The cytotoxic enterotoxin of Aeromonas hydrophila is aerolysin.

The channel-forming toxin aerolysin was identified 25 years ago by Bernheimer and Avigad (1), who gave the protein its name. Aerolysin was purified by Buckley et al. (2), and its structural gene, named aerA, was cloned and sequenced almost simultaneously by two groups (6, 7). Since then more than 50 articles describing the expression, secretion, and properties of aerolysin have appeared, and aerolysin has become one of the best-characterized bacterial channel-forming toxins. Virtually all of the available evidence indicates that aerolysin kills cells by forming discrete channels in their plasma membranes (for a recent review, see reference 8). Although it is certainly cytotoxic, it has not been shown to directly alter cyclic nucleotide levels and therefore does not satisfy the definition of an enterotoxin. Two articles in Infection and Immunity from the group of Chopra have described the purification and mechanism of action (5), and the role in Aeromonas-mediated infection (9), of a cytotoxic enterotoxin from A. hydrophila. The authors state that their protein (referred to as “Act”) is “an aerolysin-related toxin.” In fact, this protein is aerolysin. Its amino acid sequence is essentially the same as the six other aerolysin sequences (from different Aeromonas strains or species) retrieved by a BLAST search (five of these are referred to as aerolysin and the other as a hemolysin). For example, 416 (97%) of the 427 amino acids in the active, biologically relevant form of the protein described by Chopra’s group (accession no. 2126218) are the same as those in the first aerolysin sequence which was obtained (accession no. 113485), and 6 of the 11 differences are conservative. All of the properties of the protein described by the Chopra group have previously been described for aerolysin, with one minor apparent exception. In one article (4) it is pointed out that the results of mutagenesis of the cytotoxic enterotoxin do not completely correspond to results reported for aerolysin. However, the authors were not working with purified proteins in this study, nor was there evidence that they had confirmed each of the changes they attempted. The fact that Chopra et al. do not refer to their protein as aerolysin is not productive. Medline searches using aerolysin as a key word do not locate all of their relevant articles, because aerolysin does not appear in the titles, abstracts, or key words. It is difficult to compare their findings with those of others and to determine if data are being duplicated. This is most recently illustrated in their last Infection and Immunity article, in which they describe the testing in a lethal mouse assay of mutants which do not produce cytotoxic enterotoxin (9), comparable to work done 10 years ago with the same results (3). We believe that the authors should use the word aerolysin to describe their protein, as all other groups have done, or they should provide convincing evidence that they are working with a different toxin.