Abstract
Plantaricin 423 is produced by Lactobacillus plantarum 423 using the pla biosynthetic operon located on the 8,188-bp plasmid pPLA4. As with many class IIa bacteriocin operons, the pla operon carries biosynthetic genes (plaA, precursor peptide; plaB, immunity; plaC, accessory; and plaD, ABC transporter) but does not carry local regulatory genes. Little is known about the regulatory mechanisms involved in the expression of the apparently regulationless class IIa bacteriocins, such as plantaricin 423. In this study, phylogenetic analysis of class IIa immunity proteins indicated that at least three distinct clades exist, which were then used to subgroup the class IIa operons. It became evident that the absence of classical quorum-sensing genes on mobile bacteriocin-encoding elements is a predisposition of the subgroup that includes plantaricin 423, pediocin AcH/PA-1, divercin V41, enterocin A, leucocin-A and -B, mesentericin Y105, and sakacin G. Further analysis of the subgroup suggested that the regulation of these class IIa operons is linked to transition metal homeostasis in the host. By using a fluorescent promoter-reporter system in Lactobacillus plantarum 423, transcriptional regulation of plantaricin 423 was shown to be upregulated in response to manganese privation. IMPORTANCE Lactic acid bacteria hold huge industrial application and economic value, especially bacteriocinogenic strains, which further aids in the exclusion of specific foodborne pathogens. Since bacteriocinogenic strains are sought after, it is equally important to understand the mechanism of bacteriocin regulation. This is currently an understudied aspect of class IIa operons. Our research suggests the existence of a previously undescribed mode of class IIa bacteriocin regulation, whereby bacteriocin expression is linked to management of the producer's transition metal homeostasis. This delocalized metalloregulatory model may fundamentally affect the selection of culture conditions for bacteriocin expression and change our understanding of class IIa bacteriocin gene transfer dynamics in a given microbiome.