Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• aboveground plant–insect, plant–pathogen and plant–plant interactions [11]. However, terpenes might also play important roles in belowground interspecific interactions [12]. Terpene synthases are in fact widely distributed among soil microorganisms, and they have been mainly studied in Streptomyces species [9

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the ability of the Leishmania pathogen to evade and abate immune responses. In an effort to develop anti-leishmaniasis vaccines and adjuvants, novel carbohydrate-based probes were made to

• study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was

• designed, with a tethered fluorophore. Further attachment of the glycodendrimer to a biocompatible, surface eroding microparticle allows for targeted uptake and internalization of the pathogen-associated oligosaccharide by phagocytic immune cells. The α-1,2-trimannose-linked bioerodible microparticles were

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized

• unsaturation and can be O- or N-methylated [1][2][3]. In the opportunistic pathogen Pseudomonas aeruginosa, AQ derivatives with heptyl or nonyl side chains are prevalent [3][7][8][9]. 2-Heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal, PQS) and its biosynthetic precursor 2-heptyl-4(1H)-quinolone

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• target cells of Mtb bacteria are primarily alveolar macrophages, which internalize the pathogen through phagocytosis [6]. These innate immune cells initiate a number of responses to limit bacterial replication and spread with the ultimate goal of eradicating the pathogen. However, Mtb has evolved

• indeed shown that alveolar type II pneumocytes can also become infected with Mtb bacteria in vitro and in vivo [13][14][15][16][17]. Furthermore, dendritic cells and neutrophils internalize Mtb bacteria and are important key players in the immune response against this pathogen [18][19][20]. Bacterial

• , both mycobacteria and mammalian host cells possess unique subsets of surface-exposed carbohydrates, which could function as ligands for putative host- or self-lectins, in processes such as interbacterial aggregation or host–pathogen interactions. Bacterial lectins The existence of bacterially-expressed

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen Pseudomonas aeruginosa. Cisplatin was found to effectively kill strains of P. aeruginosa. In such

• infections. Keywords: biofilm; cisplatin; Pseudomonas aeruginosa; resistance; type III secretion; Introduction Pseudomonas aeruginosa is a leading nosocomial pathogen which causes, among others, corneal, chronic otitis media, urinary tract (UTI) and respiratory tract infections [1]. P. aeruginosa is also

• the main cause of fatal infections in patients with cystic fibrosis (CF) [2] and cancer patients [3][4]. The success of P. aeruginosa as a leading pathogen is attributed to its ability to form resilient biofilms, resist antimicrobials and secrete virulence products. Microbial cells resident in

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• volatiles seem to be involved in the plant pathogenicity of fungi, as recently observed for 3,4-dimethylpentan-4-olide (4), a volatile from the ash pathogen Hymenoscyphus fraxineus that currently threatens the European ash population [10]. Both enantiomers of this lactone were found to inhibit ash seed

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• , respectively). A subsequent antibacterial screening showed that the lead pyrimidine 40 was also a moderate inhibitor of the growth of the Gram-positive pathogen B. subtilis and the Gram-negative microorganism E. coli. The same research group developed further SAR studies using compound 41 (Figure 9) as lead of

• are other strategies that are being explored towards the discovery of new antibiotics with novel mechanisms of action such as for example inhibitors of host–pathogen interactions and of the type 3 secretion system (T3SS) in Gram-negative bacteria, nonetheless, the specific targets remain unknown or

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• hypothesized that by “disarming” the pathogen, rather than inhibiting its growth, selective pressure for resistance development will be much lower. Furthermore, reduction of bacterial virulence directly protects the host, and at the same time renders the bacteria more susceptible towards the host defense

• system and antibiotics. The Centers for Disease Control and Prevention (CDC) have listed a number of bacteria that present serious, urgent and concerning threats [8]. One of these problematic bacteria is methicillin-resistant Staphylococcus aureus (MRSA), a human pathogen that causes a wide range of

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• analogues was observed to inhibit production of the virulence factor pyocyanin in the human pathogen Pseudomonas aeruginosa, which may be a result of their similarity to the Pseudomonas quinolone signal (PQS) quorum sensing autoinducer. This provided new insights regarding the effect of N-substitution in

• -position, there is a structural resemblance to the Pseudomonas quinolone signal (PQS), and its biosynthetic precursor 2-heptyl-4(1H)-quinolone (HHQ), which are vital to the cooperative behaviour of the human pathogen Pseudomonas aeruginosa via quorum sensing (QS). This is a means by which bacteria alter

• in quorum sensing signalling by the human pathogen Pseudomonas aeruginosa, and 2-heptyl-4(1H)-quinolone (HHQ), the biosynthetic precursor of PQS. Growth of E. coli ESS with time in the presence of 200 μM of each compound. A) Natural product series. B) Saturated analogue series. C) Truncated analogue

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• LuxI-type synthases and do not produce AHLs; thus, SdiA represents an orphan [14] or “solo” LuxR-type receptor, a class that is rapidly growing in number [15]. SdiA from the common foodborne pathogen, S. enterica serovar Typhimurium (S. Typhimurium hereafter), has been a target of research [16][17][18

• of a LuxI-type synthase (via a plasmid) into S. Typhimurium provided the pathogen with a competitive advantage in colonizing mice over bacteria that lacked the plasmid [18]. Similarly, enterohemorrhagic E. coli (EHEC) requires SdiA and AHLs produced by other species in the bovine rumen in order to

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , 66123 Saarbrücken, Germany German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Saarbrücken, Germany 10.3762/bjoc.14.241 Abstract The Gram-negative opportunistic pathogen Pseudomonas aeruginosa causes severe nosocomial infections. It uses quorum sensing (QS) to regulate and

• bactericidal or bacteriostatic effects, but mediate their effect through pathogen-specific action on virulence mechanisms, has been unveiled. This short review focuses on the current knowledge of one particular antivirulence strategy against the important pathogen Pseudomonas aeruginosa, which is based on the

• well as cell envelope properties or biofilm formation [15]. All the mechanisms described above help to explain the notion that established chronic P. aeruginosa infections are notoriously difficult to eradicate. This ubiquitous opportunistic pathogen is able to cause infections basically in every niche

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• pressure can lead to the overgrowth of the initial infective population with a resistant variant of the pathogen, rendering the antibiotic substance ineffective. Especially prevalent in the hospital setting, the abundance of resistance prevents efficient treatment of infected patients. The so-called ESKAPE

• pioneering review by Clatworthy et al. in 2007, entitled ‘Targeting virulence: a new paradigm for antimicrobial therapy’ [8], which has been cited approximately 800 times. In sharp contrast to traditional antibiotics that kill or impair bacterial viability, this new approach aims to disarm the pathogen

• . Interfering with the interaction of the pathogen with its host in this way is believed to both reduce damage to the host and to enable the host to clear the microbe from its system. Furthermore, as antivirulence drugs do not kill, it is believed that the selection pressure for resistant mutants will be

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• develop anti-QS therapeutic strategies to fight against P. aeruginosa infections. Keywords: adhesion; host–pathogen interaction; inflammation; Pseudomonas; quorum sensing; Introduction Pseudomonas (P.) aeruginosa is an opportunistic pathogen that causes severe and persistent infections in immune

• . Pseudomonas aeruginosa is recognized as the principal pathogen responsible of high morbidity and mortality in patients with cystic fibrosis, one of the most common life-threatening autosomal recessive genetic disease in Northwest European populations, determined by mutations in the cystic fibrosis

• . aeruginosa QSSMs on key bacterial virulence factors such as attachment and biofilm formation was shown, as these behaviors are very important for the progression of the infectious process and represent the main host-pathogen interactions. Bacterial adherence to inert substrata and biofilms developed at

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• significant attention as a potential antivirulence alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious human pathogen responsible for a variety of acute and chronic infections, utilizes the competence regulon and its associated signaling peptide, the competence stimulating peptide

• pathogen that is responsible for a variety of acute and chronic infections, including pneumonia, bacteremia, sepsis, meningitis and otitis media, resulting in >22,000 deaths and direct medical costs totaling $3.5 billion a year in the United States alone [20][21]. The QS circuitry of S. pneumoniae, known

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• -soluble fractions. Antimicrobial testings against Rhizopus oryzae (the fungal pathogen of rice seedling blight), Trichophyton rubrum (dermatophytosis pathogen), and Tenacibaculum maritimum (the causative organism for skin ulcers in marine fish) revealed that the second fraction was the most active. The

• sativus), grown in an experimental farm at Mie University (Kurimamachiya-cho, Tsu, Mie) in 2010. The bacterial collection was cultured in 4 different media to give 152 extracts, which were screened against Edwardsiella ictaluri NBRC105724T (pathogen of enteric septicemia of freshwater fish), T. maritimum

• NBRC16015, Trichophyton rubrum NBRC5467, Candida albicans NBRC0197 (human opportunistic pathogen), R. oryzae NBRC4705, Glomerella cingulata NBRC5907 (pathogen of anthracnose), Ralstonia solanacearum SUPP1541 (pathogen of bacterial wilt of Solanaceous plants), Rhizobium radiobacter NBRC14554 (pathogen of

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• roqueforti [7][8][9], trichodiene (4) is the parent hydrocarbon of the trichothecene family of mycotoxins in various Trichothecium and Fusarium strains [10], and the diterpene ent-kaurene (5) is the precursor of gibberellins, a class of plant hormones that are produced in large amounts by the rice pathogen

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• . The receptors of the innate immune system can detect particular components present in bacteria, viruses or fungi which are designated as “pathogen associated molecular patterns” (PAMPs) [1]. These receptors, termed pattern recognition receptors (PRRs), are able of sensing and responding to PAMPs. The

• inflammation. 2. Synthesis of lipid A containing unusual lipid chains or lacking 1-phosphate group 2.1. Synthesis of variably acylated Porphyromonas gingivalis lipid A Porphyromonas gingivalis is a major bacterial pathogen strongly implicated in periodontal disease (periodontitis) that is the primary cause of

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• antibiotics. The fact that these cyclodextrin derivatives might be loaded with an antibiotic allows speculating that a possible antibiotic–CD complex could target the pathogen and in the meanwhile to bind and sequester extracellular DNA, inhibiting its role in vivo. Finally, a particular mention is deserved

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• ion [1][2][3][4]. CLECs are involved in a wide range of biological processes, such as pathogen recognition and intercellular adhesion [5][6][7]. A large number of CLEC structures, including animal, plant and bacterial lectins, are available in the Protein Data Bank [8]. A second large family of

• mechanisms, for instance by pathogen internalization as in the case of BDCA-2 and langerin, by pathogen opsonization as mediated by SP-D and MBP, or by T-cell interactions as mediated by DC-SIGN and DC-SIGNR [25][26]. In contrast, pathogens have developed numerous adhesins that mediate their interaction with

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• ; Review Introduction Carbohydrates are widely present in nature and many of them are involved in important physiological and pathological events, such as anticoagulation, inflammation and pathogen infection [1][2]. In order to explore their biological functions, oligosaccharides with high purity are

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• Matthias Gehringer Karl-Heinz Altmann Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, Vladimir-Prelog-Weg 4, 8093 Zürich, Switzerland 10.3762/bjoc.13.159 Abstract Mycolactones are a group of macrolides excreted by the human pathogen Mycobacterium

• ulcer Buruli ulcer is a chronic and debilitating disease characterized by skin ulcers and necrotic cutaneous lesions. Ulcers typically occur at the limbs and can extend to 15% of the skin surface if untreated. The disease is caused by the pathogen Mycobacterium ulcerans and represents the third most

• Republic of the Congo), the pathogen is also endemic in South America, the Western Pacific region (incl. Australia) and Asia (e.g., China and Japan). In certain highly endemic regions like the Zou department in southern Benin, the prevalence of Buruli ulcer can even exceed that of tuberculosis or leprosy

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• unknown mechanism for osteogenesis that may be exploited to stimulate bone growth in grafts or in patients suffering age-related bone loss. Machine learning and evolutionary design: pathogen-resistant polymers Antimicrobial drugs and materials are becoming extremely important due to the rise in nosocomial

• identify low adhesion materials for coating medical devices [45]. These data were used to generate a sparse machine learning model for each pathogen (Figure 13) that predicted pathogen attachment and described the relationship between polymer surface chemistry and attachment [46]. The pathogen attachment

• performance of the polymers determined experimentally and predicted by the machine learning models was used as a fitness function to evolve several populations of polymers with deceasing pathogen affinities. Subsequently, machine learning methods were used to generate a multipathogen model that could

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• data acquisition systems [81]. An illustration of how BioSAXS experiments can help to complete data obtained by protein crystallography is given by the characterization of the full structural assembly of the lectin of Burkholderia cenocepacia, an opportunistic bacterial pathogen. Throughout biochemical

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• glycoprobe interact with a microplate displaying AFP-L3, LcA strongly bind to AFP-L3 releasing from the supramolecular glycoprobe GAuNPs in a concentration which can be measured via UV–vis spectroscopy. Chiodo et al. [84] gave their contribution in the development of early stage cancer or pathogen diagnosis

• Galf, a five-membered form of galactose found in nonmammalian pathogenic species, i.e., the fungus Aspergillus, is able to modulate the innate immune response via dendritic cells, suggesting Galf-GNPs as versatile tools in functional studies to address the role of Galf in host-pathogen interaction. DC

• -based approach, which aim to trigger the production of specific and functional antibodies that prevent initial infection limiting pathogen/viral dissemination. Recent publications suggest that many different aspects are becoming clear and have to be underlined. The design of anti HIV-1 vaccines depends

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• biological activities. Various microbes, reported in the literature, can accomplish the synthesis of pyrazinone derivatives [3][4][5][6]. For instance, phevalin (1) and tyrvalin (2), pyrazinone derivatives synthesized by a serious human pathogen, Staphylococcus aureus, act as protein kinase inhibitors