MT participated in conceiving and designing the study. BM designed the microarray. SH participated in the microarray experiments and participated in drafting the Methods section. MH carried out the patient interviews and the epidemiological analysis and participated in drafting the Methods BVD-523 mouse section. HC participated in conceiving and designing
the study. EMN participated in conceiving and designing the study. All authors read and approved the final manuscript.”
“Background Due to their genetic and phenotypic diversity, epidemiological and pathological studies of non-tuberculous mycobacteria are complex. These bacteria are difficult to eradicate because of their natural resistance to the antibiotics frequently used against tuberculosis. Because of their saprophytic and ubiquitous nature, the diagnosis of non-tuberculous mycobacterial disease depends on criteria provided by the American Thoracic
Society (ATS) [1]. Mycobacterium intracellulare belongs to the Mycobacterium avium complex, and has an important role in pathology. In humans, Pritelivir M. intracellulare may be the cause of severe lung, lymphatic node, skin and bone/joint infections, as well as bacteriemia [2]. The presence of an immunodepressing context, like that caused by HIV/AIDS, constitutes a risk factor for the M. avium infection, but not for the M. intracellulare infection. M. intracellulare is more frequently isolated at infection stages, as defined by the ATS, than is M. avium [3, 4]. Most available methods to identify and differentiate strains of M. intracellulare are difficult and have limited discriminatory power. The PCR-RFLP method has been used for the typing of M. avium [5]. The repeated sequences of VNTR (Variable-Number of Tandem-Repeats), and in particular MIRU (Mycobacterial Interspersed Repetitive Units) have been used for the genotyping of several species of non-tuberculous mycobacteria. The full genomes of M. avium and M. paratuberculosis have been sequenced
allowing the description of MIRU-VNTR in these species [6–9]. MIRU-VNTR markers applied to the genetic typing of M. intracellulare have been described very recently (-)-p-Bromotetramisole Oxalate [10]. The full genome of M. intracellulare has not been published yet, but the sequences of 353 contigs from M. intracellulare ATCC 13950 have been publicly available since 2008. The goal of our work was to identify MIRU-VNTR markers from the genome sequence of M. intracellulare ATCC 13950 and to study their variation in a collection of 61 M. intracellulare isolates collected at infection or colonizing stages, as defined by the ATS, and from pulmonary or extra-pulmonary sites. Methods Strain collection Different MIRU-VNTR were studied in a group including 61 M. intracellulare isolates collected under colonization (10 isolates) or infection stages (51 isolates) in humans, and the reference strain M. intracellulare ATCC 13950, named strain 1 in our study.