Lantibiotic-mediated anti-lactobacillus activity of a vaginal Staphylococcus aureus isolate

Abstract

Staphylococcus aureus strain 26 inhibited the growth of 23 of 26 lactobacilli of endocervical origin, but only two of 17 staphylococci, in deferred antagonism tests. The inhibitory agent, a bacteriocin-like inhibitory substance (BLIS) named staphylococcin Au-26, was obtained from vigorously shaken liquid cultures containing a 0.1% (v/v) supplement of Tween 80 and was purified by chromatographic fractionation on XAD-2, carboxymethyl Sephadex and reversed phase HPLC. The molecular mass of staphylococcin Au-26 was estimated by SDS-PAGE to be approx. 2700. The detection of lanthionine residues in the molecule, the high stability to heating at acidic but not alkaline pH values and inactivation by proteinases indicate that staphylococcin Au-26 is a member of the lantibiotic class of peptide antibiotics--the first reported to be produced by a S. aureus strain. Primary sequence analysis showed that the N-terminus of the molecule is isoleucine, a characteristic also displayed by the lantibiotics nisin, epidermin and gallidermin.

Clinical and Epidemiologic Characteristics Cannot Distinguish Community-Associated Methicillin-Resistant Staphylococcus aureus Infection from Methicillin-Susceptible S. aureus Infection: A Prospective Investigation

“…The presence of seq and sek in the 2 predominant CA-MRSA strains found in this country, USA300 and USA400/MW2, suggests that production of enterotoxins may be sufficient to promote S. aureus colonization and transmission [54]. Production of bacteriocin may further facilitate the spread of USA300 and USA400/MW2 in community settings because of its antimicrobial activity against normal bacteria flora [55]. Finally, the spontaneous excision of the type IV SCCmec element from the chromosome of the methicillin-susceptible USA300 strain (figure 2) suggests that some USA300 isolates may have lost their type IV SCCmec methicillin-resistance determinant and, thus, become MSSA.…”

Production of the Bsa Lantibiotic by Community-Acquired Staphylococcus aureus Strains

“…Previous attempts to elucidate the amino acid sequence of staphylococcin Au-26 were hampered by the presence of a modified residue at position 2 of the peptide, which blocked N-terminal Edman degradation assays. It was established, however, that the first residue in this peptide (estimated to have a mass of 2,700 Da) is an isoleucine and that the peptide contains two or three lanthionine residues and thus is likely to be a lantibiotic (63). Given that isoleucine is also the first residue of the S. To assess this possibility, we designed two degenerate primers, one (StaphLanF) designed on the basis of nucleotides conserved within epidermin-encoding genes and a second (StaphLanBR) designed to amplify a region conserved across genes encoding lantibiotic-modifying proteins, i.e., lanB homologues, in a manner analogous to that described previously (31,73).…”

“…Antibiotics were used, where indicated, at the following concentrations: chloramphenicol, 10 g ml Ϫ1 for E. coli and 10 g ml Ϫ1 for S. aureus, and erythromycin, 250 g ml Ϫ1 for E. coli and 5 g ml Ϫ1 for S. aureus. X-Gal (5-bromo-4-chloro-3-indoyl-␤-D-galactopyranoside) was used at a concentration of 40 g ml supplemented with 0.1% Tween 80, by using cation exchange on XAD-2 resin followed by reverse-phase high-performance liquid chromatography (HPLC) as described previously (63). Fractions separated during chromatography were assayed for biological activity by being spotted in 20-l aliquots onto a freshly seeded lawn of M. luteus cells on Columbia blood agar.…”

“…Given that strain 26 was originally recovered from an endocervical environment, one could hypothesize that Au-26 plays a role in staphylococcal toxic shock syndrome. However, strain 26 was not associated with this disease and does not express toxic shock syndrome toxin 1 (63). In addition, an in silico survey of the prevalence of the tst gene reveals that only strain ET3-1 carries both the lantibiotic-encoding genes and tst.…”

“…Indeed, to date, there has been only one confirmed example of a lantibiotic, i.e., staphylococcin C55 (46), produced by S. aureus and no definitive evidence that CA-(or HA)-MRSA strains produce such compounds. There is, however, some evidence to suggest that staphylococcin Au-26, which is produced by a vaginal isolate of S. aureus and has an inhibitory spectrum encompassing lactobacilli isolated from the endocervix and representative strains of Staphylococcus hominis, Staphylococcus warneri, Streptococcus pyogenes, Streptococcus salivarius, Streptococcus mutans, Lactococcus spp., and oral Neisseria spp., may also be a lantibiotic (63). Here, 17 years after its initial characterization, we have carried out a closer inspection of staphylococcin Au-26 and the associated producer and have established that the staphylococcin Au-26 and Bsa genetic loci are almost identical.…”