Dataset Information

Genome analysis of secondary metabolite‑biosynthetic gene clusters of Photorhabdus akhurstii subsp. akhurstii and its antibacterial activity against antibiotic-resistant bacteria.

ABSTRACT: Xenorhabdus and Photorhabdus can produce a variety of secondary metabolites with broad spectrum bioactivity against microorganisms. We investigated the antibacterial activity of Xenorhabdus and Photorhabdus against 15 antibiotic-resistant bacteria strains. Photorhabdus extracts had strong inhibitory the growth of Methicillin-resistant Staphylococcus aureus (MRSA) by disk diffusion. The P. akhurstii s subsp. akhurstii (bNN168.5_TH) extract showed lower minimum inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC). The interaction between either P. akhurstii subsp. akhurstii (bNN141.3_TH) or P. akhurstii subsp. akhurstii (bNN168.5_TH) or P. hainanensis (bNN163.3_TH) extract in combination with oxacillin determined by checkerboard assay exhibited partially synergistic interaction with fractional inhibitory concentration index (FICI) of 0.53. Time-killing assay for P. akhurstii subsp. akhurstii (bNN168.5_TH) extract against S. aureus strain PB36 significantly decreased cell viability from 105 CFU/ml to 103 CFU/ml within 30 min (P < 0.001, t-test). Transmission electron microscopic investigation elucidated that the bNN168.5_TH extract caused treated S. aureus strain PB36 (MRSA) cell membrane damage. The biosynthetic gene clusters of the bNN168.5_TH contained non-ribosomal peptide synthetase cluster (NRPS), hybrid NRPS-type l polyketide synthase (PKS) and siderophore, which identified potentially interesting bioactive products: xenematide, luminmide, xenortide A-D, luminmycin A, putrebactin/avaroferrin and rhizomide A-C. This study demonstrates that bNN168.5_TH showed antibacterial activity by disrupting bacterial cytoplasmic membrane and the draft genome provided insights into the classes of bioactive products. This also provides a potential approach in developing a novel antibacterial agent.

SUBMITTER: Muangpat P

PROVIDER: S-EPMC9491552 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Genome analysis of secondary metabolite‑biosynthetic gene clusters of Photorhabdus akhurstii subsp. akhurstii and its antibacterial activity against antibiotic-resistant bacteria.

Muangpat Paramaporn P Meesil Wipanee W Ngoenkam Jatuporn J Teethaisong Yothin Y Thummeepak Rapee R Sitthisak Sutthirat S Tandhavanant Sarunporn S Chantratita Narisara N Bode Helge B HB Vitta Apichat A Thanwisai Aunchalee A

PloS one 20220921 9

Xenorhabdus and Photorhabdus can produce a variety of secondary metabolites with broad spectrum bioactivity against microorganisms. We investigated the antibacterial activity of Xenorhabdus and Photorhabdus against 15 antibiotic-resistant bacteria strains. Photorhabdus extracts had strong inhibitory the growth of Methicillin-resistant Staphylococcus aureus (MRSA) by disk diffusion. The P. akhurstii s subsp. akhurstii (bNN168.5_TH) extract showed lower minimum inhibitory concentrations (MIC) and ...[more]

PMID: 36129957

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Project description:Recent reviews have reinforced sponge-associated bacteria as a valuable source of structurally diverse secondary metabolites with potent biological properties, which makes these microbial communities promising sources of new drug candidates. However, the overall diversity of secondary metabolite biosynthetic potential present in bacteria is difficult to access due to the fact that the majority of bacteria are not readily cultured in the laboratory. Thus, use of cultivation-independent approaches may allow accessing "silent" and "cryptic" secondary metabolite biosynthetic gene clusters present in bacteria that cannot yet be cultured. In the present study, we investigated the diversity of secondary metabolite biosynthetic gene clusters (BGCs) in metagenomes of bacterial communities associated with three sponge species: Clathria reinwardti, Rhabdastrella globostellata, and Spheciospongia sp. The results reveal that the three metagenomes contain a high number of predicted BGCs, ranging from 282 to 463 BGCs per metagenome. The types of BGCs were diverse and represented 12 different cluster types. Clusters predicted to encode fatty acid synthases and polyketide synthases (PKS) were the most dominant BGC types, followed by clusters encoding synthesis of terpenes and bacteriocins. Based on BGC sequence similarity analysis, 363 gene cluster families (GCFs) were identified. Interestingly, no GCFs were assigned to pathways responsible for the production of known compounds, implying that the clusters detected might be responsible for production of several novel compounds. The KS gene sequences from PKS clusters were used to predict the taxonomic origin of the clusters involved. The KS sequences were related to 12 bacterial phyla with Actinobacteria, Proteobacteria, and Firmicutes as the most predominant. At the genus level, the KSs were most related to those found in the genera Mycolicibacterium, Mycobacterium, Burkholderia, and Streptomyces. Phylogenetic analysis of KS sequences resulted in detection of two known 'sponge-specific' BGCs, i.e., SupA and SwfA, as well as a new 'sponge-specific' cluster related to fatty acid synthesis in the phylum Candidatus Poribacteria and composed only by KS sequences of the three sponge-associated bacterial communities assessed here.

Project description:Mesophotic coral ecosystems (MCEs) host a diverse array of sponge species, which represent a promising source of bioactive compounds. Increasing evidence suggests that sponge-associated bacteria may be the primary producers of these compounds. However, cultivating these bacteria under laboratory conditions remains a significant challenge. To investigate the rich resource of bioactive compounds synthesised by mesophotic sponge-associated bacteria, we retrieved 429 metagenome-assembled genomes (MAGs) from 15 mesophotic sponges, revealing a strong correlation between bacterial diversity and sponge species. Furthermore, we identified 1637 secondary metabolite biosynthetic gene clusters (BGCs) within these MAGs. Among the identified BGCs, terpenes were the most abundant (495), followed by 369 polyketide synthases (PKSs), 293 ribosomally synthesised and post-translationally modified peptides (RiPPs) and 135 nonribosomal peptide synthetases (NRPSs). The BGCs were classified into 1086 gene cluster families (GCFs) based on sequence similarity. Notably, only five GCFs included experimentally validated reference BGCs from the Minimum Information about a Biosynthetic Gene cluster database (MIBiG). Additionally, an unusual abundance of BGCs was detected in Entotheonella sp. (s191209.Bin93) from the Tectomicrobia phylum. In contrast, members of Proteobacteria and Acidobacteriota harboured fewer BGCs (6-7 on average), yet their high abundance in MCE sponges suggests a potentially rich reservoir of BGCs. Analysis of the BGC distribution patterns revealed that a subset of BGCs, including terpene GCFs (FAM_00447 and FAM_01046), PKS GCF (FAM_00235), and RiPPs GCF (FAM_01143), were widespread across mesophotic sponges. Furthermore, 32 GCFs were consistently present in the same MAGs across different sponges, highlighting their potential key biological roles and capacity to yield novel bioactive compounds. This study not only underscores the untapped potential of mesophotic sponge-associated bacteria as a source of bioactive compounds but also provides valuable insights into the intricate interactions between sponges and their symbiotic microbial communities.

Dataset Information

Genome analysis of secondary metabolite‑biosynthetic gene clusters of Photorhabdus akhurstii subsp. akhurstii and its antibacterial activity against antibiotic-resistant bacteria.

Publications

Genome analysis of secondary metabolite‑biosynthetic gene clusters of Photorhabdus akhurstii subsp. akhurstii and its antibacterial activity against antibiotic-resistant bacteria.

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