The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria.The Mycobacterium genus comprises more than 70 species, including the major human pathogens responsible for tuberculosis (Mycobacterium tuberculosis, Mycobacterium africanum, and Mycobacterium bovis) and leprosy (Mycobacterium leprae). This genus also includes soil saprophytes and water microorganisms, some of which (e.g., those belonging to the Mycobacterium avium complex) can cause opportunistic infections, especially in immunocompromised patients. Mycobacteria are intrinsically resistant to most commonly used antibiotics and chemotherapeutic agents. Due to its specific structure and composition, the mycobacterial cell wall is an effective permeability barrier, considered to be a major factor in promoting this natural resistance (25). Only a few drugs are active against mycobacteria, and the emergence of multidrug-resistant M. tuberculosis strains is becoming a major problem worldwide (16).Macrolides inhibit protein synthesis in a wide range of bacteria by binding to the large ribosomal subunit (18,23). Like other protein synthesis inhibitors that affect the large subunit, they can also prevent the formation of the 50S particle in growing cells (8). Natural macrolides, such as erythromycin, are not effective against mycobacteria, but semisynthetic derivatives, such as clarithromycin and azithromycin, have stronger antimycobacterial activities a...

Sixteen sequence-tagged sites (STSs) were combined in five amplification reactions, to screen for deletions of DNA fragments located within the AZFa, AZFb, and AZFc regions of the Y chromosome. This multiplex strategy is fast and reliable, and most of the azoospermia-associated deletions reported so far are detected with this simplified method. Internal control STSs are included that allow discrimination between deletion and failure of amplification.

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