole Poladian, Davit Orujyan, William Narinyan, Armani K. Oganyan, Inesa Navasardyan, Prathosh Velpuri, Abraham Chorbajian, Vishwanath Venketaraman
Summary: Mycobacterium tuberculosis (M. tb) causes tuberculosis infection in humans globally, especially in immunocompromised populations and areas with limited tuberculosis treatment resources. The interaction between M. tb and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) plays a crucial role in the immune response, where NF-kappa B promotes pro-inflammatory cytokines and assists in maintaining granulomas and controlling bacterial load. Understanding the dynamics of M. tb and NF-kappa B interaction is essential for better comprehension of the immune response and potential therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Aiketaguli Anwaierjiang, Quan Wang, Haican Liu, Chunjie Yin, Miao Xu, Machao Li, Mengwen Liu, Yan Liu, Xiuqin Zhao, Jinbao Liu, Guilian Li, Xiaokaiti Mijiti, Kanglin Wan
Summary: This study investigated the prevalence and molecular characteristics of drug-resistant M. tuberculosis in the southern region of Xinjiang, China, providing valuable information for choosing early detection methods and proper therapy for tuberculosis in this area. The study revealed that Beijing genotype and retreated patients have a higher risk of developing multi-drug resistant tuberculosis.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Multidisciplinary Sciences
Matus Dohal, Vera Dvorakova, Miluse Sperkova, Martina Pinkova, Andrea Spitaleri, Anders Norman, Andrea Maurizio Cabibbe, Erik Michael Rasmussen, Igor Porvaznik, Maria Skerenova, Ivan Solovic, Daniela Maria Cirillo, Juraj Mokry
Summary: The emergence and spread of drug-resistant tuberculosis pose a threat to public health. This study used whole genome sequencing to analyze the diversity, drug resistance mechanisms, and transmission chains of multidrug-resistant tuberculosis strains in the Czech Republic. The majority of drug-resistant strains belonged to the Beijing lineage, with some strains belonging to the Euro-American lineage. Cluster analysis revealed several clusters, with a majority located in the Prague region.
SCIENTIFIC REPORTS
(2022)
Article
Infectious Diseases
Funmilayo Grace Boni, Insaf Hamdi, Liadrine Moukendza Koundi, Yongdong Dai, Kanshan Shrestra, Mohamed Abdellah Abokadoum, Ulrich Aymard Ekomi Moure, Ismail Mohamed Suleiman, Jianping Xie
Summary: Ethambutol is a drug used for the treatment of tuberculosis, but the emergence of drug resistance is a major concern. This study summarizes the genes implicated in ethambutol resistance and the pharmacoproteomic effect of the drug in Mycobacterium tuberculosis. The findings have important implications for the development of novel anti-tuberculosis antibiotics.
MICROBIAL DRUG RESISTANCE
(2023)
Article
Multidisciplinary Sciences
Omar Al-Jourani, Samuel T. Benedict, Jennifer Ross, Abigail J. Layton, Phillip van der Peet, Victoria M. Marando, Nicholas P. Bailey, Tiaan Heunis, Joseph Manion, Francesca Mensitieri, Aaron Franklin, Javier Abellon-Ruiz, Sophia L. Oram, Lauren Parsons, Alan Cartmell, Gareth S. A. Wright, Arnaud Basle, Matthias Trost, Bernard Henrissat, Jose Munoz-Munoz, Robert P. Hirt, Laura L. Kiessling, Andrew L. Lovering, Spencer J. Williams, Elisabeth C. Lowe, Patrick J. Moynihan
Summary: Bacterial enzymes that cleave the d-arabinan core of arabinogalactan have been identified. These enzymes are important for the modification and/or degradation of the cell wall in mycobacteria. The discovery of these enzymes supports future studies on the structure and function of the mycobacterial cell wall.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Nicolas de Oliveira Rossini, Marcio Vinicius Bertacine Dias
Summary: Genetically antimicrobial resistance in Mycobacterium tuberculosis is a critical concern due to the emergence of resistant strains to commonly used drugs. Understanding the mechanisms of action and resistance, as well as the origins of resistant mutations and their impact on bacterial metabolism, is essential for developing effective therapies. This review summarizes recent literature on novel mutations and molecular mechanisms of drug resistance in tuberculosis treatment, with a focus on pyrazinamide resistance involving PanD and resistance-conferring mutations for new drugs like bedaquiline, pretomanid, delamanid, and linezolid.
GENETICS AND MOLECULAR BIOLOGY
(2023)
Article
Microbiology
Martha L. van der Walt, Karen Shean, Piet Becker, Karen H. Keddy, Joey Lancaster
Summary: The study compared treatment outcomes among MDR-TB patients receiving ethambutol, cycloserine, or terizidone as part of a standardized regimen. Results showed higher success rates and lower default rates in patients receiving cycloserine and terizidone, but higher culture conversion rates in those receiving cycloserine. Further investigation is needed to elucidate the differences observed between cycloserine and terizidone.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Immunology
Precious Bwalya, Eddie S. Solo, Joseph Y. Chizimu, Dipti Shrestha, Grace Mbulo, Jeewan Thapa, Chie Nakajima, Yasuhiko Suzuki
Summary: This study investigated embB mutations among MDR-TB isolates in Zambia and found that molecular EMB resistance testing by DNA sequencing can improve detection of EMB resistance. Additionally, a specific pathogen type, CAS1_Kili, was associated with embB mutations and may contribute to transmission. Detailed investigation of transmission hotspot areas for MDR-TB could help optimize control strategies.
Article
Immunology
Yurong Cai, Weifeng Gao, Pu Wang, Gang Zhang, Xiaoping Wang, Lingling Jiang, Jin Zeng, Yujiong Wang, Zhiwei Wu, Yong Li
Summary: This study investigated the differential responses of bovine alveolar macrophages to Mycobacterium tuberculosis and Mycobacterium bovis infection at the protein level. The results revealed different mechanisms used by the macrophages to resist the two pathogens, and identified activated proteins and signaling pathways associated with autophagy, inflammation, and energy metabolism. These findings provide critical insights into TB pathogenesis and potential biomarkers for more effective treatment strategies. The study also supports the hypothesis of cross-species transmission of MTB.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Infectious Diseases
Danila Zimenkov
Summary: Non-tuberculous mycobacteria, particularly Mycobacterium avium complex (MAC), are capable of infecting humans with compromised immune systems. The current treatment options for MAC infections have unsatisfactory outcomes, mainly due to high MIC values for most drugs. Improvement of treatment outcomes requires the validation of microbiological resistance criteria and identification of molecular mechanisms of resistance.
Review
Immunology
Richard M. M. Jones, Kristin N. N. Adams, Hassan E. E. Eldesouky, David R. R. Sherman
Summary: This review focuses on recent research progress and an updated model for the evolution of drug resistance in Mycobacterium tuberculosis (Mtb) and highlights the contribution of drug tolerance and heterogeneity on resistance. It suggests that drug resistance will continue to pose a threat to tuberculosis control as long as drugs are needed, but with technological advancements and careful management of resources, global progress against TB can still be achieved.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Chemistry, Medicinal
Sukamto S. Mamada, Firzan Nainu, Ayu Masyita, Andri Frediansyah, Rifka Nurul Utami, Mirnawati Salampe, Talha Bin Emran, Clara Mariana Goncalves Lima, Hitesh Chopra, Jesus Simal-Gandara
Summary: This article introduces marine-derived macrolides with promising activity against Mycobacterium tuberculosis, suggests expanding research to in vivo and clinical trials, and explores the potential of in silico studies for screening effective marine macrolides against mycobacterial infections.
Article
Biochemistry & Molecular Biology
Camilla Rodrigues, David Moore, Derrick W. Crook, Daniela M. Cirillo, Philip W. Fowler, Zamin Iqbal, Nazir A. Ismail, Nerges Mistry, Stefan Niemann, Tim E. A. Peto, Guy Thwaites, A. Sarah Walker, Timothy MWalker, Daniel J. Wilson, Sarah G. Earle, Daniel J. Wilson, Clara Grazian, A. Sarah Walker, Martin Hunt, Jeff Knaggs, Zamin Iqbal
Summary: The emergence of drug-resistant tuberculosis is a global health concern. Whole-genome sequencing can uncover new resistance mechanisms. This study identified uncatalogued variants associated with minimum inhibitory concentration and improved our knowledge of antimicrobial resistance in M. tuberculosis.
Article
Microbiology
Nils Wetzstein, Margo Diricks, Thomas A. Kohl, Thomas A. Wichelhaus, Soenke Andres, Laura Paulowski, Carsten Schwarz, Astrid Lewin, Jan Kehrmann, Barbara C. Kahl, Karl Dichtl, Christian Huegel, Olaf Eickmeier, Christina Smaczny, Annika Schmidt, Stefan Zimmermann, Lutz Naehrlich, Sylvia Hafkemeyer, Stefan Niemann, Florian P. Maurer, Michael Hogardt
Summary: This study investigated the epidemiological situation of M. abscessus among CF patients in Germany by performing whole-genome sequencing of isolates. The study identified representatives of all reported DCCs but found no evidence for nosocomial transmission.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Iris Finci, Audrey Albertini, Matthias Merker, Sonke Andres, Nino Bablishvili, Ivan Barilar, Tatiana Caceres, Valeriu Crudu, Eduardo Gotuzzo, Nchimunya Hapeela, Harald Hoffmann, Christine Hoogland, Thomas A. Kohl, Katharina Kranzer, Anna Mantsoki, Florian P. Maurer, Mark P. Nicol, Ecaterina Noroc, Sara Plesnik, Timothy Rodwell, Morten Ruhwald, Theresa Savidge, Max Salfinger, Elizabeth Streicher, Nestani Tukvadze, Robin Warren, Widaad Zemanay, Anna Zurek, Stefan Niemann, Claudia M. Denkinger
Summary: Whole-genome sequencing (WGS) can be used for the diagnosis and management of drug-resistant tuberculosis, and it is correlated with quantitative phenotypic antimicrobial susceptibility testing (AST). The study reveals the potential of WGS for a refined interpretation of resistance and highlights the limitations of our understanding of the genotype and phenotype relationships.
Article
Infectious Diseases
Jabar Babatunde Pacome Achimi Agbo Abdul, Bayode Romeo Adegbite, Micheska Epola Dibamba Ndanga, Jean Ronald Edoa, Rhett Chester Mevyann, Guy Rogue Arnault Ibinda Mfoumbi, Tshisekedi Jean de Dieu, Jocelyn Mahoumbou, Christopher Mebiame Biyogho, Sankarganesh Jeyaraj, Stefan Niemann, Bertrand Lell, Peter Gottfried Kremsner, Abraham Sunday Alabi, Ayola Akim Adegnika, Martin Peter Grobusch
Summary: The increasing incidence of MDR-TB infection in Gabon is alarming, especially among individuals aged 25-35. There is a need for improvement in case finding and contact tracing strategies for treatment-naive MDR-TB patients.
Letter
Public, Environmental & Occupational Health
Jonathan P. Smith, Chawangwa Modongo, John E. Oeltmann, Mbatshi Dima, Ogopotse Matsiri, Othusitse Fane, Tudeutso Molefi, Sanghyuk S. Shin, Ivan Barilar, Stefan Niemann, Nicola M. Zetola, Patrick K. Moonan
AMERICAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Multidisciplinary Sciences
Elize Pietersen, Kim Anderson, Helen Cox, Keertan Dheda, Aihua Bian, Bryan E. Shepherd, Timothy R. Sterling, Robin M. Warren, Yuri F. van der Heijden
Summary: This study found that incomplete treatment with certain anti-TB drugs, such as second-line injectables and para-aminosalicylic acid (PAS), was more common than with other drugs in the treatment of drug-resistant tuberculosis. The reasons for discontinuation varied, with adverse events being the main cause for discontinuation of second-line injectables and patient refusal for discontinuation of PAS.
Article
Cardiac & Cardiovascular Systems
Roland Diel, Karen Meywald-Walter, Christian Schwarzbach, Klaas Voss, Viola Dreyer, Stefan Niemann
Summary: A prospective molecular-epidemiologic study in Hamburg, Germany, evaluated the transmission risk of Mycobacterium tuberculosis complex (Mtbc) by children <15 years in a low-incidence setting. The study found that children with pulmonary TB disease, especially those aged below 10 years, rarely transmit Mtbc to their close contacts in a low-incidence setting.
RESPIRATORY MEDICINE
(2023)
Article
Microbiology
Michaela Zwyer, Liliana Rutaihwa, Etthel Windels, Jerry Hella, Fabrizio Menardo, Mohamed Sasamalo, Gregor Sommer, Lena Schmulling, Sonia Borrell, Miriam C. Reinhard, Anna Dotsch, Hellen Hiza, Christoph D. Stritt, George Sikalengo, Lukas Fenner, Bouke De Jong, Midori Kato-Maeda, Levan Jugheli, Joel Ernst, Stefan Niemann, Leila Jeljeli, Marie Ballif, Matthias Egger, Niaina J. Rakotosamimanana, Dorothy Yeboah-Manu, Prince Asare, Bijaya Malla, Horng Yunn Dou, Nicolas Zetola, Robert Wilkinson, Helen Cox, E. Jane Carter, Joachim Gnokoro, Marcel Yotebieng, Eduardo Gotuzzo, Alash'le Abimiku, Anchalee Avihingsanon, Zhi Ming Xu, Jacques Fellay, Damien Portevin, Klaus Reither, Tanja Stadler, Sebastien Gagneux, Daniela Brites
Summary: In Dar es Salaam, Tanzania, the tuberculosis epidemic is dominated by multiple Mycobacterium tuberculosis complex (MTBC) genotypes introduced from different parts of the world. These genotypes differ in transmission rates and infectious period duration, but have similar overall fitness. The high prevalence of the L3.1.1 genotype is attributed to its early introduction and high transmission rate.
Article
Microbiology
Rachel F. Rollo, Giorgia Mori, Timothy A. Hill, Doris Hillemann, Stefan Niemann, Susanne Homolka, David P. Fairlie, Antje Blumenthal
Summary: Shorter and more effective treatment regimens as well as new drugs are urgently needed to reduce the global burden of tuberculosis (TB). This study discovered a new compound called wollamide B1, which has antimycobacterial activity and can synergize with existing TB antibiotics, enhancing their effectiveness. Wollamide B1 also remains effective against drug-resistant TB strains.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Francy J. Perez-Llanos, Viola Dreyer, Ivan Barilar, Christian Utpatel, Thomas A. Kohl, Martha Isabel Murcia, Susanne Homolka, Matthias Merker, Stefan Niemann
Summary: An outbreak of Mycobacterium tuberculosis complex (MTBC) bacteria was identified among the indigenous populations in the Colombian Amazon region. Whole genome sequencing (WGS) was used to analyze the transmission of MTBC strains and it was found that the use of an alternative reference genome and repetitive regions improved the phylogenetic resolution. The study also revealed the presence of multiple clones in some patients, indicating within-host MTBC diversity.
MICROBIOLOGY SPECTRUM
(2023)
Article
Infectious Diseases
Galo A. Goig, Fabrizio Menardo, Zubeida Salaam-Dreyer, Anzaan Dippenaar, Elizabeth M. Streicher, Johnny Daniels, Anja Reuter, Sonia Borrell, Miriam Reinhard, Anna Doetsch, Christian Beisel, Robin M. Warren, Helen Cox, Sebastien Gagneux
Summary: The study found that compensatory evolution is associated with increased transmission of rifampicin-resistant tuberculosis between patients, and the replicative fitness of rifampicin-resistant Mycobacterium tuberculosis measured in an in vitro laboratory setting correlates with bacterial fitness in clinical settings.
Article
Infectious Diseases
Lindsay Sonnenkalb, Joshua James Carter, Andrea Spitaleri, Zamin Iqbal, Martin Hunt, Kerri Marie Malone, Christian Utpatel, Daniela Maria Cirillo, Camilla Rodrigues, Kayzad Soli Nilgiriwala, Philip William Fowler, Matthias Merker, Stefan Niemann
Summary: This study identified genetic variations that confer resistance to bedaquiline and clofazimine, and established a mutation catalogue using experimental evolution, protein modelling, genome sequencing, and phenotypic data analysis. The findings advance the understanding of drug resistance mechanisms in Mycobacterium tuberculosis complex strains and provide important genetic testing evidence for the design of effective treatments.
Article
Microbiology
Raphael Gries, Michael Dal Molin, Jason Chhen, Edeltraud van Gumpel, Viola Dreyer, Stefan Niemann, Jan Rybniker
Summary: Drug-resistant tuberculosis is a global health care threat that requires new and effective treatment options. Two novel cytochrome bc(1) inhibitors (MJ-22 and B6) have been identified as effective in targeting the Mycobacterium tuberculosis respiratory chain in human macrophages. These compounds have shown low mutation frequencies and unique cross-resistance patterns compared to other advanced cytochrome bc(1) inhibitors.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Eyob Abera Mesfin, Matthias Merker, Dereje Beyene, Abreham Tesfaye, Yassir Adam Shuaib, Desalegn Addise, Belay Tessema, Stefan Niemann
Summary: In this study, the performance of a Sanger sequencing approach to predict resistance against anti-tuberculosis drugs was assessed in Ethiopia. The results showed a high agreement between Sanger sequencing and phenotypic drug susceptibility testing, making it a promising complementary measure for routine testing in Ethiopia.
Article
Infectious Diseases
Peter M. Mbelele, Christian Utpatel, Elingarami Sauli, Emmanuel A. Mpolya, Beatrice K. Mutayoba, Ivan Barilar, Viola Dreyer, Matthias Merker, Margaretha L. Sariko, Buliga M. Swema, Blandina T. Mmbaga, Jean Gratz, Kennedy K. Addo, Michel Pletschette, Stefan Niemann, Eric R. Houpt, Stellah G. Mpagama, Scott K. Heysell
Summary: WGS-based drug resistance prediction accurately predicts drug resistance in Mycobacterium tuberculosis complex strains and the absence of second-line drug resistance genes has potential value in guiding treatment regimen design.
JAC-ANTIMICROBIAL RESISTANCE
(2022)
