Faculty Opinions recommendation of AdpA, key regulator for morphological differentiation regulates bacterial chromosome replication.

All bacterial cells must duplicate their genomes prior to dividing into two identical daughter cells. Chromosome replication is triggered when a nucleoprotein complex, termed the orisome, assembles, unwinds the duplex DNA, and recruits the proteins required to establish new replication forks. Obviously, the initiation of chromosome replication is essential to bacterial reproduction, but this process is not inhibited by any of the currently-used antimicrobial agents. Given the urgent need for new antibiotics to combat drug-resistant bacteria, it is logical to evaluate whether or not unexploited bacterial processes, such as orisome assembly, should be more closely examined for sources of novel drug targets. This review will summarize current knowledge about the proteins required for bacterial chromosome initiation, as well as how orisomes assemble and are regulated. Based upon this information, we discuss current efforts and potential strategies and challenges for inhibiting this initiation pharmacologically.

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AdpA, key regulator for morphological differentiation regulates bacterial chromosome replication

Open Biology ◽

10.1098/rsob.120097 ◽

2012 ◽

Vol 2 (7) ◽

pp. 120097 ◽

Cited By ~ 22

Author(s):

Marcin Wolański ◽

Dagmara Jakimowicz ◽

Jolanta Zakrzewska-Czerwińska

Keyword(s):

Streptomyces Coelicolor ◽

Morphological Differentiation ◽

Chromosome Replication ◽

Dependent Manner ◽

Atp Levels ◽

Aerial Hyphae ◽

Preferential Binding ◽

Transcription Regulators ◽

Initiation Stage

AdpA, one of the most pleiotropic transcription regulators in bacteria, controls expression of several dozen genes during Streptomyces differentiation. Here, we report a novel function for the AdpA protein: inhibitor of chromosome replication at the initiation stage. AdpA specifically recognizes the 5′ region of the Streptomyces coelicolor replication origin ( oriC ). Our in vitro results show that binding of AdpA protein decreased access of initiator protein (DnaA) to the oriC region . We also found that mutation of AdpA-binding sequences increased the accessibility of oriC to DnaA, which led to more frequent replication and acceleration of Streptomyces differentiation (at the stage of aerial hyphae formation). Moreover, we also provide evidence that AdpA and DnaA proteins compete for oriC binding in an ATP-dependent manner, with low ATP levels causing preferential binding of AdpA, and high ATP levels causing dissociation of AdpA and association of DnaA. This would be consistent with a role for ATP levels in determining when aerial hyphae emerge.

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