Suchergebnisse

The authors wish to thank the laboratory, clinical, and nursing staff of HDP, whose high quality of service and cooperation have made this study possible. Financial support was provided by the Fundacao para a Ciencia e a Tecnologia (FCT) Portugal [PTDC/SAU-EPI/122400/2010], part of the EDCTP2 program supported by the European Union. JP was supported by a post doc fellowship from project [PTDC/SAU-EPI/122400/2010] and by fellowship [SFRH/BPD/95406/2013] from FCT. JP is thankful to the European Society of Clinical Microbiology and Infectious Diseases for a Research Grant, and would like to acknowledge the Study Group for Mycobacterial Infections. DM was supported by FCT fellowship [SFRH/BPD/100688/2014] and DM, IC MV are thankful to [GHTM UID/Multi/04413/20139] from FCT. CS was supported by FCT [SFRH/BD/73579/2010]. ; Tuberculosis (TB) poses a serious public health problem in Angola. No surveillance data on drug resistance is available and nothing is known regarding the genetic diversity and population structure of circulating Mycobacterium tuberculosis strains. Here, we have genotyped and evaluated drug susceptibility of 89 Mycobacterium tuberculosis clinical isolates from Luanda. Thirty-three different spoligotype profiles corresponding to 24 different Shared International Types (SIT) and 9 orphan profiles were detected. SIT 20 (LAM1) was the most prevalent (n = 16, 18.2%) followed by SIT 42 (LAM9; n = 15, 17.1%). Overall, the M. tuberculosis population structure in this sample was dominated by LAM (64.8%) and T (33.0%) strains. Twenty-four-loci MIRU-VNTR analysis revealed that a total of 13 isolates were grouped in 5 distinct clusters. Drug susceptibility data showed that 22 (24.7%) of the 89 clinical isolates were resistant to one or more antibacillary drugs of which 4 (4.5%) were multidrug resistant. In conclusion, this study demonstrates a high predominance of LAM strains circulating in the Luanda setting and the presence of recent transmission events. The rate and the emergence dynamics of drug resistant TB found in this sample are significant and highlight the need of further studies specifically focused on MDR-TB transmission. ; publishersversion ; published

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 confer resistance to D-cycloserine. ; Funding Agencies|University of Otago; Health Research Council; Maurice Wilkins Centre; European Union [FP7-278864-2]; German Center for Infection Research (DZIF); Fundacao para a Ciencia e a Tecnologia, Portugal [UID/Multi/04413/2013, SFRH/BPD/100688/2014, SFRH/BPD/95406/2013]; Wellcome Trust [201344/Z/16/Z]; Medical Research Council UK [MR/K000551/1, MR/M01360X/1, MR/N010469/1]; Indian Council of Medical Research, New Delhi; L2 Diagnostics LLC, New Haven; Pacific Biosciences, Inc.; Illumina, Inc.; European Society of Mycobacteriology; Hain Lifescience; UK Department of Health [HICF-T5-342, WT098600]; Wellcome Trust