Horizontal transfer of bacteriocin biosynthesis genes requires metabolic adaptation to improve compound production and cellular fitness
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA857994 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20124487.fastq.gz | Fastqsanger.gz | |||
| SRR20124488.fastq.gz | Fastqsanger.gz | |||
| SRR20124489.fastq.gz | Fastqsanger.gz | |||
| SRR20124490.fastq.gz | Fastqsanger.gz | |||
| SRR20124491.fastq.gz | Fastqsanger.gz |
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Project description:<p>Biosynthetic gene clusters (BGCs) encoding the production of bacteriocins are widespread among bacterial isolates and are important genetic determinants of competitive fitness within a given habitat. Staphylococci produce a tremendous diversity of compounds, and the corresponding BGCs are frequently associated with mobile genetic elements, suggesting gain and loss of biosynthetic capacity. Pharmaceutical biology has shown that compound production in heterologous hosts is often challenging, and many BGC recipients initially produce small amounts of compound or show reduced growth rates. To assess whether transfer of BGCs between closely related Staphylococcus aureus strains can be instantly effective or requires elaborate metabolic adaptation, we investigated the intraspecies transfer of a BGC encoding the ribosomally synthesized and posttranslationally modified peptide (RiPP) micrococcin P1 (MP1). We found that acquisition of the BGC by S. aureus RN4220 enabled immediate MP1 production but also imposed a metabolic burden, which was relieved after prolonged cultivation by adaptive mutation. We used a multiomics approach to study this phenomenon and found adaptive evolution to select for strains with increased activity of the tricarboxylic acid cycle (TCA), which enhanced metabolic fitness and levels of compound production. Metabolome analysis revealed increases of central metabolites, including citrate and α-ketoglutarate in the adapted strain, suggesting metabolic adaptation to overcome the BGC-associated growth defects. Our results indicate that BGC acquisition requires genetic and metabolic predispositions, allowing the integration of bacteriocin production into the cellular metabolism. Inappropriate metabolic characteristics of recipients can entail physiological burdens, negatively impacting the competitive fitness of recipients within natural bacterial communities.</p><p><strong>IMPORTANCE:</strong> Human microbiomes are critically associated with human health and disease. Importantly, pathogenic bacteria can hide in human-associated communities and can cause disease when the composition of the community becomes unbalanced. Bacteriocin-producing commensals are able to displace pathogens from microbial communities, suggesting that their targeted introduction into human microbiomes might prevent pathogen colonization and infection. However, to develop probiotic approaches, strains are needed that produce high levels of bioactive compounds and retain cellular fitness within mixed bacterial communities. Our work offers insights into the metabolic burdens associated with the production of the bacteriocin micrococcin P1 and highlights evolutionary strategies that increase cellular fitness in the context of production. Metabolic adaptations are most likely broadly relevant for bacteriocin producers and need to be considered for the future development of effective microbiome editing strategies.</p>
2022-11-09 | MTBLS5196 | MetaboLights
Project description:Biosynthetic gene clusters (BGCs) encoding the production of bacteriocins are widespread amongst bacterial isolates and are important genetic determinants of competitive fitness among bacterial lineages within a given habitat. Staphylococci produce a tremendous diversity of compounds and the corresponding gene clusters (Staphylococcal Antibiosis Islands - SAbIs) are frequently associated with mobile genetic elements, suggesting acquisition and loss of biosynthetic capacity. Pharmaceutical biology has shown that compound production in heterologous hosts is often challenged by the lack of optimal precursor supplies. Accordingly, many recipients produce low compound amounts or show reduced growth rates. To assess whether transfer of SAbIs between closely related S. aureus strains has similar effects, we used as model the SAbI encoding the ribosomally synthesized and post-translationally modified peptide (RiPP) Micrococcin P1 (MP1). We found that acquisition of the SAbI by S. aureus RN4220 did allow immediate MP1 production but also imposed a metabolic burden. Adaptive evolution selected for strains with increased TCA-cycle activity, which enhanced metabolic fitness and levels of compound production. Metabolome analysis showed that the adaptive mutation increased the levels of central metabolites including citrate and α-ketoglutarate, and the increased availability of citrate turned out to be essential to overcome SAbI associated growth defects. Our results indicate that acquisition of SAbIs represents a blessing for the recipient strain as long as its genetic and metabolic predispositions allow integration of bacteriocin production into the cellular metabolism. This in turn may be crucial to ensure the competitive fitness of SAbI recipients within natural bacterial communities.
2022-11-21 | GSE208001 | GEO
Project description:Biosynthetic gene clusters (BGCs) encoding the production of bacteriocins are widespread among bacterial isolates and are important genetic determinants of competitive fitness within a given habitat. Staphylococci produce a tremendous diversity of compounds, and the corresponding BGCs are frequently associated with mobile genetic elements, suggesting gain and loss of biosynthetic capacity. Pharmaceutical biology has shown that compound production in heterologous hosts is often challenging, and many BGC recipients initially produce small amounts of compound or show reduced growth rates. To assess whether transfer of BGCs between closely related Staphylococcus aureus strains can be instantly effective or requires elaborate metabolic adaptation, we investigated the intraspecies transfer of a BGC encoding the ribosomally synthesized and posttranslationally modified peptide (RiPP) micrococcin P1 (MP1). We found that acquisition of the BGC by S. aureus RN4220 enabled immediate MP1 production but also imposed a metabolic burden, which was relieved after prolonged cultivation by adaptive mutation. We used a multiomics approach to study this phenomenon and found adaptive evolution to select for strains with increased activity of the tricarboxylic acid cycle (TCA), which enhanced metabolic fitness and levels of compound production. Metabolome analysis revealed increases of central metabolites, including citrate and α-ketoglutarate in the adapted strain, suggesting metabolic adaptation to overcome the BGC-associated growth defects. Our results indicate that BGC acquisition requires genetic and metabolic predispositions, allowing the integration of bacteriocin production into the cellular metabolism. Inappropriate metabolic characteristics of recipients can entail physiological burdens, negatively impacting the competitive fitness of recipients within natural bacterial communities. IMPORTANCE Human microbiomes are critically associated with human health and disease. Importantly, pathogenic bacteria can hide in human-associated communities and can cause disease when the composition of the community becomes unbalanced. Bacteriocin-producing commensals are able to displace pathogens from microbial communities, suggesting that their targeted introduction into human microbiomes might prevent pathogen colonization and infection. However, to develop probiotic approaches, strains are needed that produce high levels of bioactive compounds and retain cellular fitness within mixed bacterial communities. Our work offers insights into the metabolic burdens associated with the production of the bacteriocin micrococcin P1 and highlights evolutionary strategies that increase cellular fitness in the context of production. Metabolic adaptations are most likely broadly relevant for bacteriocin producers and need to be considered for the future development of effective microbiome editing strategies.
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Project description:Plasmid fitness is directed by two orthogonal processes—vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff that constrains plasmid evolution. Here we present evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical E. coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.
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Project description:Horizontal transfer of plasmids is one of the main drivers of bacterial adaptation, resulting e.g. in the spread of antibiotic resistance. We investigated the marine Roseobacter group and studied how conjugation affects the gene expression and biology of the new host. We showed that the two syntenic 126 kb and 191 kb plasmids of Dinoroseobacter shibae can be conjugated into representatives of all major lineages of Rhodobacteraceae. In the model organism Phaeobacter inhibens their acquisition resulted in differential expression of genes related to motility, transport and the synthesis of vitamins. Moreover, the decrease of the potent antibiotic tropodithietic acid reduced the energetic burden of Phaeobacter and resulted in an enhanced growth. While the T4SS systems of both plasmids were silenced in the new host, the ability to kill the dinoflagellate was exclusively transferred via the 191 kb plasmid from D. shibae to P. inhibens. Our findings showed drastic consequences of plasmid conjugation; genetic reprogramming of the novel host resulted in considerable fitness changes leading to the prediction that horizontal gene transfer triggers bacterial speciation.
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Project description:Antibiotic resistance is exacerbated by the exchange of antibiotic resistance genes (ARGs) between microbes from diverse habitats. Plasmids are important ARGs mobile elements and are spread by horizontal gene transfer (HGT). In this study, we demonstrated the presence of multi-resistant plasmids from inhalable particulate matter (PM) and its effect on gene horizontal transfer. Three transferable multi-resistant plasmids were identified from PM in a hospital, using conjugative mating assays and nanopore sequencing. pTAir-3 contained 26 horizontal transfer elements and 10 ARGs. Importantly pTAir-5 harbored carbapenem resistance gene (blaOXA) which shows homology to plasmids from human and pig commensal bacteria, thus indicating that PM is a media for antibiotic resistant plasmid spread. In addition, 125 μg/mL PM2.5 and PM10 significantly increased the conjugative transfer rate by 110% and 30%, respectively, and augmented reactive oxygen species (ROS) levels. Underlying mechanisms were revealed by identifying the upregulated expressional levels of genes related to ROS, SOS, cell membranes, pilus generation, and transposition via genome-wide RNA sequencing. The study highlights the airborne spread of multi-resistant plasmids and the impact of inhalable PM on the horizontal transfer of antibiotic resistance.
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