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Role of alanine racemase mutations in Mycobacterium tuberculosis D-cycloserine ...
Nakatani, Yoshio; Opel-Reading, Helen K; Merker, Matthias; Machado, Diana; Andres, Sönke; Kumar, S Siva; Moradigaravand, Danesh; Coll, FrancescCopyright © 2017 Nakatani et al.; A screening of more than 1,500 drug-resistant strains of Mycobacterium tuberculosis revealed evolutionary patterns characteristic of positive selection for three alanine racemase (Alr) mutations. We investigated these mutations using molecular modeling, in vitro MIC testing, as well as direct measurements of enzymatic activity, which demonstrated that these mutations likely con...
Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium...
Phelan, Jody E.; Coll, Francesc; Bergval, Indra; Anthony, Richard M.; Warren, Rob; Sampson, Samantha L.; Gey van Pittius, Nicolaas C.; Glynn, Judith R.Background: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important vir...
Rapid determination of anti-tuberculosis drug resistance from whole-genome sequ...
Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, MridulPMID: 26019726 WOS:000355073700001; Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was c...
Rapid determination of antituberculosis drug resistance from wholegenome sequen...
Coll, Francesc; McNerney, Ruth; Preston, Mark D.; Guerra-Assunção, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant; Mallard, Kim; Nair, MridulMycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them...
A robust SNP barcode for typing Mycobacterium tuberculosis complex strains
Coll, Francesc; McNerney, Ruth; Guerra-Assunção, José Afonso; Glynn, Judith R.; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Pain, ArnabPMID:25176035 WOS:000342929000002; Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robu...
Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon...
Perdigão, João; Silva, Hugo; Machado, Diana; Macedo, Rita; Maltez, Fernando; Silva, Carla; Jordao, Luisa; Couto, Isabel; Mallard, Kim; Coll, FrancescBACKGROUND: Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. RESULTS: In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The ge...