Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

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Crustins are antibacterial proteins of ca 7-14 kDa with a characteristic four disulphide corecontaining whey acidic protein (WAP) domain, expressed by the circulating haemocytes of crustaceans.Over 50 crustin sequences have been now reported from a variety of decapods, including crabs, lobsters, shrimp and crayfish. Three main types seem to occur but all possess a signal sequence at the amino terminus and a WAP domain at the carboxyl end. Differences between types lie in the structure of the central region. Those crustins purified as the native protein or expressed recombinantly all kill Gram-positive bacteria, and gene studies have shown that they are constitutively expressed, often at high levels, but show no consistent patterns of change in expression following injection of bacteria. This variable response to infection is enigmatic but indicates that these proteins could perform additional functions, perhaps as immune regulators in recovery from wounding, trauma or physiological stress.Prof Kenneth Soderhall Co-Editor in Chief Developmental and Comparative Immunology Dear Kenneth I attach the revised manuscript for the invited review, Crustins: enigmatic WAP domaincontaining antibacterial proteins from crustaceans, for which all the referees comments have been addressed. Below is a summary of changes made.1. Two of the reviewers have issues with the SS tree (formerly Fig 2), with reviewer 2 making the point that the functional WAP domain will more usefully indicate relationships rather than the SS. We do not concur with the comment that the signal sequence (SS) tree is unnecessary but do accept that its placement in the article could be better and that it could be more fully discussed. Importantly, the SS radiation tree did not drive the 3-type classification, rather it was led by the overall domain organisation of the various types that we judged, from our starting definition, to be within the crustin 'family'. The region of variation is mainly in the 'central' region of the molecule, ie between the SS and WAP domain. We constructed the SS and WAP domain trees to test if the suggested classification was supported, independently by phylogenies within these regions. We believe that they do and the inclusion of both trees, rather than just a tree for the WAP domain, makes the case for the classification of crustins into Types I, II or III, even stronger. We have therefore retained the SS radiation tree but discuss it more fully in the section on 'Relationships' (new pages 11 & 12) rather than its former position. We prefer not to add species identifiers to the as these will make it very 'busy' and untidy. We feel that Accession numbers are more appropriate than species names. Please note we have slightly modified the annotations by leaving ambiguous sequences out of the clusters marked by dotted or dashed lines.2. Referee 1 correctly points out that the argument (beginning in the last paragraph on pg 6 and continued on pg 7in the original m/s) that the signal sequence is probably not involved in crust...