Siderophores, such as enterobactin (Ent), are small molecules that can be selectively imported into bacteria along with iron by cognate transporters. Siderophore conjugates are thus a promising strategy for delivering functional reagents into bacteria. In this work, we present an easy-to-perform, one-pot chemoenzymatic synthesis of functionalized monoglucosylated enterobactin (MGE). When functionalized MGE is conjugated to a rhodamine fluorophore, which affords RhB-Glc-Ent, it can selectively label Gram-negative bacteria that utilize Ent, including some E. coli strains and P. aeruginosa. V. cholerae, a bacterium that utilizes linearized Ent, can also be weakly targeted. Moreover, the targeting is effective under iron-limiting but not iron-rich conditions. Our results suggest that the RhB-Glc-Ent probe is sensitive not only to the bacterial strain but also to the iron condition in the environment.

Siderophores are small molecules used to specifically transport iron into bacteria via related receptors. By adapting siderophores and hijacking their pathways, we may discover an efficient and selective way to target microbes. Herein, we report the synthesis of a siderophore-fluorophore conjugate VF-FL derived from vibrioferrin (VF). Using flow cytometry and fluorescence microscopy, the probe selectively labeled vibrios, including V. parahaemolyticus, V. cholerae, and V. vulnificus, even in the presence of other species such as S. aureus and E. coli. The labeling is siderophore-related and both iron-limited conditions and the siderophore moiety are required. The competitive relationship between VF-FL and VF in vibrios implies an unreported VF-related transport mechanism in V. cholerae and V. vulnificus. These studies demonstrate that the siderophore scaffold provides a method to selectively target microbes expressing cognate receptors under iron-limited conditions.

A direct and selective method for the functionalization of aerobactin has been described. Selectivity was achieved by masking the functioning carboxylate via iron-chelation, leaving the two remaining carboxylates for direct modification. Both mono- and bis-functionalized aerobactin effectively targeted pathogenic bacteria, showing a facile method with prospective applications.

Siderophores,s uch as enterobactin (Ent), are small molecules that can be selectively imported into bacteria along with iron by cognate transporters.S iderophore conjugates are thus apromising strategy for delivering functional reagents into bacteria. In this work, we present an easy-to-perform, one-pot chemoenzymatic synthesis of functionalizedm onoglucosylated enterobactin (MGE). When functionalizedM GE is conjugated to ar hodamine fluorophore,w hich affords RhB-Glc-Ent, it can selectively label Gram-negative bacteria that utilize Ent, including some E. coli strains and P. aeruginosa. V. cholerae,abacterium that utilizes linearized Ent, can also be weakly targeted. Moreover,the targeting is effective under ironlimiting but not iron-rich conditions.O ur results suggest that the RhB-Glc-Ent probe is sensitive not only to the bacterial strain but also to the iron condition in the environment.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: http://dx.

The cellular mechanisms mediating norepinephrine functions in brain to result in behaviors are unknown. We identified the L-type Ca2+ channel (LTCC) CaV1.2 as a principal target for Gq-coupled a1-adrenergic receptors (ARs). a1AR signaling increased LTCC activity in hippocampal neurons. This regulation required PKC-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with CaV1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of CaV1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by a1AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that CaV1.2 is a central conduit for signaling by norepinephrine. Indeed, a form of hippocampal LTP in young mice requires both the LTCC and a1AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of CaV1.2 activity via a1AR - Pyk2 - Src signaling regulates synaptic strength.