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Andersen, A. J. C.

Publications and source records attributed to Andersen, A. J. C..

4 recordsLinked to original sources

Secondary metabolites shape Streptomyces-Streptomyces interaction: Mass Spectrometry Imaging reveals lydicamycins broadly induce sporulation

Streptomyces are major players in soil microbiomes, however, interactions involving Streptomyces and other actinobacteria are rarely described. The complex developmental cycle of actinobacteria necessitates a multi-omics approach to unravel the web of information. This study resulted from the observation of induced morphogenesis between two environmental isolates from the same site, Kitasatospora sp. P9-2B1 and Streptomyces sp. P9-2B2. When co-cultivated on potato dextrose agar (PDA), P9-2B2 induced a wave-like sporulation in strain P9-2B1. Using mass spectrometry imaging, we revealed that a suite of lydicamycins were present in this induced sporulation zone. Lydicamycin deficient mutants were generated using CRISPR Base-Editing and the inducible sporulation ceased, confirming their role in triggering morphological differentiation. In agar diffusion assays, pure lydicamycin was inhibitory when added concurrently with bacterial inoculation and induced sporulation with delayed addition. Subsequent testing of additional environmental isolates resulted in the same inducible sporulation wave phenomenon, including Streptomyces coelicolor M145 and M1146. Using transcriptomics, we observed the differential expression of genes related to early aerial mycelium development four days into cocultivation and the transitional genes responsible for development of spores on day 9. Along with these differentially expressed genes, we also observed numerous overall stress responses, specifically cell envelope stress responses. These findings uncovered actinobacteria interactions mediated by lydicamycins, pointing to a potential role of certain groups of bioactive metabolites in nature. ImportanceShifting away from an antibiotic discovery mindset, uncovering the chemical ecology of secondary metabolites is key to maximizing their biotechnological application. The reduced complexity of dual cultures allows for in depth analysis and investigation of these interactions via multi-omics provides orthogonal data leading to more robust conclusions. This study provides insight into the role of lydicamycins in dual cultures with other actinobacteria and provides an integral roadmap for future chemical ecology work between microorganisms, especially through the use of mass spectrometry imaging.

ecology↗

Insights into the nature of the microalgal toxins from the Chrysochromulina leadbeateri blooms in Northern Norwegian fjords

In May-June 2019, the microalga Chrysochromulina leadbeateri caused a massive fish-killing event in several fjords in Northern Norway, resulting in the largest direct impact ever on aquaculture in northern Europe due to toxic algae. Motivated by the fact that no algal toxins have previously been described from C. leadbeateri, we set out to investigate the chemical nature and toxicity of secondary metabolites in extracts of two strains (UIO 393, UIO 394) isolated from the 2019 bloom, as well as one older strain (UIO 035) isolated during a bloom in Northern Norway in 1991. Initial LC-DAD-MS/MS-based molecular networking analysis of the crude MeOH extracts of the cultivated strains showed that their profiles of small organic molecules, including a large number of known lipids, were very similar, suggesting that the same class of toxin(s) were likely the causative agents of the two harmful algal bloom (HAB) events. Next, bioassay-guided fractionation using the RTgill-W1 cell line and metabolomics analysis pointed to a major compound affording [M+H]+ ions at m/z 1399.8333 as a possible toxin, corresponding to a compound with the formula C67H127ClO27. Moreover, our study unveiled a series of minor analogues exhibiting distinct patterns of chlorination and sulfation, together defining a new family of compounds, which we propose to name leadbeaterins. Remarkably, these suspected toxins were detected in situ in samples collected during the 2019 bloom close to Tromso, thereby substantiating their likely role in fish kills. The elemental compositions of the putative C. leadbeateri ichthyotoxins strongly indicate them to be long linear polyhydroxylated polyketides, structurally similar to sterolysins, reported from a number of dinoflagellates.

ecology↗

Resistance towards and biotransformation of Pseudomonas-produced secondary metabolites during community invasion

The role of antagonistic secondary metabolites produced by Pseudomonas protegens in suppression of soil-borne phytopathogens has been clearly documented. However, their contribution to the ability of P. protegens to establish in soil and rhizosphere microbiomes remains ambiguous. Here, we use a four-species synthetic community to determine how antibiotic production contributes to P. protegens community invasion and identify community traits that alter the abundance of key P. protegens antimicrobial metabolites (DAPG, pyoluteorin and orfamide A). Surprisingly, mutants deficient in antimicrobial production caused similar perturbations in community composition compared to invasion by wildtype P. protegens. Intriguingly, while pyoluteorin and orfamide A are secreted at levels toxic to individual bacterial strains, community-level resistance circumvents toxicity. Here, we identify the underlying mechanism by which the cyclic lipopeptide, orfamide A, is inactivated and degraded by Rhodococcus globerulus D757 and Stenotrophomonas indicatrix D763. Altogether, the demonstration that the synthetic community constrains P. protegens invasion by detoxifying its antibiotics may provide a mechanistic explanation to inconsistencies in biocontrol effectiveness in situ.

microbiology↗

Phages weaponize their bacteria with biosynthetic gene clusters

Bacteria produce many different specialized metabolites, which are encoded by biosynthetic gene clusters (BGCs). Despite high industrial relevance owing to broad bioactive potential of these metabolites, their ecological roles remain largely unexplored. We analyze all available genomes for BGCs of phage origin. The BGCs predominantly reside within temperate phages infecting certain commensal and pathogenic bacteria. Nearly all phage BGCs encode bacteriocins, which appear to serve as a strong proxy for phage specificity. Using the gut-associated bacterium Bacillus subtilis, we demonstrate how a temperate phage equips its host with a functional BGC, providing it with a competitive fitness advantage over close relatives. Therefore, certain temperate phages use BGCs to weaponize their bacteria against close relatives, leading to evolutionary benefits from lysogeny to the infected host, and hence, to the phage itself. Our study is a large step towards understanding the natural role of specialized metabolites, as well as mutualistic phage-host relationships.

microbiology↗