scholarly journals Redox-active secondary metabolites act as interspecies modulators of antibiotic resilience

2021 ◽  
Author(s):  
Lucas A. Meirelles ◽  
Dianne K. Newman
Keyword(s):  
Secondary Metabolites ◽  
Burkholderia Cepacia ◽  
Defense Responses ◽  
Microbial Interactions ◽  
Opportunistic Pathogens ◽  
Burkholderia Gladioli ◽  
Redox Active ◽  
Wide Range ◽  
Genes Encoding

ABSTRACTBacterial opportunistic pathogens make a wide range of secondary metabolites both in the natural environment and when causing infections, yet how these molecules mediate microbial interactions and their consequences for antibiotic treatment are still poorly understood. Here, we explore the role of two redox-active secondary metabolites, pyocyanin and toxoflavin, as interspecies modulators of antibiotic resilience. We find that these molecules dramatically change susceptibility levels of diverse bacteria to clinical antibiotics. Pyocyanin is made by Pseudomonas aeruginosa, while toxoflavin is made by Burkholderia gladioli, organisms that infect cystic fibrosis and other immunocompromised patients. Both molecules alter the susceptibility profile of pathogenic species within the “Burkholderia cepacia complex” to different antibiotics, either antagonizing or potentiating their effects, depending on the drug’s class. Defense responses regulated by the redox-sensitive transcription factor SoxR potentiate the antagonistic effects these metabolites have against fluoroquinolones, and the presence of genes encoding SoxR and the efflux systems it regulates can be used to predict how these metabolites will affect antibiotic susceptibility of different bacteria. Finally, we demonstrate that inclusion of secondary metabolites in standard protocols used to assess antibiotic resistance can dramatically alter the results, motivating the development of new tests for more accurate clinical assessment.

scholarly journals The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Defense Responses ◽  
C Elegans ◽  
Host Immune Responses ◽  
Wide Range ◽  
Independent Functions ◽  
Multiple Cell

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

scholarly journals Expression of Type IV Pili by Moraxella catarrhalis Is Essential for Natural Competence and Is Affected by Iron Limitation

2004 ◽  
Vol 72 (11) ◽  
pp. 6262-6270 ◽  
Author(s):  
Nicole R. Luke ◽  
Amy J. Howlett ◽  
Jianqiang Shao ◽  
Anthony A. Campagnari
Keyword(s):  
Moraxella Catarrhalis ◽  
Pathogenic Bacteria ◽  
Type Iv Pili ◽  
Protein Subunit ◽  
Electron Microscopic ◽  
Type Iv ◽  
Wide Range ◽  
Genes Encoding ◽  
Microscopic Studies

ABSTRACT Type IV pili, filamentous surface appendages primarily composed of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Although previous electron microscopic studies suggested that pili might be present on the surface of Moraxella catarrhalis isolates, detailed molecular and phenotypic analyses of these structures have not been reported to date. We identified and cloned the M. catarrhalis genes encoding PilA, the major pilin subunit, PilQ, the outer membrane secretin through which the pilus filament is extruded, and PilT, the NTPase that mediates pilin disassembly and retraction. To initiate investigation of the role of this surface organelle in pathogenesis, isogenic pilA, pilT, and pilQ mutants were constructed in M. catarrhalis strain 7169. Comparative analyses of the wild-type 7169 strain and three isogenic pil mutants demonstrated that M. catarrhalis expresses type IV pili that are essential for natural genetic transformation. Our studies suggest type IV pilus production by M. catarrhalis is constitutive and ubiquitous, although pilin expression was demonstrated to be iron responsive and Fur regulated. These data indicate that additional studies aimed at elucidating the prevalence and role of type IV pili in the pathogenesis and host response to M. catarrhalis infections are warranted.

scholarly journals Distinguishing Species of the Burkholderia cepacia Complex and Burkholderia gladioli by Automated Ribotyping

2000 ◽  
Vol 38 (5) ◽  
pp. 1876-1884 ◽  
Author(s):  
Sylvain Brisse ◽  
Cees M. Verduin ◽  
Dana Milatovic ◽  
Ad Fluit ◽  
Jan Verhoef ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Burkholderia Cepacia Complex ◽  
Opportunistic Pathogens ◽  
Burkholderia Gladioli ◽  
Microbial Characterization ◽  
Automated Ribotyping ◽  
Level Cluster ◽  
Identification Analysis ◽  
Epidemiological Characterization

Several species belonging to the genus Burkholderia are clinically relevant, opportunistic pathogens that inhabit major environmental reservoirs. Consequently, the availability of means for adequate identification and epidemiological characterization of individual environmental or clinical isolates is mandatory. In the present communication we describe the use of the Riboprinter microbial characterization system (Qualicon, Warwick, United Kingdom) for automated ribotyping of 104 strains of Burkholderia species from diverse sources, including several publicly accessible collections. The main outcome of this analysis was that all strains were typeable and that strains of Burkholderia gladioli and of each species of the B. cepacia complex, includingB. multivorans, B. stabilis, and B. vietnamiensis, were effectively discriminated. Furthermore, different ribotypes were discerned within each species. Ribotyping results were in general agreement with strain classification based on restriction fragment analysis of 16S ribosomal amplicons, but the resolution of ribotyping was much higher. This enabled automated molecular typing below the species level. Cluster analysis of the patterns obtained by ribotyping (riboprints) showed that withinB. gladioli, B. multivorans, and B. cepacia genomovar VI, the different riboprints identified always clustered together. Riboprints of B. cepacia genomovars I and III, B. stabilis, and B. vietnamiensis did not show distinct clustering but rather exhibited the formation of loose assemblages within which several smaller, genomovar-specific clusters were delineated. Therefore, ribotyping proved useful for genomovar identification. Analysis of serial isolates from individual patients demonstrated that infection with a single ribotype had occurred, despite minor genetic differences that were detected by pulsed-field gel electrophoresis of DNA macrorestriction fragments. The automated approach allows very rapid and reliable identification and epidemiological characterization of strains and generates an easily manageable database suited for expansion with information on additional bacterial isolates.

scholarly journals Coral-associated micro-organisms and their roles in promoting coral health and thwarting diseases

2013 ◽  
Vol 280 (1755) ◽  
pp. 20122328 ◽  
Author(s):  
Cory J. Krediet ◽  
Kim B. Ritchie ◽  
Valerie J. Paul ◽  
Max Teplitski
Keyword(s):  
Cell Signalling ◽  
Taxonomic Diversity ◽  
Microbial Interactions ◽  
Opportunistic Pathogens ◽  
Functional Capabilities ◽  
Evolutionarily Conserved ◽  
Coral Health ◽  
Micro Organisms

Over the last decade, significant advances have been made in characterization of the coral microbiota. Shifts in its composition often correlate with the appearance of signs of diseases and/or bleaching, thus suggesting a link between microbes, coral health and stability of reef ecosystems. The understanding of interactions in coral-associated microbiota is informed by the on-going characterization of other microbiomes, which suggest that metabolic pathways and functional capabilities define the ‘core’ microbiota more accurately than the taxonomic diversity of its members. Consistent with this hypothesis, there does not appear to be a consensus on the specificity in the interactions of corals with microbial commensals, even though recent studies report potentially beneficial functions of the coral-associated bacteria. They cycle sulphur, fix nitrogen, produce antimicrobial compounds, inhibit cell-to-cell signalling and disrupt virulence in opportunistic pathogens. While their beneficial functions have been documented, it is not certain whether or how these microbes are selected by the hosts. Therefore, understanding the role of innate immunity, signal and nutrient exchange in the establishment of coral microbiota and in controlling its functions will probably reveal ancient, evolutionarily conserved mechanisms that dictate the outcomes of host–microbial interactions, and impact the resilience of the host.

scholarly journals Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism

2017 ◽  
Vol 114 (4) ◽  
pp. E560-E569 ◽  
Author(s):  
Christian Derntl ◽  
Bernhard Kluger ◽  
Christoph Bueschl ◽  
Rainer Schuhmacher ◽  
Robert L. Mach ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Secondary Metabolism ◽  
Plant Pathogens ◽  
Primary Metabolism ◽  
Sequencing Analysis ◽  
Colletotrichum Graminicola ◽  
Major Interest ◽  
Wide Range

Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei. Xpp1 was previously described as a repressor of xylanases. Here, we provide data from an RNA-sequencing analysis suggesting that Xpp1 is an activator of primary metabolism. This finding is supported by our results from a Biolog assay determining the carbon source assimilation behavior of an xpp1 deletion strain. Furthermore, the role of Xpp1 as a repressor of secondary metabolism is shown by gene expression analyses of polyketide synthases and the determination of the secondary metabolites of xpp1 deletion and overexpression strains using an untargeted metabolomics approach. The deletion of Xpp1 resulted in the enhanced secretion of secondary metabolites in terms of diversity and quantity. Homologs of Xpp1 are found among a broad range of fungi, including the biocontrol agent Trichoderma atroviride, the plant pathogens Fusarium graminearum and Colletotrichum graminicola, the model organism Neurospora crassa, the human pathogen Sporothrix schenckii, and the ergot fungus Claviceps purpurea.

scholarly journals Distribution of Cepacian Biosynthesis Genes among Environmental and Clinical Burkholderia Strains and Role of Cepacian Exopolysaccharide in Resistance to Stress Conditions

2009 ◽  
Vol 76 (2) ◽  
pp. 441-450 ◽  
Author(s):  
Ana S. Ferreira ◽  
Jorge H. Leitão ◽  
Inês N. Silva ◽  
Pedro F. Pinheiro ◽  
Sílvia A. Sousa ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Metal Ion ◽  
Repeat Unit ◽  
Growth Promoters ◽  
Gene Encoding ◽  
Reverse Transcription Pcr ◽  
Plant Growth Promoters ◽  
Genes Encoding ◽  
Resistance To Stress

ABSTRACT The genus Burkholderia includes strains pathogenic to animals and plants, bioremediators, or plant growth promoters. Genome sequence analyses of representative Burkholderia cepacia complex (Bcc) and non-Bcc strains for the presence of the bce-I gene cluster, directing the biosynthesis of the exopolysaccharide (EPS) cepacian, further extended this previously described cluster by another 9 genes. The genes in the bce-II cluster were named bceM to bceU and encode products putatively involved in nucleotide sugar precursor biosynthesis and repeat unit assembly, modification, and translocation across the cytoplasmic membrane. Disruption of the B. cepacia IST408 bceQ and bceR genes, encoding a putative repeat unit flippase and a glycosyltransferase, respectively, resulted in the abolishment of cepacian biosynthesis. A mutation in the bceS gene, encoding a putative acyltransferase, did not affect EPS production yield significantly but decreased its acetylation content by approximately 20%. Quantitative real-time reverse transcription-PCR experiments confirmed the induction of genes in the bce-I and bce-II clusters in a B urkholderia multivorans EPS producer clinical isolate in comparison to the level for its isogenic EPS-defective strain. Fourier Transform infrared spectroscopy analysis confirmed that the exopolysaccharide produced by 10 Burkholderia isolates tested was cepacian. The ability of Burkholderia strains to withstand desiccation and metal ion stress was higher when bacteria were incubated in the presence of 2.5 g/liter of cepacian, suggesting that this EPS plays a role in the survival of these bacteria by contributing to their ability to thrive in different environments.

scholarly journals An investigation of Burkholderia cepacia complex methylomes via SMRT sequencing and mutant analysis

2020 ◽  
Author(s):  
Olga Mannweiler ◽  
Marta Pinto-Carbó ◽  
Martina Lardi ◽  
Kirsty Agnoli ◽  
Leo Eberl
Keyword(s):  
Burkholderia Cepacia ◽  
Essential Gene ◽  
Epigenetic Modification ◽  
Burkholderia Cepacia Complex ◽  
Phenotypic Traits ◽  
Opportunistic Pathogens ◽  
Smrt Sequencing ◽  
Wide Range ◽  
Methylation Patterns ◽  
The Impact

AbstractThe Burkholderia cepacia complex (Bcc) is a group of 22 closely related opportunistic pathogens which produce a wide range of bioactive secondary metabolites with great biotechnological potential, for example in biocontrol and bioremediation.This study aimed to investigate methylation in the Bcc by SMRT sequencing, and to determine the impact of restriction-methylation (RM) systems on genome protection and stability and on phenotypic traits. We constructed and analysed a mutant lacking all RM components in the clinical isolate B. cenocepacia H111. We show that a previously identified essential gene of strain H111, gp51, encoding a methylase within a prophage region, is required for maintaining the bacteriophage in a lysogenic state. We speculate that epigenetic modification of a phage promoter provides a mechanism for a constant, low level of phage production within the bacterial population. We also found that, in addition to bacteriophage induction, methylation was important in biofilm formation, cell shape, motility, siderophore production and membrane vesicle production. Moreover, we found that DNA methylation had a massive effect on the maintenance of the smallest replicon present in this bacterium, which is essential for its virulence.In silico investigation revealed the presence of two core RM systems, present throughout the Bcc and beyond, suggesting that the acquisition of these RM systems occurred prior to the phylogenetic separation of the Bcc. We used SMRT sequencing of single mutants to experimentally assign the B. cenocepacia H111 methylases to their cognate motifs. Analysis of the distribution of methylation patterns suggested roles for m6A methylation in replication, since motifs recognised by the core Type III RM system were more abundant at the replication origins of the three H111 replicons, and in regions encoding functions related to cell motility and iron uptake.Author summaryWhile nucleotide sequence determines an organism’s proteins, methylation of the nucleotides themselves can confer additional properties. In bacteria, methyltransferases methylate specific motifs to allow discrimination of ‘self’ from ‘non-self’ DNA, e.g. from bacteriophages. Restriction enzymes detect ‘non-self’ methylation patterns and cut foreign DNA. Furthermore, methylation of promoter regions can influence gene expression and hence affect phenotype. In this study, we determined the methylated motifs of four strains from the Burkholderia cepacia complex of opportunistic pathogens. Three novel motifs were found, and two that were previously identified in a related species. We deleted the genes encoding the restriction and modification components in a representative strain from among the four sequenced. In this study, methylation is shown to affect various phenotypes, among which maintenance of the lysogenic state of a phage and segregational stability of the smallest megareplicon are most remarkable.

scholarly journals Role of the DmpR-Mediated Regulatory Circuit in Bacterial Biodegradation Properties in Methylphenol-Amended Soils

2001 ◽  
Vol 67 (1) ◽  
pp. 162-171 ◽  
Author(s):  
Inga Sarand ◽  
Eleonore Skärfstad ◽  
Mats Forsman ◽  
Martin Romantschuk ◽  
Victoria Shingler
Keyword(s):  
Regulatory Protein ◽  
Type System ◽  
Single Mutation ◽  
Wild Type ◽  
Regulatory Circuit ◽  
Wide Range ◽  
Genes Encoding ◽  
Effector Response

ABSTRACT Pathway substrates and some structural analogues directly activate the regulatory protein DmpR to promote transcription of thedmp operon genes encoding the (methyl)phenol degradative pathway of Pseudomonas sp. strain CF600. While a wide range of phenols can activate DmpR, the location and nature of substituents on the basic phenolic ring can limit the level of activation and thus utilization of some compounds as assessed by growth on plates. Here we address the role of the aromatic effector response of DmpR in determining degradative properties in two soil matrices that provide different nutritional conditions. Using the wild-type system and an isogenic counterpart containing a DmpR mutant with enhanced ability to respond to para-substituted phenols, we demonstrate (i) that the enhanced in vitro biodegradative capacity of the regulator mutant strain is manifested in the two different soil types and (ii) that exposure of the wild-type strain to 4-methylphenol-contaminated soil led to rapid selection of a subpopulation exhibiting enhanced capacities to degrade the compound. Genetic and functional analyses of 10 of these derivatives demonstrated that all harbored a single mutation in the sensory domain of DmpR that mediated the phenotype in each case. These findings establish a dominating role for the aromatic effector response of DmpR in determining degradation properties. Moreover, the results indicate that the ability to rapidly adapt regulator properties to different profiles of polluting compounds may underlie the evolutionary success of DmpR-like regulators in controlling aromatic catabolic pathways.

scholarly journals Characterization and identification of naturally transgenic species Linaria vulgaris pathogenic mycromycetes

2018 ◽  
Vol 16 (1) ◽  
pp. 27-34
Author(s):  
Sofia V. Sokornova ◽  
Elena L. Gasich ◽  
Victoria D. Bemova ◽  
Tatiana V. Matveeva
Keyword(s):  
Host Range ◽  
Large Subunit ◽  
Molecular Data ◽  
Microbial Interactions ◽  
Internal Transcribed Spacers ◽  
Broad Host Range ◽  
Narrow Host Range ◽  
Wide Range ◽  
Phoma Herbarum

In nature there are species containing homologs of T-DNA genes of agrobacteria (сT-DNA) in their genomes. Such plants are called naturally transgenic ones. Interaction with the microbiota is one of the possible functions of cT-DNA, discussed in the literature. Linaria plants are the most suitable for the investigation of the probable ecological role of T-DNA, since they widely spread. The first stage in the evaluation of plant-microbial interactions involving these plants is the description of isolates with contrasting virulence for toadflax. The search and DNA-barcoding of such isolates of Phoma-like fungi was the goal of this work. 14 strains isolated from the plants of the families Plantaginaceae and Scrophullariaceae were analyzed. The of multilocus analysis included amplification and sequencing of internal transcribed spacers, a large subunit of RNA, a tubulin gene. Based on molecular data, 9 strains were assigned to the species Boeremia exigua, which has a wide range of habitats and a wide specialization. Strains of this species were virulent against L. vulgaris, but differed in aggressiveness with respect to this plant. Thus, a collection of strains was characterized, which can later be used for a more detailed study of the immune response of the naturally-transgenic L. vulgaris plant in response to inoculation with the B. exigua phytopathogen. As a result of the work, we identified the narrow host range fungi Heterophoma novae-verbascicola, and broad host range pathogens Plectosphaerella cucumerina, Phoma herbarum and Trichothecium roseum. Among them, only P. cucumerina was a weak pathogen of L. vulgaris. These results confirm the early data on the depleted mycobiota of L. vulgaris.

scholarly journals The Role of Aflatoxins in Aspergillus flavus Resistance to Stress

2021 ◽  
Author(s):  
Massimo Reverberi ◽  
Marzia Beccaccioli ◽  
Marco Zaccaria
Keyword(s):  
Reactive Oxygen Species ◽  
Secondary Metabolites ◽  
Natural Population ◽  
Aspergillus Flavus ◽  
Opportunistic Pathogens ◽  
Aspergillus Section Flavi ◽  
Resistance To Stress ◽  
Niche Competition ◽  
Aspergillus Section

Aspergillus section Flavi produce the aflatoxins, secondary metabolites toxic to humans and animals. Why do these fungi produce aflatoxins? They do not have a clear role in pathogenicity or in niche competition. Aspergillus employs a considerable amount of energy to synthesize them: more than 20 enzymatic catalyzes are needed. Within the A. flavus species, all opportunistic pathogens of maize, more than half of the natural population are atoxigenic, indicating that aflatoxins are not so obviously linked to an enhancement of population fitness. The perspective changes in A. parasiticus, pathogen to peanuts, where more than 90% of the natural population produce the four aflatoxins. In this chapter, we aim to discuss our recent hypothesis that aflatoxins act as antioxidants providing more time to Aspergillus to “escape” an exploited substrate, that in the meanwhile is “fully charged” with reactive oxygen species and oxylipins.

Sign in / Sign up

Export Citation Format

Share Document