Correction: Regulation of the Escherichia coli HipBA Toxin-Antitoxin System by Proteolysis

Abstract

Bacterial populations produce antibiotic-tolerant persister cells. A number of recent studies point to the involvement of toxin/antitoxin (TA) modules in persister formation. hipBA is a type II TA module that codes for the HipB antitoxin and the HipA toxin. HipA is an EF-Tu kinase, which causes protein synthesis inhibition and dormancy upon phosphorylation of its substrate. Antitoxins are labile proteins that are degraded by one of the cytosolic ATP-dependent proteases. We followed the rate of HipB degradation in different protease deficient strains and found that HipB was stabilized in a lonbackground. These findings were confirmed in an in vitro degradation assay, showing that Lon is the main protease responsible for HipB proteolysis. Moreover, we demonstrated that degradation of HipB is dependent on the presence of an unstructured carboxy-terminal stretch of HipB that encompasses the last 16 amino acid residues. Further, substitution of the conserved carboxy-terminal tryptophan of HipB to alanine or even the complete removal of this 16 residue fragment did not alter the affinity of HipB for hipBA operator DNA or for HipA indicating that the major role of this region of HipB is to control HipB degradation and hence HipA-mediated persistence.

A Bacterial Toxin Perturbs Intracellular Amino Acid Balance To Induce Persistence

“…6B ). Because the degradation of the HipB antitoxin by Lon protease in E. coli is necessary for HipA to function as a toxin ( 37 ), we measured Caulobacter HipB2 stabilities in wild-type and lon mutant strains, under conditions of heat shock, acidic stress, and carbon starvation, and found that all three conditions stimulated HipB2 instability, which was not observed in cells lacking Lon ( Fig. 6C ).…”

Recent Advances in Surface Nanoengineering for Biofilm Prevention and Control. Part I: Molecular Basis of Biofilm Recalcitrance. Passive Anti-Biofouling Nanocoatings

“…Since hip B and hip A are on the same hipBA operon, they share the same promoter and are transcribed together. The hipB protein is a transcriptional repressor of the hipBA operon and downregulates its own promoter by cooperatively binding to four operators upstream of hipBA [69,70]. Hence, the expression of the hipBA operon is autoregulated.…”

Unlocking Survival Mechanisms for Metal and Oxidative Stress in the Extremely Acidophilic, Halotolerant Acidihalobacter Genus

“…The contiguous genes associated with IS30 potentially encode the following proteins: (i) A transcriptional regulator of the XRE family with weak similarity to the toxin-antitoxin HipB; (ii) a site specific nuclease type II (Sma-like); (iii) a hypothetical protein with similarity to a site-specific DNA-methyltransferase; (iv) a truncated hypothetical protein with similarity to the toxin-antitoxin HipA that may function with the nearby HipB to form a toxin-antitoxin module potentially involved in the production of non-growing "persister" cells that can lie dormant during stress conditions [96], including metal and oxidative stress and perhaps other stresses. The toxin-antitoxin module has also been implicated in contact inhibition of cell growth, allowing bacteria to recognize kin cells in mixed bacterial populations [97].…”