An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death.

"Addiction modules" consist of two genes. In most of them the product of one is long lived and toxic while the product of the second is short lived and antagonizes the toxic effect; so far, they have been described mainly in a number of prokaryotic extrachromosomal elements responsible for the postsegregational killing effect. Here we show that the chromosomal genes mazE and mazF, located in the Escherichia coli rel operon, have all of the properties required for an addiction module. Furthermore, the expression of mazEF is regulated by the cellular level of guanosine [corrected] 3',5'-bispyrophosphate, the product of the RelA protein under amino acid starvation. These properties suggest that the mazEF system may be responsible for programmed cell death in E. coli and thus may have a role in the physiology of starvation.

Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine protease of Escherichia coli.

Plasmid-encoded addiction genes augment the apparent stability of various low copy number bacterial plasmids by selectively killing plasmid-free (cured) segregants or their progeny. The addiction module of plasmid prophage P1 consists of a pair of genes called phd and doc. Phd serves to prevent host death when the prophage is retained and, should retention mechanisms fail, Doc causes death on curing. Doc acts as a cell toxin to which Phd is an antidote. In this study we show that host mutants with defects in either subunit of the ClpXP protease survive the loss of a plasmid that contains a P1 addiction module. The small antidote protein Phd is fully stable in these two mutant hosts, whereas it is labile in a wild-type host. We conclude that the role of ClpXP in the addiction mechanism of P1 is to degrade the Phd protein. This conclusion situates P1 among plasmids that elicit severe withdrawal symptoms and are able to do so because they encode both a cell toxin and an actively degraded macromolecule that blocks the synthesis or function of the toxin.

Principles of drug addiction treatment : a research-based guide.

"Reprinted July 2000"--P. [4] of cover.

Fortescutus illustratus, or a commentary on that nervous treatise De laudibus legum Angliæ, written by Sir John Fortescue ... VVhich treatise ... hee purposely wrote to consolidate his princely minde in love and approbation of the good lawes of England and of the laudable customs of this his native country. The heroique design of whole excellent judgement and loyal addiction to his Prince, is humbly endeavoured to be revived, admired, and advanced.

Mode of access: Internet.

Self-run, self-supported houses for more effective recovery from alcohol and drug addiction /

Mode of access: Internet.

Annotated bibliography of papers from the Addiction Research Center, 1935-75

Includes index

Drug addiction and the U.S. Public Health Service : proceedings of a symposium commemorating the 40th anniversary of the Addiction Research Center at Lexington, Ky. /

Mode of access: Internet.

Drug addiction act and related statutes.

Mode of access: Internet.