Toxin-
antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable
antitoxin. The
antitoxin can be either a
protein or an
antisense RNA. So far, six different TA gene families, in which the
antitoxins are
proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that supports this inference: expression of the small HicA
protein (58
amino acids [aa]) induced cleavage in three model mRNAs and
tmRNA. Concomitantly, the global rate of translation was severely reduced. Using
tmRNA as a substrate, we show that HicA-induced cleavage does not require the target
RNA to be translated. Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an
antitoxin. As with other
antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces a bacteriostatic rather than a bactericidal condition. Nutrient
starvation induced strong hicAB transcription that depended on
Lon protease. Mining of 218 prokaryotic genomes revealed that hicAB loci are abundant in bacteria and archaea.