scholarly journals Genomic and chemical diversity of Bacillus subtilis secondary metabolites against plant pathogenic fungi

2020 ◽  
Author(s):  
Heiko T. Kiesewalter ◽  
Carlos N. Lozano-Andrade ◽  
Mario Wibowo ◽  
Mikael L. Strube ◽  
Gergely Maróti ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Mutational Analysis ◽  
Pathogenic Fungus ◽  
Pathogenic Fungi ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Biosynthetic Gene ◽  
Wide Range

ABSTRACTBacillus subtilis produces a wide range of secondary metabolites providing diverse plant-growth-promoting and biocontrol abilities. These secondary metabolites include non-ribosomal peptides (NRPs) with strong antimicrobial properties, causing either cell lysis, pore formation in fungal membranes, inhibition of certain enzymes, or bacterial protein synthesis. However, the natural products of B. subtilis are mostly studied either in laboratory strains or in individual isolates and therefore, a comparative overview of B. subtilis secondary metabolites is missing.In this study, we have isolated 23 B. subtilis strains from eleven sampling sites, compared the fungal inhibition profiles of wild types and their NRPs mutants, followed the production of targeted lipopeptides, and determined the complete genomes of 13 soil isolates. We discovered that non-ribosomal peptide production varied among B. subtilis strains co-isolated from the same soil samples. In vitro antagonism assays revealed that biocontrol properties depend on the targeted plant pathogenic fungus and the tested B. subtilis isolate. While plipastatin alone is sufficient to inhibit Fusarium sp., a combination of plipastatin and surfactin is required to hinder the growth of Botrytis cinerea. Detailed genomic analysis revealed that altered NRP production profiles in certain isolates is due to missing core genes, nonsense mutation, or potentially altered gene regulation.Our study combines microbiological antagonism assays with chemical NRPs detection and biosynthetic gene cluster predictions in diverse B. subtilis soil isolates to provide a broader overview of the secondary metabolite chemodiversity of B. subtilis.IMPORTANCESecondary or specialized metabolites with antimicrobial activities define the biocontrol properties of microorganisms. Members of the Bacillus genus produce a plethora of secondary metabolites, of which non-ribosomally produced lipopeptides in particular display strong antifungal activity. To facilitate prediction of the biocontrol potential of new Bacillus subtilis isolates, we have explored the in vitro antifungal inhibitory profiles of recent B. subtilis isolates, combined with analytical natural product chemistry, mutational analysis, and detailed genome analysis of biosynthetic gene clusters. Such a comparative analysis helped to explain why selected B. subtilis isolates lack production of certain secondary metabolites.

scholarly journals Genomic and Chemical Diversity of Bacillus subtilis Secondary Metabolites against Plant Pathogenic Fungi

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Heiko T. Kiesewalter ◽  
Carlos N. Lozano-Andrade ◽  
Mario Wibowo ◽  
Mikael L. Strube ◽  
Gergely Maróti ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Pathogenic Fungus ◽  
Gene Clusters ◽  
Chemical Diversity ◽  
Biosynthetic Gene ◽  
Nonribosomal Peptide ◽  
Content Type ◽  
Wide Range

ABSTRACT Bacillus subtilis produces a wide range of secondary metabolites providing diverse plant growth-promoting and biocontrol abilities. These secondary metabolites include nonribosomal peptides with strong antimicrobial properties, causing either cell lysis, pore formation in fungal membranes, inhibition of certain enzymes, or bacterial protein synthesis. However, the natural products of B. subtilis are mostly studied either in laboratory strains or in individual isolates, and therefore, a comparative overview of secondary metabolites from various environmental B. subtilis strains is missing. In this study, we isolated 23 B. subtilis strains from 11 sampling sites, compared the fungal inhibition profiles of wild types and their nonribosomal peptide mutants, followed the production of targeted lipopeptides, and determined the complete genomes of 13 soil isolates. We discovered that nonribosomal peptide production varied among B. subtilis strains coisolated from the same soil samples. In vitro antagonism assays revealed that biocontrol properties depend on the targeted plant pathogenic fungus and the tested B. subtilis isolate. While plipastatin alone is sufficient to inhibit Fusarium spp., a combination of plipastatin and surfactin is required to hinder growth of Botrytis cinerea. Detailed genomic analysis revealed that altered nonribosomal peptide production profiles in specific isolates are due to missing core genes, nonsense mutation, or potentially altered gene regulation. Our study combines microbiological antagonism assays with chemical nonribosomal peptide detection and biosynthetic gene cluster predictions in diverse B. subtilis soil isolates to provide a broader overview of the secondary metabolite chemodiversity of B. subtilis. IMPORTANCE Secondary or specialized metabolites with antimicrobial activities define the biocontrol properties of microorganisms. Members of the Bacillus genus produce a plethora of secondary metabolites, of which nonribosomally produced lipopeptides in particular display strong antifungal activity. To facilitate the prediction of the biocontrol potential of new Bacillus subtilis isolates, we have explored the in vitro antifungal inhibitory profiles of recent B. subtilis isolates, combined with analytical natural product chemistry, mutational analysis, and detailed genome analysis of biosynthetic gene clusters. Such a comparative analysis helped to explain why selected B. subtilis isolates lack the production of certain secondary metabolites.

scholarly journals Phylogenetic Distribution of Secondary Metabolites in the Bacillus subtilis Species Complex

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Kat Steinke ◽  
Omkar S. Mohite ◽  
Tilmann Weber ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Species Complex ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Content Type ◽  
Frameshift Mutations ◽  
Metabolite Production

ABSTRACT Microbes produce a plethora of secondary (or specialized) metabolites that, although not essential for primary metabolism, benefit them to survive in the environment, communicate, and influence cell differentiation. Biosynthetic gene clusters (BGCs), responsible for the production of these secondary metabolites, are readily identifiable on bacterial genome sequences. Understanding the phylogeny and distribution of BGCs helps us to predict the natural product synthesis ability of new isolates. Here, we examined 310 genomes from the Bacillus subtilis group, determined the inter- and intraspecies patterns of absence/presence for all BGCs, and assigned them to defined gene cluster families (GCFs). This allowed us to establish patterns in the distribution of both known and unknown products. Further, we analyzed variations in the BGC structures of particular families encoding natural products, such as plipastatin, fengycin, iturin, mycosubtilin, and bacillomycin. Our detailed analysis revealed multiple GCFs that are species or clade specific and a few others that are scattered within or between species, which will guide exploration of the chemodiversity within the B. subtilis group. Surprisingly, we discovered that partial deletion of BGCs and frameshift mutations in selected biosynthetic genes are conserved within phylogenetically related isolates, although isolated from around the globe. Our results highlight the importance of detailed genomic analysis of BGCs and the remarkable phylogenetically conserved erosion of secondary metabolite biosynthetic potential in the B. subtilis group. IMPORTANCE Members of the B. subtilis species complex are commonly recognized producers of secondary metabolites, among those, the production of antifungals, which makes them promising biocontrol strains. While there are studies examining the distribution of well-known secondary metabolites in Bacilli, intraspecies clade-specific distribution has not been systematically reported for the B. subtilis group. Here, we report the complete biosynthetic potential within the B. subtilis group to explore the distribution of the biosynthetic gene clusters and to reveal an exhaustive phylogenetic conservation of secondary metabolite production within Bacillus that supports the chemodiversity within this species complex. We identify that certain gene clusters acquired deletions of genes and particular frameshift mutations, rendering them inactive for secondary metabolite biosynthesis, a conserved genetic trait within phylogenetically conserved clades of certain species. The overview guides the assignment of the secondary metabolite production potential of newly isolated Bacillus strains based on genome sequence and phylogenetic relatedness.

scholarly journals A Two-Step Mechanism for the Activation of Actinorhodin Export and Resistance in Streptomyces coelicolor

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Ye Xu ◽  
Andrew Willems ◽  
Catherine Au-yeung ◽  
Kapil Tahlan ◽  
Justin R. Nodwell
Keyword(s):  
Secondary Metabolites ◽  
Pathogenic Bacteria ◽  
Streptomyces Coelicolor ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Resistance Mechanisms ◽  
Biosynthetic Gene ◽  
Content Type

ABSTRACT Many microorganisms produce secondary metabolites that have antibiotic activity. To avoid self-inhibition, the producing cells often encode cognate export and/or resistance mechanisms in the biosynthetic gene clusters for these molecules. Actinorhodin is a blue-pigmented antibiotic produced by Streptomyces coelicolor. The actAB operon, carried in the actinorhodin biosynthetic gene cluster, encodes two putative export pumps and is regulated by the transcriptional repressor protein ActR. In this work, we show that normal actinorhodin yields require actAB expression. Consistent with previous in vitro work, we show that both actinorhodin and its 3-ring biosynthetic intermediates [e.g., (S)-DNPA] can relieve repression of actAB by ActR in vivo. Importantly, an ActR mutant that interacts productively with (S)-DNPA but not with actinorhodin responds to the actinorhodin biosynthetic pathway with the induction of actAB and normal yields of actinorhodin. This suggests that the intermediates are sufficient to trigger the export genes in actinorhodin-producing cells. We further show that actinorhodin-producing cells can induce actAB expression in nonproducing cells; however, in this case actinorhodin is the most important signal. Finally, while the “intermediate-only” ActR mutant permits sufficient actAB expression for normal actinorhodin yields, this expression is short-lived. Sustained culture-wide expression requires a subsequent actinorhodin-mediated signaling step, and the defect in this response causes widespread cell death. These results are consistent with a two-step model for actinorhodin export and resistance where intermediates trigger initial expression for export from producing cells and actinorhodin then triggers sustained export gene expression that confers culture-wide resistance. IMPORTANCE Understanding the links between antibiotic resistance and biosynthesis is important for our efforts to manipulate secondary metabolism. For example, many secondary metabolites are produced at low levels; our work suggests that manipulating export might be one way to enhance yields of these molecules. It also suggests that understanding resistance will be relevant to the generation of novel secondary metabolites through the creation of synthetic secondary metabolic gene clusters. Finally, these cognate resistance mechanisms are related to mechanisms that arise in pathogenic bacteria, and understanding them is relevant to our ability to control microbial infections clinically.

scholarly journals In vitro Antibacterial Potential of Halophilic Bacterial Secondary Metabolites from Salted Fish

2016 ◽  
Vol 8 (04) ◽  
Author(s):  
G. Prakash Williams ◽  
Anju Anand ◽  
Parvathy A. ◽  
Rakky C. Raj ◽  
Robert Raju ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Xanthomonas Campestris ◽  
Halophilic Bacteria ◽  
Resistance Pattern ◽  
Salted Fish ◽  
Wide Range ◽  
Fish Samples

Living organisms can be found over a wide range of extreme conditions. Most of the organisms living in extreme environments (i.e, extremophiles) belong to the prokaryotes. Halophiles are interesting class of extremophilic organisms that have adapted to harsh, hypersaline conditions. They are able to compete successfully for water and resist the denaturing effects of salts. The present study was an investigation on the in vitro antibacterial effect of secondary metabolites from halophilic bacteria isolated from salted fish samples. The cured salted fish samples were collected and enumerated using halophilic Nutrient Agar supplemented with 4% NaCl. The isolated and purified bacterial cultures are numbered as SF1, SF2, SF3, SF4 and SF5 are further identified using VITEK 2 system as Bacillus vallismortis, Ralstonia mannitolytica, Bacillus subtilis, Rhizoboum radiobacter and Kocuria kristina. Growth kinetics of halobacterial isolates were determined by spectrophotometric assay. The antibiotic resistance pattern of tested pathogenic microorganisms using the commercial antibiotics was screened and almost all the tested microorganisms are resistant to Penicillin. The antimicrobial activity of secondary metabolites of halophilic bacteria against drug resistant microbes was assessed using the Agar well diffusion assay. Among the different extracts of the halophilic bacteria, the chloroform extracts of R. mannitolytica showed maximum antibacterial activity against Bacillus subtilis MTCC 441 and Xanthomonas campestris MTCC 2286. The results of antimicrobial activity are considerable because it enables the identification of potential secondary metabolites present in marine halophilic bacteria, which act as source of innumerable therapeutic agents. Further research is highly warranted to find out the active principle responsible for the antibacterial property and to elucidate the structure of particular compound.

scholarly journals Reconstitution of polythioamide antibiotic backbone formation reveals unusual thiotemplated assembly strategy

2020 ◽  
Vol 117 (16) ◽  
pp. 8850-8858
Author(s):  
Kyle L. Dunbar ◽  
Maria Dell ◽  
Finn Gude ◽  
Christian Hertweck
Keyword(s):  
Secondary Metabolites ◽  
Anaerobic Bacteria ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Peptide Backbone ◽  
Nonribosomal Peptide ◽  
Bacterial Phyla ◽  
Biochemical Assays

Closthioamide (CTA) is a rare example of a thioamide-containing nonribosomal peptide and is one of only a handful of secondary metabolites described from obligately anaerobic bacteria. Although the biosynthetic gene cluster responsible for CTA production and the thioamide synthetase that catalyzes sulfur incorporation were recently discovered, the logic for peptide backbone assembly has remained a mystery. Here, through the use of in vitro biochemical assays, we demonstrate that the amide backbone of CTA is assembled in an unusual thiotemplated pathway involving the cooperation of a transacylating member of the papain-like cysteine protease family and an iteratively acting ATP-grasp protein. Using the ATP-grasp protein as a bioinformatic handle, we identified hundreds of such thiotemplated yet nonribosomal peptide synthetase (NRPS)-independent biosynthetic gene clusters across diverse bacterial phyla. The data presented herein not only clarify the pathway for the biosynthesis of CTA, but also provide a foundation for the discovery of additional secondary metabolites produced by noncanonical biosynthetic pathways.

scholarly journals SeMPI 2.0—A Web Server for PKS and NRPS Predictions Combined with Metabolite Screening in Natural Product Databases

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 13
Author(s):  
Paul F. Zierep ◽  
Adriana T. Ceci ◽  
Ilia Dobrusin ◽  
Sinclair C. Rockwell-Kollmann ◽  
Stefan Günther
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Building Block ◽  
Web Server ◽  
Gene Clusters ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
A Genome ◽  
Wide Range

Microorganisms produce secondary metabolites with a remarkable range of bioactive properties. The constantly increasing amount of published genomic data provides the opportunity for efficient identification of biosynthetic gene clusters by genome mining. On the other hand, for many natural products with resolved structures, the encoding biosynthetic gene clusters have not been identified yet. Of those secondary metabolites, the scaffolds of nonribosomal peptides and polyketides (type I modular) can be predicted due to their building block-like assembly. SeMPI v2 provides a comprehensive prediction pipeline, which includes the screening of the scaffold in publicly available natural compound databases. The screening algorithm was designed to detect homologous structures even for partial, incomplete clusters. The pipeline allows linking of gene clusters to known natural products and therefore also provides a metric to estimate the novelty of the cluster if a matching scaffold cannot be found. Whereas currently available tools attempt to provide comprehensive information about a wide range of gene clusters, SeMPI v2 aims to focus on precise predictions. Therefore, the cluster detection algorithm, including building block generation and domain substrate prediction, was thoroughly refined and benchmarked, to provide high-quality scaffold predictions. In a benchmark based on 559 gene clusters, SeMPI v2 achieved comparable or better results than antiSMASH v5. Additionally, the SeMPI v2 web server provides features that can help to further investigate a submitted gene cluster, such as the incorporation of a genome browser, and the possibility to modify a predicted scaffold in a workbench before the database screening.

scholarly journals Differential regulation and production of secondary metabolites among isolates of the fungal wheat pathogen Zymoseptoria tritici

2021 ◽  
Author(s):  
M. Amine Hassani ◽  
Ernest Oppong-Danquah ◽  
Alice Feurty ◽  
Deniz Tasdemir ◽  
Eva H Stukenbrock
Keyword(s):  
Secondary Metabolites ◽  
Secondary Metabolite ◽  
Expression Profiles ◽  
Pathogenic Fungus ◽  
Gene Clusters ◽  
Secondary Metabolite Production ◽  
Zymoseptoria Tritici ◽  
Host Colonization ◽  
Metabolite Production

The genome of the wheat pathogenic fungus, Zymoseptoria tritici, represents extensive presence-absence variation in gene content. Here, we addressed variation in biosynthetic gene clusters (BGCs) content and biochemical profiles among three isolates. We analysed secondary metabolite properties based on genome, transcriptome and metabolome data. The isolates represent highly distinct genome architecture, but harbor similar repertoire of BGCs. Expression profiles for most BGCs show comparable patterns of regulation among the isolates, suggesting a conserved 'biochemical infection program'. For all three isolates, we observed a strong up-regulation of an abscisic acid (ABA) gene cluster during biotrophic host colonization, indicating that Z. tritici potentially interfere with host defenses by the biosynthesis of this phytohormone. Further, during in vitro growth the isolates show similar metabolomes congruent with the predicted BGC content. We assessed if secondary metabolite production is regulated by histone methylation using a mutant impaired in formation of facultative heterochromatin (H3K27me3). In contrast to other ascomycete fungi, chromatin modifications play a less prominent role in regulation of secondary metabolites. In summary, we show that Z. tritici has a conserved program of secondary metabolite production contrasting the immense variation in effector expression, some of these metabolites might play a key role during host colonization.

scholarly journals Secondary Metabolites Production by Actinomycetes and their Antifungal Activity

2017 ◽  
Vol 3 (4) ◽  
pp. 256 ◽  
Author(s):  
Tirta Kumala Dewi ◽  
Dwi Agustiani ◽  
Sarjiya Antonius
Keyword(s):  
Antifungal Activity ◽  
Secondary Metabolites ◽  
Thin Layer ◽  
Fusarium Oxysporum ◽  
Thin Layer Chromatography ◽  
Pathogenic Fungi ◽  
Diffusion Method ◽  
Wide Range ◽  
Layer Chromatography

<p class="Els-Abstract-text">Wilt desease of banana caused by <em>Fusarium oxysporum</em> f.sp. <em>cubense</em> (FOC) is one of the most destructive deseases of banana in the tropics. Actinomycetes are the most economically and biotechnologically valuable prokaryotes able to produce wide range of bioactive secondary metabolites. The aims of the present study are to isolate and screen the actinomycetes with high potential ability to produce secondary metabolites that have inhibitory activity against plant pathogenic fungi, <em>Fusarium oxysporum</em> f. sp. <em>cubense</em>. Two isolates from Lampung and Cianjur showed activity against fungi. The isolates designed as L.3.1 and CiIA5b. The metabolites from potent stain was produced by extraction of culture filtrate with ethyl acetate : methanol (4:1), it was tested for their antifungal activity by well diffusion method. Evidence for in vitro antibiosis of L.3.1 and CiIA5b isolates was demonstrated by the zone of fungal-growth inhibition. Production of secondary metabolites was analysis by thin layer chromatography (TLC) and bioautography assays. In this study, the metabolites from L.3.1 and CiIA5b have showed good antifungal activity.</p><div><p class="Els-keywords"><em> </em></p><p class="Els-keywords"><strong>Keywords:</strong> Actinomycetes; antifungal activity; bioautography; secondary metabolites; thin layer chromatography.</p></div>

scholarly journals Phylogenetic distribution of secondary metabolites in the Bacillus subtilis species complex

2020 ◽  
Author(s):  
Kat Steinke ◽  
Omkar S. Mohite ◽  
Tilmann Weber ◽  
Ákos T. Kovács
Keyword(s):  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Detailed Analysis ◽  
Secondary Metabolite ◽  
Genome Sequence ◽  
Species Complex ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Metabolite Production

ABSTRACTMicrobes produce a plethora of secondary metabolites that although not essential for primary metabolism benefit them to survive in the environment, communicate, and influence differentiation. Biosynthetic gene clusters (BGCs) responsible for the production of these secondary metabolites are readily identifiable on the genome sequence of bacteria. Understanding the phylogeny and distribution of BGCs helps us to predict natural product synthesis ability of new isolates. Here, we examined the inter- and intraspecies patterns of absence/presence for all BGCs identified with antiSMASH 5.0 in 310 genomes from the B. subtilis group and assigned them to defined gene cluster families (GCFs). This allowed us to establish patterns in distribution for both known and unknown products. Further, we analyzed variations in the BGC structure of particular families encoding for natural products such as plipastatin, fengycin, iturin, mycosubtilin and bacillomycin. Our detailed analysis revealed multiple GCFs that are species or clade specific and few others that are scattered within or between species, which will guide exploration of the chemodiversity within the B. subtilis group. Uniquely, we discovered that partial deletion of BGCs and frameshift mutations in selected biosynthetic genes are conserved within phylogenetically related isolates, although isolated from around the globe. Our results highlight the importance of detailed analysis of BGCs and the remarkable phylogenetically conserved errodation of secondary metabolite biosynthetic potential in the B. subtilis group.IMPORTANCEMembers of the B. subtilis species complex are commonly recognized producers of secondary metabolites, among those the production of antifungals makes them promising biocontrol strains. However, while there are studies examining the distribution of well-known B. subtilis metabolites, this has not yet been systematically reported for the group. Here, we report the complete biosynthetic potential within the Bacillus subtilis group species to explore the distribution of the biosynthetic gene clusters and to provide an exhaustive phylogenetic conservation of secondary metabolite production supporting the chemodiversity of Bacilli. We identify that certain gene clusters acquired deletions of genes and particular frame-shift mutations rendering them inactive for secondary metabolite biosynthesis, a conserved genetic trait within phylogenetically conserved clades of certain species. The overview presented will superbly guide assigning the secondary metabolite production potential of newly isolated strains based on genome sequence and phylogenetic relatedness.

scholarly journals Thiopeptide antibiotics stimulate biofilm formation in Bacillus subtilis

2015 ◽  
Vol 112 (10) ◽  
pp. 3086-3091 ◽  
Author(s):  
Rachel Bleich ◽  
Jeramie D. Watrous ◽  
Pieter C. Dorrestein ◽  
Albert A. Bowers ◽  
Elizabeth A. Shank
Keyword(s):  
Natural Products ◽  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Bacterial Species ◽  
Imaging Mass Spectrometry ◽  
Gene Clusters ◽  
Peptide Antibiotics ◽  
Wide Range ◽  
Thiopeptide Antibiotics ◽  
Peptide Gene

Bacteria have evolved the ability to produce a wide range of structurally complex natural products historically called “secondary” metabolites. Although some of these compounds have been identified as bacterial communication cues, more frequently natural products are scrutinized for antibiotic activities that are relevant to human health. However, there has been little regard for how these compounds might otherwise impact the physiology of neighboring microbes present in complex communities. Bacillus cereus secretes molecules that activate expression of biofilm genes in Bacillus subtilis. Here, we use imaging mass spectrometry to identify the thiocillins, a group of thiazolyl peptide antibiotics, as biofilm matrix-inducing compounds produced by B. cereus. We found that thiocillin increased the population of matrix-producing B. subtilis cells and that this activity could be abolished by multiple structural alterations. Importantly, a mutation that eliminated thiocillin’s antibiotic activity did not affect its ability to induce biofilm gene expression in B. subtilis. We go on to show that biofilm induction appears to be a general phenomenon of multiple structurally diverse thiazolyl peptides and use this activity to confirm the presence of thiazolyl peptide gene clusters in other bacterial species. Our results indicate that the roles of secondary metabolites initially identified as antibiotics may have more complex effects—acting not only as killing agents, but also as specific modulators of microbial cellular phenotypes.

Sign in / Sign up

Export Citation Format

Share Document