Effects of dual deletion of glnR and mtrA on expression of nitrogen metabolism genes in Streptomyces venezuelae

GlnR activates nitrogen metabolism genes under nitrogen-limited conditions whereas MtrA represses these genes under nutrient-rich conditions in Streptomyces. In this study, we compared the transcription patterns of nitrogen metabolism genes in a double deletion mutant (ΔmtrA-glnR) lacking both mtrA and glnR and in mutants lacking either mtrA (ΔmtrA) or glnR (ΔglnR). The nitrogen metabolism genes were expressed similarly in ΔmtrA-glnR and ΔglnR under both nitrogen-limited and nutrient-rich conditions, with patterns distinctly different from that of ΔmtrA, suggesting a decisive role for GlnR in the control of nitrogen metabolism genes and further suggesting that regulation of these genes by MtrA is GlnR-dependent. MtrA and GlnR utilize the same binding sites upstream of nitrogen metabolism genes, and we showed stronger in vivo binding of MtrA to these sites under nutrient-rich conditions and of GlnR under nitrogen-limited conditions, consistent with the higher levels of MtrA or GlnR under those respective conditions. In addition, we showed that both mtrA and glnR are auto-regulatory. Our study provides new insights into the regulation of nitrogen metabolism genes in Streptomyces.

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De novo identification of in vivo binding sites from ChIP-chip data

BMC Bioinformatics ◽

10.1186/1471-2105-9-s7-p24 ◽

2008 ◽

Vol 9 (S7) ◽

Author(s):

Victor Jin ◽

Alina Rabinovich ◽

Henny O'Geen ◽

Sushma Iyengar ◽

Peggy Farnham

Keyword(s):

Binding Sites ◽

De Novo ◽

Chip Data ◽

In Vivo Binding ◽

Chip Chip

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E2F in vivo binding specificity: Comparison of consensus versus nonconsensus binding sites

Genome Research ◽

10.1101/gr.080622.108 ◽

2008 ◽

Vol 18 (11) ◽

pp. 1763-1777 ◽

Cited By ~ 96

Author(s):

A. Rabinovich ◽

V. X. Jin ◽

R. Rabinovich ◽

X. Xu ◽

P. J. Farnham

Keyword(s):

Binding Sites ◽

Binding Specificity ◽

In Vivo Binding

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Na+/H+Antiport Is Essential for Yersinia pestis Virulence

Infection and Immunity ◽

10.1128/iai.00071-13 ◽

2013 ◽

Vol 81 (9) ◽

pp. 3163-3172 ◽

Cited By ~ 28

Author(s):

Yusuke Minato ◽

Amit Ghosh ◽

Wyatt J. Faulkner ◽

Erin J. Lind ◽

Sara Schesser Bartra ◽

...

Keyword(s):

Yersinia Pestis ◽

Drug Target ◽

Deletion Mutant ◽

Ex Vivo ◽

Ion Homeostasis ◽

Content Type ◽

Double Deletion ◽

Derivative Strain

ABSTRACTNa+/H+antiporters are ubiquitous membrane proteins that play a central role in the ion homeostasis of cells. In this study, we examined the possible role of Na+/H+antiport inYersinia pestisvirulence and found thatY. pestisstrains lacking the major Na+/H+antiporters, NhaA and NhaB, are completely attenuated in anin vivomodel of plague. TheY. pestisderivative strain lacking thenhaAandnhaBgenes showed markedly decreased survival in blood and blood serumex vivo. Complementation of eithernhaAornhaBintransrestored the survival of theY. pestis nhaA nhaBdouble deletion mutant in blood. ThenhaA nhaBdouble deletion mutant also showed inhibited growth in an artificial serum medium, Opti-MEM, and a rich LB-based medium with Na+levels and pH values similar to those for blood. Taken together, these data strongly suggest that intact Na+/H+antiport is indispensable for the survival ofY. pestisin the bloodstreams of infected animals and thus might be regarded as a promising noncanonical drug target for infections caused byY. pestisand possibly for those caused by other blood-borne bacterial pathogens.

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