CHAPTER 23: Mechanisms of Pathogenicity and Emergence of New Plant-Pathogenic Species in the Genus Streptomyces

2016 ◽  
pp. 445-456
Keyword(s):  
Pathogenic Species ◽  
Genus Streptomyces

scholarly journals The Cellobiose Sensor CebR Is the Gatekeeper of Streptomyces scabies Pathogenicity

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Isolde M. Francis ◽  
Samuel Jourdan ◽  
Steven Fanara ◽  
Rosemary Loria ◽  
Sébastien Rigali
Keyword(s):  
Binding Sites ◽  
Molecular Mechanisms ◽  
Streptomyces Scabies ◽  
Cellulose Synthesis ◽  
Primary Metabolism ◽  
Unexpected Result ◽  
Pathogenic Species ◽  
Synthesis Inhibitor ◽  
Genus Streptomyces ◽  
Thaxtomin A

ABSTRACTA relatively small number of species in the large genus Streptomyces are pathogenic; the best characterized of these is Streptomyces scabies. The pathogenicity of S. scabies strains is dependent on the production of the nitrated diketopiperazine thaxtomin A, which is a potent plant cellulose synthesis inhibitor. Much is known about the genetic loci associated with plant virulence; however, the molecular mechanisms by which S. scabies triggers expression of thaxtomin biosynthetic genes, beyond the pathway-specific activator TxtR, are not well understood. In this study, we demonstrate that binding sites for the cellulose utilization repressor CebR occur and function within the thaxtomin biosynthetic cluster. This was an unexpected result, as CebR is devoted to primary metabolism and nutritive functions in nonpathogenic streptomycetes. In S. scabies, cellobiose and cellotriose inhibit the DNA-binding ability of CebR, leading to an increased expression of the thaxtomin biosynthetic and regulatory genestxtA,txtB, andtxtR. Deletion ofcebRresults in constitutive thaxtomin A production and hypervirulence of S. scabies. The pathogenicity of S. scabies is thus under dual direct positive and negative transcriptional control where CebR is the cellobiose-sensing key that locks the expression oftxtR, the key necessary to unlock the production of the phytotoxin. Interestingly, CebR-binding sites also lie upstream of and within the thaxtomin biosynthetic clusters in Streptomyces turgidiscabies and Streptomyces acidiscabies, suggesting that CebR is most likely an important regulator of virulence in these plant-pathogenic species as well.IMPORTANCEWhat makes a microorganism pathogenic is not limited to the genes acquired for virulence. Using the main causative agent of scab lesions on root and tuber crops as an example, our work identified the subtle but essential genetic changes that generate thecis-acting elements necessary for proper timing of the expression of the cluster of genes responsible for the biosynthesis of thaxtomin A, the primary virulence factor in plant-pathogenic streptomycetes. These data illustrate a situation in which a regulator associated with primary metabolism in nonpathogens, CebR, has been coopted as a master regulator of virulence in pathogenic species. Furthermore, the manipulation of CebR-mediated control of thaxtomin production will facilitate overproduction of this natural and biodegradable herbicide for commercial purposes. Our work thus provides a concrete example of how a strictly theoretical and computational work was able to elucidate a regulatory mechanism associated with the virulence of a plant pathogen and to generate solutions to purely agro-industrial concerns.

Complete genome of mangrove-derived anti-MRSA streptomycete, Streptomyces pluripotens MUSC 135T

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Kok-Gan Chan ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Bey-Hing Goh ◽  
...  
Keyword(s):  
Complete Genome ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Gene Clusters ◽  
Salmonella Typhi ◽  
Bacteriocin Production ◽  
Trna Genes ◽  
Genus Streptomyces ◽  
Mining Tool ◽  
Bioactive Potential ◽  
Effective Drugs

Microorganisms serve as attractive resources, owing to their ability to synthesize structurally-diverse substanceswith various bioactivities. Within the Bacteria domain, members of the genus Streptomyces have demonstrated remarkableability to produce clinically useful, secondary metabolites such as anticancer, antioxidants, antivirals and antibacterials.Streptomyces pluripotens MUSC 135T was isolated as novel strain from mangrove forest in Malaysia. This strain exhibitedbroad spectrum bacteriocin against several pathogens including methicillin-resistant Staphylococcus aureus (MRSA) strainATCC BAA-44, Salmonella typhi ATCC 19430T and Aeromonas hydrophila ATCC 7966T. Thus, the strain was selected forwhole genome sequencing as an attempt to explore its bioactive potential. Here we report the first complete genome of S.pluripotens MUSC 135T genome which comprise of 7.35 Mbp with G+C content of 69.9 %. A total of 6,404 open readingframes (ORFs) were predicted, along with 18 rRNA and 69 tRNA genes. Using bacteriocin mining tool, BAGEL detectedeights gene clusters associated with bacteriocin production including lanthipeptides and linear azol(in)e-containing peptides(LAPs). Members of Streptomyces have contributed greatly towards improving lives, particularly against deadly infectionsand chronic diseases. The availability of S. pluripotens MUSC 135T genome sequence has opened new window for drugdiscovery, particularly for effective drugs against harmful pathogens such as MRSA and certainly deserves further detailedstudy.

Conventional Versus Natural Alternative Treatments for Leishmaniasis: A Review

2018 ◽  
Vol 18 (15) ◽  
pp. 1275-1286 ◽  
Author(s):  
Luiz Felipe Domingues Passero ◽  
Lucas Antal Cruz ◽  
Gabriela Santos-Gomes ◽  
Eliana Rodrigues ◽  
Márcia Dalastra Laurenti ◽  
...  
Keyword(s):  
Side Effects ◽  
Visceral Leishmaniasis ◽  
Traditional Knowledge ◽  
Conventional Therapy ◽  
Pathogenic Species ◽  
Action Mechanism ◽  
In Vivo Assays ◽  
Clinical Forms

Leishmaniasis is a neglected disease caused by protozoan belonging to the Leishmania genus. There are at least 16 pathogenic species for humans that are able to cause different clinical forms, such as cutaneous or visceral leishmaniasis. In spite of the different species and clinical forms, the treatment is performed with few drug options that, in most cases, are considered outdated. In addition, patients under classical treatment show serious side effects during drug administration, moreover parasites are able to become resistant to medicines. Thus, it is believed and well accepted that is urgent and necessary to develop new therapeutic options to overpass these concerns about conventional therapy of leishmaniasis. The present review will focus on the efficacy, side effects and action mechanism of classic drugs used in the treatment of leishmaniasis, as well as the importance of traditional knowledge for directing a rational search toward the discovery and characterization of new and effective molecules (in vivo assays) from plants to be used against leishmaniasis.

scholarly journals Crystal Structure of Exotoxin A from Aeromonas Pathogenic Species

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 397 ◽  
Author(s):  
Geoffrey Masuyer
Keyword(s):  
Crystal Structure ◽  
Metal Binding ◽  
Elongation Factor ◽  
Pathogenic Species ◽  
Exotoxin A ◽  
Pseudomonas Exotoxin A ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Bacterial Virulence Factor ◽  
Interdomain Interactions

Aeromonas exotoxin A (AE) is a bacterial virulence factor recently discovered in a clinical case of necrotising fasciitis caused by the flesh-eating Aeromonas hydrophila. Here, database mining shows that AE is present in the genome of several emerging Aeromonas pathogenic species. The X-ray crystal structure of AE was solved at 2.3 Å and presents all the hallmarks common to diphthamide-specific mono-ADP-ribosylating toxins, suggesting AE is a fourth member of this family alongside the diphtheria toxin, Pseudomonas exotoxin A and cholix. Structural homology indicates AE may use a similar mechanism of cytotoxicity that targets eukaryotic elongation factor 2 and thus inhibition of protein synthesis. The structure of AE also highlights unique features including a metal binding site, and a negatively charged cleft that could play a role in interdomain interactions and may affect toxicity. This study raises new opportunities to engineer alternative toxin-based molecules with pharmaceutical potential.

scholarly journals Discovery of fungal surface NADases predominantly present in pathogenic species

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Øyvind Strømland ◽  
Juha P. Kallio ◽  
Annica Pschibul ◽  
Renate H. Skoge ◽  
Hulda M. Harðardóttir ◽  
...  
Keyword(s):  
Cell Death ◽  
Aspergillus Fumigatus ◽  
Neurospora Crassa ◽  
Binding Site ◽  
Host Cell ◽  
Nicotinamide Adenine Dinucleotide ◽  
Catalytic Mechanism ◽  
Pathogenic Species ◽  
X Ray ◽  
Cellular Bioenergetics

AbstractNicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.

TMKS8A, an antibacterial and cytotoxic chlorinated α-lapachone, from a sea slug-derived actinomycete of the genus Streptomyces

2021 ◽  
Author(s):  
Zhiwei Zhang ◽  
Mada Triandala Sibero ◽  
Akiho Kai ◽  
Keisuke Fukaya ◽  
Daisuke Urabe ◽  
...  
Keyword(s):  
Genus Streptomyces ◽  
Sea Slug

scholarly journals EspM Is a Conserved Transcription Factor That Regulates Gene Expression in Response to the ESX-1 System

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin G. Sanchez ◽  
Micah J. Ferrell ◽  
Alexandra E. Chirakos ◽  
Kathleen R. Nicholson ◽  
Robert B. Abramovitch ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Protein Transport ◽  
Transcriptional Response ◽  
Secretion System ◽  
Pathogenic Species ◽  
Macrophage Infection ◽  
Content Type ◽  
Link Type ◽  
Phagosomal Membrane

ABSTRACT Pathogenic mycobacteria encounter multiple environments during macrophage infection. Temporally, the bacteria are engulfed into the phagosome, lyse the phagosomal membrane, and interact with the cytosol before spreading to another cell. Virulence factors secreted by the mycobacterial ESX-1 (ESAT-6-system-1) secretion system mediate the essential transition from the phagosome to the cytosol. It was recently discovered that the ESX-1 system also regulates mycobacterial gene expression in Mycobacterium marinum (R. E. Bosserman, T. T. Nguyen, K. G. Sanchez, A. E. Chirakos, et al., Proc Natl Acad Sci U S A 114:E10772–E10781, 2017, https://doi.org/10.1073/pnas.1710167114), a nontuberculous mycobacterial pathogen, and in the human-pathogenic species M. tuberculosis (A. M. Abdallah, E. M. Weerdenburg, Q. Guan, R. Ummels, et al., PLoS One 14:e0211003, 2019, https://doi.org/10.1371/journal.pone.0211003). It is not known how the ESX-1 system regulates gene expression. Here, we identify the first transcription factor required for the ESX-1-dependent transcriptional response in pathogenic mycobacteria. We demonstrate that the gene divergently transcribed from the whiB6 gene and adjacent to the ESX-1 locus in mycobacterial pathogens encodes a conserved transcription factor (MMAR_5438, Rv3863, now espM). We prove that EspM from both M. marinum and M. tuberculosis directly and specifically binds the whiB6-espM intergenic region. We show that EspM is required for ESX-1-dependent repression of whiB6 expression and for the regulation of ESX-1-associated gene expression. Finally, we demonstrate that EspM functions to fine-tune ESX-1 activity in M. marinum. Taking the data together, this report extends the esx-1 locus, defines a conserved regulator of the ESX-1 virulence pathway, and begins to elucidate how the ESX-1 system regulates gene expression. IMPORTANCE Mycobacterial pathogens use the ESX-1 system to transport protein substrates that mediate essential interactions with the host during infection. We previously demonstrated that in addition to transporting proteins, the ESX-1 secretion system regulates gene expression. Here, we identify a conserved transcription factor that regulates gene expression in response to the ESX-1 system. We demonstrate that this transcription factor is functionally conserved in M. marinum, a pathogen of ectothermic animals; M. tuberculosis, the human-pathogenic species that causes tuberculosis; and M. smegmatis, a nonpathogenic mycobacterial species. These findings provide the first mechanistic insight into how the ESX-1 system elicits a transcriptional response, a function of this protein transport system that was previously unknown.

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