Article
Microbiology
Kirsi Savijoki, Henna Myllymaki, Hanna Luukinen, Lauri Paulamaki, Leena-Maija Vanha-Aho, Aleksandra Svorjova, Ilkka Miettinen, Adyary Fallarero, Teemu O. Ihalainen, Jari Yli-Kauhaluoma, Tuula A. Nyman, Mataleena Parikka
Summary: The study reveals that the nontuberculous Mycobacterium marinum ATCC 927 forms two different types of biofilms with distinct structures and persister cells. The proteomic analysis suggests subtype-dependent mechanisms conferring increased virulence and adaptive potential. The findings highlight the importance of targeting both biofilm subtypes in antimycobacterial treatment therapies.
Article
Biochemistry & Molecular Biology
Manitosh Pandey, Satish Tiwari, Sonia Johri, Bichitra K. Biswal, Chandresh Sharma, Amit Kumar Pandey
Summary: This study characterizes a transcriptional regulatory protein in Mycobacterium tuberculosis and demonstrates its ability to modulate transcription. The protein was purified and its functional viability was characterized using various biochemical and biophysical approaches.
Article
Biochemistry & Molecular Biology
Jasdeep Singh, Neha Quadir, Shubham Vashishtha, Ankan Chakraborty, Anwar Alam, Bishwajit Kundu, Uzair Ahmad, Durai Sundar, Nasreen Z. Ehtesham, Seyed E. Hasnain
Summary: This study combines drug repurposing and polypharmacological targeting to modulate the structure-function of multiple proteins in M. tb, leading to the identification of potential drug candidates that can interfere with the growth and replication of the pathogen, and may serve as scaffolds for future anti-MDR strains of M. tb.
BIOCHEMICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Stefan Kreida, Akihiro Narita, Matthew D. Johnson, Elitza I. Tocheva, Anath Das, Debnath Ghosal, Grant J. Jensen
Summary: The horizontal transfer of oncogenic DNA by Agrobacterium tumefaciens causes crown gall disease in plants. This transfer is mediated by the VirB/D4 type 4 secretion system (T4SS), which assembles an extracellular filament, the T-pilus, and is involved in mating pair formation. A 3 A cryo-EM structure of the T-pilus was obtained, revealing its stoichiometric assembly of VirB2 major pilin and phosphatidylglycerol (PG) phospholipid with 5-start helical symmetry. The T-pilus lumen is positively charged, raising questions about its role in ssDNA transfer.
Article
Microbiology
Feifei Zhao, Yu Feng, Chengcheng Wang, Yi Xie, Dan Zhou, Yuling Xiao, Zhiyong Zong
Summary: We present the complete genome sequence of a Mycobacterium marinum strain isolated from skin tissue of a wound infection. The genome consists of a circular chromosome of 6,393,703 base pairs. Phylogenomic analysis places this strain in cluster I among all M. marinum genomes.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2023)
Article
Respiratory System
Andries J. van Tonder, Huw C. Ellis, Colin P. Churchward, Kartik Kumar, Newara Ramadan, Susan Benson, Julian Parkhill, Miriam F. Moffatt, Michael R. Loebinger, William O. C. Cookson
Summary: This study investigates the transmission potential of Mycobacterium avium complex (MAC) among CF and non-CF patients. The results show possible transmission clusters for MAC species, but few epidemiological links were found. Global transmission clusters of Mycobacterium chimaera were associated with heater-cooler units, but the initial ancestor was already circulating among patients.
EUROPEAN RESPIRATORY JOURNAL
(2023)
Article
Immunology
Kelsey A. Gregg, Yihui Wang, Jason Warfel, Elizabeth Schoenfeld, Ewa Jankowska, John F. Cipollo, Matthew Mayho, Christine Boinett, Deepika Prasad, Timothy J. Brickman, Sandra K. Armstrong, Julian Parkhill, Ricardo Da Silva Antunes, Alessandro Sette, James F. Papin, Roman Wolf, Tod J. Merkel
Summary: Despite high vaccination rates, the United States has experienced a resurgence in reported cases of pertussis after switching to the acellular pertussis vaccine. This study identified B. pertussis antigens recognized by convalescent baboon serum and nasopharyngeal wash and identified genes essential for persistence in the baboon airway. The identified antigens are potential candidates for improving acellular pertussis vaccines.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Jody Phelan, Paula Josefina Gomez-Gonzalez, Nuria Andreu, Yosuke Omae, Licht Toyo-Oka, Hideki Yanai, Reiko Miyahara, Supalert Nedsuwan, Paola Florez de Sessions, Susana Campino, Neneh Sallah, Julian Parkhill, Nat Smittipat, Prasit Palittapongarnpim, Taisei Mushiroda, Michiaki Kubo, Katsushi Tokunaga, Surakameth Mahasirimongkol, Martin L. Hibberd, Taane G. Clark
Summary: This study identified eight genetic interaction points associated with susceptibility to tuberculosis, including human loci DAP and RIMS3, as well as FSTL5. The analysis supports the co-evolution and adaptation between host and pathogen in tuberculosis.
NATURE COMMUNICATIONS
(2023)
Review
Chemistry, Medicinal
Saloni Yadav, Aastha Soni, Omprakash Tanwar, Rajendra Bhadane, Gurdyal S. Besra, Neha Kawathekar
Summary: This review provides an in-depth analysis of the structural requirements for DprE1 inhibitors, including both covalent and non-covalent inhibitors, their binding patterns, and their biological activity data in vitro and in vivo. It also introduces a protein quality score (PQS) and an active-site map of the DprE1 enzyme to aid in the development of new anti-TB drugs.
Article
Multidisciplinary Sciences
Yicheng Gong, Chuancun Wei, Jun Wang, Nengjiang Mu, Qinhong Lu, Chengyao Wu, Ning Yan, Huifang Yang, Yao Zhao, Xiuna Yang, Sudagar S. Gurcha, Natacha Veerapen, Sarah M. Batt, Zhiqiang Hao, Lintai Da, Gurdyal S. Besra, Zihe Rao, Lu Zhang
Summary: Arabinogalactan (AG) is an essential component in mycobacterial species, and AftA is a key enzyme involved in AG biosynthesis. The cryo-EM structure of Mtb AftA reveals its dimeric assembly and the participation of a metal ion in its interaction. Structural analysis and mutagenesis studies provide insights into the priming mechanism catalyzed by AftA in Mtb AG biosynthesis, which can contribute to anti-TB drug discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Nidhi Kedia-Mehta, Marta M. Pisarska, Christina Rollings, Chloe O'Neill, Conor De Barra, Cathriona Foley, Nicole A. W. Wood, Neil Wrigley-Kelly, Natacha Veerapen, Gurdyal Besra, Ronan Bergin, Nicholas Jones, Donal O'Shea, Linda V. Sinclair, Andrew E. Hogan
Summary: In this study, it was found that the activation of MAIT cells leads to increased abundance of MYC, a key metabolic regulator and transcription factor. Two MYC-controlled metabolic pathways, amino acid transport and glycolysis, were found to be necessary for MAIT cell proliferation. The study also showed that MAIT cells from obese individuals have decreased MYC abundance upon activation, resulting in impaired cell proliferation and function.
Article
Microbiology
Dorota Jamrozy, Guduru Gopal Rao, Theresa Feltwell, Theresa Lamagni, Priya Khanna, Androulla Efstratiou, Julian Parkhill, Stephen D. D. Bentley
Summary: This study characterized the population structure of GBS isolates from pregnant women in London and found that the majority of isolates belonged to five main lineages. The study also identified nine serotypes, with III, V, II, and Ia being the most common. Moreover, it revealed associations between maternal ethnicity and GBS population structure.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Christopher Ruis, Thomas P. Peacock, Luis M. Polo, Diego Masone, Maria Soledad Alvarez, Angie S. Hinrichs, Yatish Turakhia, Ye Cheng, Jakob McBroome, Russell Corbett-Detig, Julian Parkhill, R. Andres Floto
Summary: Through mutational spectrum analysis, we found distinct mutational patterns in SARS-CoV-2 variants, with the Omicron variant showing reduced G>T mutations compared to other lineages. The mutational analysis also revealed a strong association of high G>T mutations with replication in the lower respiratory tract. Monitoring mutation rates over time showed early divergence of Omicron from Beta, Gamma, and Delta, while the mutational patterns in Alpha varied with changes in transmission source.
MICROBIAL GENOMICS
(2023)
Review
Genetics & Heredity
Gerry Tonkin-Hill, Jukka Corander, Julian Parkhill
Summary: Horizontal gene transfer (HGT) and patterns of gene gain and loss are essential in bacterial evolution. Understanding these patterns can shed light on selection's role in the evolution of bacterial pangenomes and bacterial adaptation to new niches. However, predicting gene presence or absence can be prone to errors, which can complicate the study of HGT dynamics. This review discusses the challenges of constructing accurate pangenomes and the potential consequences of errors on downstream analyses, with the goal of improving bacterial pangenome analyses.
MICROBIAL GENOMICS
(2023)
Article
Genetics & Heredity
Jo Dicks, Mohammed-Abbas Fazal, Karen Oliver, Nicholas E. Grayson, Jake D. Turnbull, Evangeline Bane, Edward Burnett, Ana Deheer-Graham, Nancy Holroyd, Dorota Kaushal, Jacqueline Keane, Gemma Langridge, Jane Lomax, Hannah McGregor, Steve Picton, Michael Quail, Deepak Singh, Alan Tracey, Jonas Korlach, Julie E. Russell, Sarah Alexander, Julian Parkhill
Summary: The National Collection of Type Cultures (NCTC) was established in 1920 in the UK to centralize bacterial and fungal strains. It is one of the oldest collections of this kind worldwide, holding about 6000 strains with medical and scientific importance, available for global academic and veterinary institutions. The NCTC3000 project, a collaboration between NCTC, Pacific Biosciences and the Wellcome Sanger Institute, aims to sequence and assemble the genomes of up to 3000 NCTC strains.
MICROBIAL GENOMICS
(2023)
Article
Immunology
Andrew Chancellor, Robert Alan Simmons, Rahul C. Khanolkar, Vladimir Nosi, Aisha Beshirova, Giuliano Berloffa, Rodrigo Colombo, Vijaykumar Karuppiah, Johanne M. Pentier, Vanessa Tubb, Hemza Ghadbane, Richard J. Suckling, Keith Page, Rory M. Crean, Alessandro Vacchini, Corinne De Gregorio, Verena Schaefer, Daniel Constantin, Thomas Gligoris, Angharad Lloyd, Miriam Hock, Velupillai Srikannathasan, Ross A. Robinson, Gurdyal S. Besra, Marc W. Van der Kamp, Lucia Mori, Raffaele Calogero, David K. Cole, Gennaro De Libero, Marco Lepore
Summary: Canonical MAIT TCRs with dual reactivity to microbial and self-antigens can recognize MR1 promiscuously, allowing MAIT cell responses in the absence of microbial infection. MAIT TCRs can also crossreact with self-antigens and perform T-helper-like functions in vitro. The promiscuity of MR1 recognition by a canonical MAIT TCR is associated with unique TCR β-chain features enriched in self-reactive MAIT cells of healthy individuals. These findings suggest a broader role of MAIT cells in immune homeostasis and diseases beyond microbial immunosurveillance.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Katherine A. Abrahams, Sarah M. Batt, Sudagar S. Gurcha, Natacha Veerapen, Ghader Bashiri, Gurdyal S. Besra
Summary: This study identifies an enzyme required for the synthesis of the mycobacterial cell wall as the target of Pretomanid and delamanid, two pro-drugs used for tuberculosis treatment. The findings provide valuable insights into the mechanisms of action and potential clinical applications of these drugs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Christopher Ruis, Aaron Weimann, Gerry Tonkin-Hill, Arun Prasad Pandurangan, Marta Matuszewska, Gemma G. R. Murray, Roger C. Levesque, Tom L. Blundell, R. Andres Floto, Julian Parkhill
Summary: The study reveals that mutagens and defects in DNA repair can generate context-specific mutational signatures in bacteria, similar to the findings in cancer cells. By reconstructing mutational spectra and analyzing bacterial lineages, the researchers identified mutational patterns associated with DNA repair defects and niche-specific mutagens. These mutational signatures were found to be influenced by both bacterial phylogeny and replication niche. The results suggest that mutational spectra can be used to infer transmission routes for bacterial pathogens.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Juan M. Belardinelli, Divya Arora, Charlotte Avanzi, William H. Wheat, Josephine M. Bryant, John S. Spencer, Tom L. Blundell, Julian Parkhill, R. Andres Floto, Mary Jackson
Summary: Functional genomics analysis of Mycobacterium abscessus clinical isolates revealed phoR as one of the genes under strong evolutionary pressure during lung adaptation. This study demonstrated that acidic pH upregulates phoP in M. abscessus and that clinically relevant non-synonymous mutations in PhoR exacerbate this response. PhoR modulates the autoregulation of its cognate response regulator, PhoP, by controlling its dephosphorylation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Microbiology
Susannah J. Salter, Robyn L. Marsh, Julian Parkhill
Summary: This study reports the complete genome sequence of the Ornithobacterium hominis type strain MSHR-COH1 (ATCC TSD-185/NCTC 14317), a bacterial species isolated from the human nasopharynx. Long-read sequencing reveals that the genome is 2,036,909 bp in length, with a GC content of 35.72%.
MICROBIOLOGY RESOURCE ANNOUNCEMENTS
(2023)
