Matthias Wietz

Antibacterial compounds from marine Vibrionaceae isolated on a global expedition.

On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V. neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery.

Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium

During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A marine Photobacterium produced compounds interfering with agr in S. aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium.

Chitin stimulates production of the antibiotic andrimid in a Vibrio coralliilyticus strain

Vibrio coralliilyticus is a putative coral pathogen in tropical oceans, but also possesses antagonistic traits. We previously reported antibacterial activity in Vibrio coralliilyticus strain S2052 based upon the antibiotic andrimid. The purpose of the present study was to determine whether V. coralliilyticus S2052 produces the antibiotic under conditions mimicking natural habitats of vibrios. S2052 synthesized andrimid with both chitin and macroalgal extracts as sole nutrient source. With chitin, the biosynthesis of metabolites other than andrimid was largely abolished, and the yield of the antibiotic per cell was twofold higher. In cultures with Artemia as live chitin model system, S2052 reached up to 10(8)  cells ml(-1) , produced andrimid and showed attachment to the exoskeleton and chitinous exuviae. The metabolic focus on andrimid production with chitin indicates that the antibiotic could serve an ecophysiological function. S2052 was compared with two related V. coralliilyticus strains (LMG20984(T) and LMG10953). Despite overall similar secondary metabolomes, LMG20984(T) and LMG10953 did not produce andrimid, and their optimum biosynthetic temperature was 30 as compared with 25°C for S2052. In addition, S2052 appeared less pathogenic towards Artemia than reported for the type strain. Different physiologies of S2052 and closely related strains indicated that V. coralliilyticus subspecies may be adapted to different niches.

Wide distribution of closely related, antibiotic-producing Arthrobacter strains throughout the Arctic Ocean

ABSTRACT We isolated 16 antibiotic-producing bacterial strains throughout the central Arctic Ocean, including seven Arthrobacter spp. with almost identical 16S rRNA gene sequences. These strains were numerically rare, as revealed using 454 pyrosequencing libraries. Arthrobacter spp. produced arthrobacilins A to C under different culture conditions, but other, unidentified compounds likely contributed to their antibiotic activity.

Nigribactin, a Novel Siderophore from Vibrio nigripulchritudo, Modulates Staphylococcus aureus Virulence Gene Expression

Staphylococcus aureus is a serious human pathogen that employs a number of virulence factors as part of its pathogenesis. The purpose of the present study was to explore marine bacteria as a source of compounds that modulate virulence gene expression in S. aureus. During the global marine Galathea 3 expedition, a strain collection was established comprising bacteria that express antimicrobial activity against Vibrio anguillarum and/or Staphylococcus aureus. Within this collection we searched colony material, culture supernatants, and cell extracts for virulence modulating activity showing that 68 out of 83 marine bacteria (affiliated with the Vibrionaceae and Pseudoalteromonas sp.) influenced expression of S. aureus hla encoding α-hemolysin toxin and/or spa encoding Protein A. The isolate that upon initial screening showed the highest degree of interference (crude ethyl acetate extract) was a Vibrio nigripulchritudo. Extraction, purification and structural elucidation revealed a novel siderophore, designated nigribactin, which induces spa transcription. The effect of nigribactin on spa expression is likely to be independent from its siderophore activity, as another potent siderophore, enterobactin, failed to influence S. aureus virulence gene expression. This study shows that marine microorganisms produce compounds with potential use in therapeutic strategies targeting virulence rather than viability of human pathogens.