Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compounds with extremely high Fe3+ affinity. Several lines of evidence suggest that siderophores have a critical role in bacterial iron acquisition inside the human host, where the free iron concentration is well below that required for bacterial growth and virulence. Thus, siderophore biosynthesis is an attractive target in the development of new antibiotics to treat tuberculosis and plague. In particular, such drugs, alone or as part of combination therapies, could provide a valuable new line of defense against intractable multiple-drug-resistant infections. Here, we report the design, synthesis and biological evaluation of a mechanism-based inhibitor of domain salicylation enzymes required for siderophore biosynthesis in M. tuberculosis and Y. pestis. This new antibiotic inhibits siderophore biosynthesis and growth of M. tuberculosis and Y. pestis under iron-limiting conditions.
There is a tendency for non-native English scientists to publish exclusively in English, assuming that this will make their articles more visible and cited. We tested this hypothesis by comparing the effect of language on the number of citations of articles published in six natural sciences journals from five countries that publish papers in either English or other languages. We analyzed the effect of language (English vs non-English), paper length, and year of publication on the number of citations. The articles published in English have a higher number of citations than those published in other languages, when the effect of journal, year of publication, and paper length are statistically controlled. This may result because English articles are accessible to a larger audience, but other factors need to be explored. Universities and scientific institutions should be aware of this situation and improve the teaching of English, especially in the natural sciences.
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