Arabidopsis growth and reproduction are stimulated by the endophytic fungus Piriformospora indica. The fungus produces low amounts of auxins, but the auxin levels and the expression of auxin-regulated genes are not altered in colonized roots. Also, mutants with reduced auxin levels (ilr1-1, nit1-3, tfl2, cyp79 b2b3) respond to P. indica. However, the fungus rescues the dwarf phenotype of the auxin overproducer sur1-1 by converting free auxin into conjugates, which also results in the downregulation of the auxin-induced IAA6 and the upregulation of the P. indica-induced LRR1 gene. The fungus produces relatively high levels of cytokinins, and the cytokinin levels are higher in colonized roots compared with the uncolonized controls. trans-Zeatin cytokinin biosynthesis and the CRE1/AHK2 receptor combination are crucial for P. indica-mediated growth stimulation, while mutants lacking cis-zeatin, impaired in other cytokinin receptor combinations, or containing reduced cytokinin levels respond to the fungus. Since root colonization is not affected in the cytokinin mutants, we propose that cytokinins are required for P. indica-induced growth promotion. Finally, a comparative analysis of the phytohormone mutants allows the conclusion that the response to P. indica is independent of the architecture and size of the roots.
Since numbers of drug-resistant Mycobacterium tuberculosis strains are on the rise, the simple classification into "susceptible" and "resistant" strains based on susceptibility testing at "critical concentrations" has to be reconsidered. While future studies have to address the correlation of phenotypic resistance levels and treatment outcomes, a prerequisite for corresponding investigations is the ability to exactly determine levels of quantitative drug resistance in clinical M. tuberculosis isolates. Here we have established the conditions for quantitative drug susceptibility testing for first-and second-line agents using MGIT 960 instrumentation and EpiCenter software equipped with the TB eXiST module. In-depth comparative analysis of a range of wellcharacterized susceptible and resistant clinical isolates has allowed us to propose conditions for testing and to develop criteria for interpretation.Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Developing countries are the most vulnerable, with more than 95% of the cases (32, 33). The present trend is characterized by an alarming emergence of drug resistance (7,8,30). Much attention has focused on the burden of multidrug-resistant (MDR) TB, i.e., resistance to the firstline drugs isoniazid and rifampin (rifampicin) (32,33), and the emergence of extensively drug resistant TB (6, 26). The rise of drug-resistant TB and the increased susceptibility of the human population to TB due to coinfection with human immunodeficiency virus are driving the worldwide TB pandemic and will worsen the situation in the years ahead, with devastating effects in poor countries, whose economies suffer most from this development (19,20).In the diagnostic laboratory, testing of mycobacteria for drug susceptibility is substantially different from the general testing procedures used in bacteriology. Rather than determining MICs, a single drug concentration, termed the critical concentration, is usually used to categorize a clinical isolate as susceptible or resistant. This "critical concentration" is more an epidemiological parameter (to distinguish "wild-type" strains from "non-wild-type" strains that are able to grow in the presence of higher drug concentrations [5]) than a clinical cutoff value established to guide treatment decisions (14). With growing knowledge about the mechanisms that underlie drug resistance, it has become evident that drug resistance is multifaceted and that different mutations may lead to different levels of resistance. The acquisition of a resistance mutation leading to a decrease in drug susceptibility should not inevitably exclude an anti-TB drug from a treatment regimen, since low-level resistance does not necessarily imply clinical resistance (3). However, until now, different levels of phenotypic resistance have only rarely been taken into account in the procedures used for in vitro drug susceptibility testing (DST) of mycobacteria (4)."Critical concentration"-based DST of primary and secondary drugs has been established for the...
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