Abstract
Lantibiotics are antimicrobial peptides that contain non-proteinogenic amino acids lanthionine and 3-methyllanthionine and are produced by Gram-positive bacteria. Here we addressed the pros and cons of lantibiotic production for its producing strains. Two staphylococcal strains, S. gallinarum Tü3928 and S. epidermidis Tü3298 producing gallidermin and epidermin respectively were selected. In each of these parental strains, the structural genes gdmA and epiA were deleted; all the other biosynthetic genes including the immunity genes were left intact. Comparative analysis of the lantibiotic-producing strains with their non-producing mutants revealed that lantibiotic production is a burden for the cells. The production affected growth, caused release of ATP, lipids and increased the excretion of cytoplasmic proteins (ECP). The epidermin and gallidermin immunity genes were insufficient to protect the cells from their own product. Co-cultivation studies showed that the ΔgdmA mutant has an advantage over the parental strain; the latter was outcompeted. On the one hand, the production of staphylococcal lantibiotics is beneficial by suppressing competitors, but on the other hand they impose a burden on the producing-strains when they accumulate in higher amounts. Our observations explain why antibiotic-producing strains occur as a minority on our skin and other ecological niches, but retain corresponding antibiotic resistance.
Highlights
Some Gram-positive bacterial species produce lantibiotics, which are lanthionine containing antimicrobial peptides with a length of usually 19 to 34 amino acids[1,2]
NAI107, a more recently discovered lantibiotic produced by Microbispora ATCC PTA-5024, possesses in total three immunity mechanisms: the MlbYZ ABC-transporter, the accessory membrane protein MlbJ, and the lipoprotein MibQ that is unrelated to LanI and thought to bind the cognate lantibiotic[16]
In order to see whether the production of Gdm and Epi affects growth of the producing-strains, we compared growth of the gdmA and epiA deletion mutants in S. gallinarum Tü3928 and S. epidermidis Tü3298 respectively with its corresponding parental strains
Summary
Some Gram-positive bacterial species produce lantibiotics, which are lanthionine containing antimicrobial peptides with a length of usually 19 to 34 amino acids[1,2]. Lantibiotics such as gallidermin (Gdm), epidermin (Epi), or nisin are ribosomally synthesized in an inactive pre-form, the pro-lantibiotics[3]. Self-defense of S. gallinarum and S. epidermidis is accomplished by LanFEG, of which most likely constitutes an ABC transporter that acts as an efflux pump[13,14] Another immunity mechanism, the lipoprotein NisI binds and sequesters nisin in addition to the action of the NisFEG proteins[15]. TDA caused partial destruction of the proton gradient that leads to a higher energetic demand
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