INVESTIGADORES
FERRERAS Julian Alberto
artículos
Título:
Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis.
Autor/es:
FERRERAS JA, RYU JS, DI LELLO F, TAN DS, QUADRI LE
Revista:
Nature Chemical Biolgoy
Referencias:
Año: 2005 vol. 1 p. 29 - 32
ISSN:
1552-4450
Resumen:
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.