High frequency and diversity of antimicrobial activities produced by nasal Staphylococcus strains against bacterial competitors

The human nasal microbiota is highly variable and dynamic often enclosing major pathogens such as Staphylococcus aureus. The potential roles of bacteriocins or other mechanisms allowing certain bacterial clones to prevail in this nutrient-poor habitat have hardly been studied. Of 89 nasal Staphylococcus isolates, unexpectedly, the vast majority (84%) was found to produce antimicrobial substances in particular under habitat-specific stress conditions, such as iron limitation or exposure to hydrogen peroxide. Activity spectra were generally narrow but highly variable with activities against certain nasal members of the Actinobacteria, Proteobacteria, Firmicutes, or several groups of bacteria. Staphylococcus species and many other Firmicutes were insusceptible to most of the compounds. A representative bacteriocin was identified as a nukacin-related peptide whose inactivation reduced the capacity of the producer Staphylococcus epidermidis IVK45 to limit growth of other nasal bacteria. Of note, the bacteriocin genes were found on mobile genetic elements exhibiting signs of extensive horizontal gene transfer and rearrangements. Thus, continuously evolving bacteriocins appear to govern bacterial competition in the human nose and specific bacteriocins may become important agents for eradication of notorious opportunistic pathogens from human microbiota

Cacti, Braids and Complex Polynomials

The study of the topological classification of complex polynomials began in the XIX-th century by Luroth (1871), Clebsch (1873) and Hurwitz (1891). In the works of Zdravkovska [23] and Khovanskii and Zdravkovska [17] the problem is reduced to a purely combinatorial one, that of the study of a certain action of the braid groups on a class of tree-like figures that we, following [14], call "cacti". Using explicit computation of the braid group orbits, enumerative results of [14], and also establishing some combinatorial invariants of the action, we provide the topological classification of polynomials of degree up to 9 (previous results were known up to degree 6). R'esum'e L"etude de la classification topologique des polynomes complexes a commenc'e au XIX-`eme siecle par Luroth (1871), Clebsch (1873) et Hurwitz (1891). Dans les travaux de Zdravkovska [23] et Khovanskii et Zdravkovska [17] le probl`eme est r'eduit `a une 'etude purement combinatoire d'une certaine action du groupe des t..

Antibacterial activity of IVK45 wild type compared to nukacin deletion mutant and complemented mutant.

<p>A: IVK 45 wild type (1); nukacin-deficient mutant Δ<i>nukA</i> (2); and complemented mutant (3) on <i>M</i>. <i>luteus</i> lawns. B: <i>M</i>. <i>luteus</i> cultures supplemented with 20% and 40% supernatant (SN) of IVK 45 wild type and nukacin-deficient mutant; C: <i>M</i>. <i>catarrhalis</i> cultures in spent medium or supplemented with 4-fold concentrated activity of IVK 45 wild type and nukacin-deficient mutant; D: <i>C</i>. <i>accolens</i> cultures in spent medium or supplemented with 50% supernatant of IVK 45 wild type and nukacin-deficient mutant; E: Nukacin insensitive <i>S</i>. <i>aureus</i> Newman cultures supplemented with 40% and 80% supernatant of IVK 45 wild type and nukacin-deficient mutant as negative control.</p

Nukacin IVK 45 operon, predicted peptide structure and composition of plasmid pIVK45.

<p>A: comparison of the operon structures from <i>S</i>. <i>warneri</i> ISK-1 (top) and <i>S</i>. <i>epidermidis</i> IVK45 (bottom), Tn: insertion site of the transposon. B: Predicted structure of nukacin IVK45. Amino acid positions of nukacin IVK45, which are different in corresponding peptides from <i>S</i>. <i>warneri</i> ISK-1 and <i>S</i>. <i>hominis</i> KQU-131 are shown in grey. The additional different amino acid in <i>S</i>. <i>hominis</i> KQU-131 is shown in a grey pattern; A-S-A, lanthionine (thioether bridge between cysteine and serine); Abu-S-A, 3-methyllanthionine (thioether bridge between cysteine and threonine); Abu, aminobutyrate (threonine within the methyllanthionine ring); Dhb, dehydrobutyrine (dehydrated threonine). C: Intact genes or fragments for transposases, recombinases, IS- and IS-like elements indicate multiple recombination events in the genesis of pIVK45. Outer ring of plasmid: identified genes are indicated by arrows. Inner ring: The color of the various segments indicates their most likely species origin (analyzed by BLAST). Red: <i>S</i>. <i>warneri</i>, blue: <i>S</i>. <i>aureus</i>, light green: <i>S</i>. <i>epidermidis</i>, dark green: <i>S</i>. <i>aureus</i> and <i>S</i>. <i>epidermidis</i>, yellow: <i>S</i>. <i>lugdunensis</i>, lilac: many different <i>Staphylococcus</i> species, light blue: IS-like element. White segments show unique DNA fragments with no homologies in available databases.</p

Co-cultivation of <i>M</i>. <i>catarrhalis</i> and <i>S</i>. <i>epidermidis</i> IVK45 strains.

<p><i>S</i>. <i>epidermidis</i> IVK45 wild type and mutant IVK45 Δ<i>nukA</i> (black) were inoculated at ratios of 3:1 with <i>M</i>. <i>catarrhalis</i> (grey) on solid agar. <i>M</i>. <i>catarrhalis</i> is overgrown by the nukacin-producing IVK45 wild type after 48 hours. In contrast, the numbers of the nukacin-deficient mutant IVK45 Δ<i>nukA</i> and <i>M</i>. <i>catarrhalis</i> shift towards a ratio of 1:1 after 48 hours. Significant differences between the IVK45 wild type and mutant Δ<i>nukA</i> ratios after 48 hours were analyzed by two tailed paired t-test (** <i>P</i> < 0.005).</p

Primers used in this study.

<p>Primers used in this study.</p

Frequency of antimicrobial activitiy in nasal <i>Staphylococcus</i> isolates.

<p>Frequency of antimicrobial activitiy in nasal <i>Staphylococcus</i> isolates.</p

Frequency and activity spectra of antimicrobial substances produced by nasal <i>Staphylococcus</i> isolates.

<p>Pattern and intensity of test strain inhibition by nasal <i>Staphylococcus</i> isolates is shown as a heat map. They are ordered hierarchically by activity patterns according to the number and identity of inhibited strains (indicated by numbers in the last column) against <i>Actinobacteria</i> (A-E); <i>Proteobacteria</i> (F-G); <i>Firmicutes</i> (H-J). (i) indicates inducible bacteriocin production, which was only visible under iron-limitation stress. MLST types are given for 19 <i>S</i>. <i>epidermidis</i> strains and <i>spa</i>-types are indicated for all <i>S</i>. <i>aureus</i> isolates. (n.t.; non-typeable).</p

Bacteriocin induction by iron limitation or H₂O₂.

<p>Intensity of inhibitory activities of IVK strains 1–96 against <i>M</i>. <i>luteus</i> or <i>S</i>. <i>aureus</i> without stressors (normal) or in the presence of 2,2’-bipyridine (iron limitation) or H₂O₂ (H₂O₂ stress).</p