Permeability enhancers sensitize β-lactamase-expressing Enterobacteriaceae and Pseudomonas aeruginosa to β-lactamase inhibitors thereby restoring their β-lactam susceptibility.

Int J Antimicrob Agents. 2020 Apr 23;:105986

Authors: Ferrer-Espada R, Sánchez-Gómez S, Pitts B, Stewart PS, Martínez-de-Tejada G

Abstract
β-lactamases are the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria. Although there are β-lactamase inhibitors (BLIs) available, β-lactam-BLI combinations are increasingly being neutralized by diverse mechanisms of bacterial resistance. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of BLIs necessary to sensitize bacteria to antibiotics that are β-lactamase substrates. To test this hypothesis, we performed checkerboard assays and measured the ability of several AMPs, to synergize with piperacillin, ticarcillin, amoxicillin, ampicillin and ceftazidime in the presence of either, tazobactam, clavulanic acid, sulbactam, aztreonam, phenylboronic acid (PBA) or oxacillin. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae overexpressing β-lactamases. Synergy between polymyxin B nonapeptide (PMBN) and tazobactam boosted piperacillin activity by a factor of 128 in E. coli (from 256 to 2 mg/L, fractional inhibitory concentration index (FICI)≤0.02) and by a factor of at least 64 in K. pneumoniae (from 1024 mg/L to 16 mg/L, FICI≤0.05). Synergy between PMBN and PBA enhanced ceftazidime activity 133 times in P. aeruginosa (from 16 mg/L to 0.12 mg/L, FICI≤0.03). As a consequence, MICs of all the antibiotics tested were brought down to therapeutic range. In addition, the combinations also reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. Ceftazidime/PBA/PMBN at 50 times the planktonic MIC caused a 10 million-fold reduction in the viability of mature biofilms. We proved that AMPs can synergize with BLIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics.

PMID: 32335279 [PubMed - as supplied by publisher]

Preface: Life through death-Key role of cellular suicide for colonial and organismal homeostasis.

Int Rev Cell Mol Biol. 2020;352:xi-xv

Authors: Spetz J, Galluzzi L

PMID: 32334819 [PubMed - as supplied by publisher]

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Crop genetics research in Asia: improving food security and nutrition.

Theor Appl Genet. 2020 Apr 18;:

Authors: Zhang Q, Xu M, Xia X, Komatsuda T, Varshney RK, Shi K

PMID: 32306095 [PubMed - as supplied by publisher]

Exploiting the natural variation in tomato to define pathway structure and metabolic regulation of fruit polyphenolics in the lycopersicum complex.

Mol Plant. 2020 Apr 16;:

Authors: Tohge T, Scossa F, Wendenburg R, Frasse P, Balbo I, Watanabe M, Alseekh S, Jadhav SS, Delfin JC, Lohse M, Giavalisco P, Usadel B, Zhang Y, Luo J, Bouzayen M, Fernie AR

Abstract
Whilst the structures of plant primary metabolic pathways are generally well defined and highly conserved across species, those defining specialized metabolism are less well characterized and more highly variable across species. Here, we investigate polyphenolic metabolism in the lycopersicum complex by characterizing the underlying biosynthetic and decorative reactions which comprise the metabolic network of polyphenols across eight different species of tomato. For this purpose, GC- and LC-MS based metabolomics were carried out, in concert with the evaluation of cross-hybridized-microarray for MapMan based-transcriptomic analysis, and publically available RNA sequencing data for annotation of biosynthetic genes respectively, in different tissues of Solanum lycopersicum and wild tomato species. The combined data was used to compile species-specific metabolic networks of polyphenolic metabolism allowing the proposal of an entire pan-species biosynthetic framework as well as to annotate functions of decoration enzymes involved in the creation of metabolic diversity of the flavonoid pathway. The combined results are discussed both in the context of current understanding of tomato flavonol biosynthesis as well as a global view of metabolic shift during fruit ripening. Our results are providing an example as to how large-scale biology approaches can be used for the definition and refinement of large pathways of specialized metabolism.

PMID: 32305499 [PubMed - as supplied by publisher]

Tapping into the maize root microbiome to identify bacteria that promote growth under chilling conditions.

Microbiome. 2020 Apr 18;8(1):54

Authors: Beirinckx S, Viaene T, Haegeman A, Debode J, Amery F, Vandenabeele S, Nelissen H, Inzé D, Tito R, Raes J, De Tender C, Goormachtig S

Abstract
BACKGROUND: When maize (Zea mays L.) is grown in the Northern hemisphere, its development is heavily arrested by chilling temperatures, especially at the juvenile phase. As some endophytes are beneficial for plants under stress conditions, we analyzed the impact of chilling temperatures on the root microbiome and examined whether microbiome-based analysis might help to identify bacterial strains that could promote growth under these temperatures.
RESULTS: We investigated how the maize root microbiome composition changed by means of 16S rRNA gene amplicon sequencing when maize was grown at chilling temperatures in comparison to ambient temperatures by repeatedly cultivating maize in field soil. We identified 12 abundant and enriched bacterial families that colonize maize roots, consisting of bacteria recruited from the soil, whereas seed-derived endophytes were lowly represented. Chilling temperatures modified the root microbiome composition only slightly, but significantly. An enrichment of several chilling-responsive families was detected, of which the Comamonadaceae and the Pseudomonadaceae were the most abundant in the root endosphere of maize grown under chilling conditions, whereas only three were strongly depleted, among which the Streptomycetaceae. Additionally, a collection of bacterial strains isolated from maize roots was established and a selection was screened for growth-promoting effects on juvenile maize grown under chilling temperatures. Two promising strains that promoted maize growth under chilling conditions were identified that belonged to the root endophytic bacterial families, from which the relative abundance remained unchanged by variations in the growth temperature.
CONCLUSIONS: Our analyses indicate that chilling temperatures affect the bacterial community composition within the maize root endosphere. We further identified two bacterial strains that boost maize growth under chilling conditions. Their identity revealed that analyzing the chilling-responsive families did not help for their identification. As both strains belong to root endosphere enriched families, visualizing and comparing the bacterial diversity in these communities might still help to identify new PGPR strains. Additionally, a strain does not necessarely need to belong to a high abundant family in the root endosphere to provoke a growth-promoting effect in chilling conditions. Video abstract.

PMID: 32305066 [PubMed - as supplied by publisher]

Modes of allosteric regulation of the ubiquitination machinery.

Curr Opin Struct Biol. 2020 Apr 15;62:189-196

Authors: Rennie ML, Chaugule VK, Walden H

Abstract
Ubiquitination is a post-translational modification crucial for cellular signaling. A diverse range of enzymes constitute the machinery that mediates attachment of ubiquitin onto target proteins. This diversity allows the targeting of various proteins in a highly regulated fashion. Many of the enzymes have multiple domains or subunits that bind allosteric effectors and exhibit large conformational rearrangements to facilitate regulation. Here we consider recent examples of ubiquitin itself as an allosteric effector of RING and RBR E3 ligases, as well as advances in the understanding of allosteric regulatory elements within HECT E3 ligases.

PMID: 32305021 [PubMed - as supplied by publisher]

Towards understanding the hierarchical nitrogen signalling network in plants.

Curr Opin Plant Biol. 2020 Apr 15;55:60-65

Authors: Zhang Z, Hu B, Chu C

Abstract
Nitrogen (N) is the most abundant mineral elements in plants, and the application of inorganic N fertilizer makes huge contribution to the crop production and global food security. However, low N use efficiency (NUE) and overapplication of N fertilizers causes ever-growing environmental problems. Understanding the molecular mechanisms of N sensing and signalling in plants will provide molecular basis for NUE improvement of crops. Forward genetics screening and functional analysis have characterized the NRT1.1-NLP centered N signalling pathway at the cellular level. With the incorporation of systems biology approaches, a preliminary N regulatory network has been delineated. Meanwhile, long-distance N signalling has also been unveiled at the whole plant level. This review highlights most recent understanding of the N signalling network in plants, and also discusses how to further integrate hierarchical regulation of N signalling in plants.

PMID: 32304938 [PubMed - as supplied by publisher]

Temporal changes in microbial communities attached to forages with different lignocellulosic compositions in the cattle rumen.

FEMS Microbiol Ecol. 2020 Apr 18;:

Authors: Gharechahi J, Vahidi MF, Ding XZ, Han JL, Salekdeh GH

Abstract
The attachment of rumen microbes to feed particles is critical to feed fermentation, degradation and digestion. However, the extent to which the physicochemical properties of feeds influence the colonization by rumen microbes is still unclear. We hypothesized that rumen microbial communities may have differential preferences for attachments to feeds with varying lignocellulose properties. To this end, the structure and composition of microbial communities attached to six common forages with different lignocellulosic compositions were analyzed following in situ rumen incubation in male Taleshi cattle. The results showed that differences in lignocellulosic compositions significantly affected the inter-sample diversity of forage-attached microbial communities in the first 24 hours (h) of rumen incubation, during which the highest dry matter degradation was achieved. However, extension of the incubation to 96 h resulted in the development of more uniform microbial communities across the forages. Fibrobacteres were significantly overrepresented in the bacterial communities attached to the forages with the highest neutral detergent fiber contents. Ruminococcus tended to attach to the forages with low acid detergent lignin contents. The extent of dry matter fermentation was significantly correlated with the populations of Fibrobacteraceae, unclassified Bacteroidales, Ruminococcaceae and Spirochaetacea. Our findings suggested that lignocellulosic compositions, more specifically the cellulose components, significantly affected the microbial attachment to and thus the final digestion of the forages.

PMID: 32304321 [PubMed - as supplied by publisher]

Distinct lung microbial community states in patients with pulmonary tuberculosis.

Sci China Life Sci. 2020 Apr 14;:

Authors: Hu Y, Kang Y, Liu X, Cheng M, Dong J, Sun L, Zhu Y, Ren X, Yang Q, Chen X, Jin Q, Yang F

Abstract
An improved understanding of the lung microbiome may lead to better strategies to diagnose, treat, and prevent pulmonary tuberculosis (PTB). However, the characteristics of the lung microbiomes of patients with TB remain largely undefined. In this study, 163 bronchoalveolar lavage (BAL) samples were collected from 163 sputum-negative suspected PTB patients. Furthermore, 12 paired BAL samples were obtained from 12 Mycobacterium tuberculosis-positive (MTB+) patients before and after negative conversion following a two-month anti-TB treatment. The V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to characterize the microbial composition of the lungs. The results showed that the prevalence of MTB in the BAL samples was 42.9% (70/163) among the sputum-negative patients. The α-diversity of lung microbiota was significantly less diverse in MTB+ patients compared with Mycobacterium tuberculosis-negative (MTB-) patients. There was a significant difference in β-diversity between MTB+ and MTB- patients. MTB+ patients were enriched with Anoxybacillus, while MTB- patients were enriched with Prevotella, Alloprevotella, Veillonella, and Gemella. There was no significant difference between the Anoxybacillus detection rates of MTB+ and MTB- patients. The paired comparison between the BAL samples from MTB+ patients and their negative conversion showed that BAL negative-conversion microbiota had a higher α-diversity. In conclusion, distinct features of airway microbiota could be identified between samples from patients with and without MTB. Our results imply links between lung microbiota and different clinical groups of active PTB.

PMID: 32303963 [PubMed - as supplied by publisher]

Revisiting high-resolution crystal structure of Phormidium rubidum phycocyanin.

Photosynth Res. 2020 Apr 17;:

Authors: Sonani RR, Roszak AW, Liu H, Gross ML, Blankenship RE, Madamwar D, Cogdell RJ

Abstract
The crystal structure of phycocyanin (pr-PC) isolated from Phormidium rubidum A09DM (P. rubidum) is described at a resolution of 1.17 Å. Electron density maps derived from crystallographic data showed many clear differences in amino acid sequences when compared with the previously obtained gene-derived sequences. The differences were found in 57 positions (30 in α-subunit and 27 in β-subunit of pr-PC), in which all residues except one (β145Arg) are not interacting with the three phycocyanobilin chromophores. Highly purified pr-PC was then sequenced by mass spectrometry (MS) using LC-MS/MS. The MS data were analyzed using two independent proteomic search engines. As a result of this analysis, complete agreement between the polypeptide sequences and the electron density maps was obtained. We attribute the difference to multiple genes in the bacterium encoding the phycocyanin apoproteins and that the gene sequencing sequenced the wrong ones. We are not implying that protein sequencing by mass spectrometry is more accurate than that of gene sequencing. The final 1.17 Å structure of pr-PC allows the chromophore interactions with the protein to be described with high accuracy.

PMID: 32303893 [PubMed - as supplied by publisher]

Author Correction: Proteomic and interactomic insights into the molecular basis of cell functional diversity.

Nat Rev Mol Cell Biol. 2020 Apr 17;:

Authors: Bludau I, Aebersold R

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 32303723 [PubMed - as supplied by publisher]

A Seed-Specific Regulator of Triterpene Saponin Biosynthesis in Medicago truncatula.

Plant Cell. 2020 Apr 17;:

Authors: Ribeiro B, Lacchini E, Bicalho K, Mertens J, Arendt P, Vanden Bossche R, Calegario G, Gryffroy L, Ceulemans E, Buitink J, Goossens A, Pollier J

Abstract
Plants produce a vast array of defense compounds to protect themselves from pathogen attack or herbivore predation. A specific class of defense compounds are the saponins, bioactive glycosides with a steroidal or triterpenoid aglycone backbone. The model legume Medicago truncatula synthesizes two types of saponins, hemolytic saponins and non-hemolytic soyasaponins, which accumulate as specific blends in the different organs of the plant. Here we report the identification of a seed-specific transcription factor, TRITERPENE SAPONIN ACTIVATION REGULATOR 3 (TSAR3), which controls the hemolytic saponin biosynthesis in developing M. truncatula seeds. Co-expression analyses with TSAR3 in transcriptome datasets from developing M. truncatula seeds led to the identification of CYP88A13, a cytochrome P450 that catalyzes the C-16α hydroxylation of medicagenic acid towards zanhic acid, the final, yet unknown, oxidation step of the hemolytic saponin biosynthesis branch in M. truncatula. In addition, two uridine diphosphate glycosyltransferases, UGT73F18 and UGT73F19, which glucosylate hemolytic sapogenins at the C-3 position, were identified. The identified biosynthesis enzymes are organized in clusters of duplicated genes on the M. truncatula genome. This appears to be a quite common theme among saponin biosynthesis genes, especially glycosyltransferases, and may be the driving force of saponin metabolic evolution.

PMID: 32303662 [PubMed - as supplied by publisher]