The biology of lantibiotics from the lacticin 481 group is coming of age

Abstract

Lantibiotics are antimicrobial peptides from the bacteriocin family, secreted by Gram-positive bacteria. These peptides differ from other bacteriocins by the presence of (methyl)lanthionine residues, which result from enzymatic modification of precursor peptides encoded by structural genes. Several groups of lantibiotics have been distinguished, the largest of which is the lacticin 481 group. This group consists of at least 16 members, including lacticin 481, streptococcin A-FF22, mutacin II, nukacin ISK-1, and salivaricins. We present the first review devoted to this lantibiotic group, knowledge of which has increased significantly within the last few years. After updating the group composition and defining the common properties of these lantibiotics, we highlight the most recent developments. The latter concern: transcriptional regulation of the lantibiotic genes; understanding the biosynthetic machinery, in particular the ability to perform in vitro prepeptide maturation; characterization of a novel type of immunity protein; and broad application possibilities. This group differs in many aspects from the best known lantibiotic group (nisin group), but shares properties with less-studied groups such as the mersacidin, cytolysin and lactocin S groups.

Core Principles of Bacterial Autoinducer Systems

“…to "What information does the cell get, and how can it benefit?" This is in accordance with the hypothesis that many AIs or their evolutionary precursors may have originally been released for other purposes, e.g., as siderophores, as antibiotics, or simply as waste products (22,(49)(50)(51). Only in a secondary evolutionary process would cells have realized the additional value of information contained in the local concentration of these substances: it allows prediction of the efficiency (i.e., cost-effectivity) of the release of other effectors (52).…”

“…Additionally, existing AI systems that evolved in other bacterial species may have been acquired by horizontal gene transfer and brought the expression of these effectors under their transcriptional control (53). Interestingly, some AIs, including certain AHLs and bacteriocins, still also function as antibiotics or siderophores (49,50).…”

Evolution of lanthipeptide synthetases

“…Type IIA compounds are structurally similar to the prototypical peptide lacticin 481, which possesses a linear N terminus and a globular C-terminal scaffold (SI Appendix, Fig. S8) (6,32). The close correlation of the enzyme phylogeny and the structure of the final products demonstrate that these products evolved from the same ancestors, in contrast to the apparent convergent evolution of several members of the nisinlike peptides discussed above.…”

Fundamental functionality: recent developments in understanding the structure–activity relationships of lantibiotic peptides

“…23 Mutagenesis has been used to produce weakly active analogs containing the changes S4T, H8P, Q20T and truncation at S27. 24,25 The importance of the ring structures in lacticin 481 has also been studied. 23 It appears that each ring can exist as either lan or melan and the peptide remains active.…”