A unified design allows fine-tuning of biosensor parameters and application across bacterial species

In comparison to existing structural, biochemical, and therapeutical data, the crystal structures of large ribosomal subunit from the eubacterial pathogen model Deinococcus radiodurans in complex with the 14-membered macrolides erythromycylamine, RU69874, and the 16-membered macrolide josamycin, highlighted the similarities and differences in macrolides binding to the ribosomal tunnel. The three compounds occupy the macrolide binding pocket with their desosamine or mycaminose aminosugar, the C4-C7 edge of the macrolactone ring and the cladinose sugar sharing similar positions and orientations, although the latter, known to be unnecessary for antibiotic activity, displays fewer contacts. The macrolactone ring displays altogether few contacts with the ribosome and can, therefore, tilt in order to optimize its interaction with the 23S rRNA. In addition to their contacts with nucleotides of domain V of the 23S RNA, erythromycylamine and RU69874 interact with domain II nucleotide U790, and RU69874 also reaches van der Waals distance from A752, in a fashion similar to that observed for the ketolides telithromycin and cethromycin. The variability in the sequences and consequently the diversity of the conformations of macrolide binding pockets in various bacterial species can explain the drug's altered level of effectiveness on different organisms and is thus an important factor in structure-based drug design.

Download Full-text

Novel σ B regulation modules of Gram-positive bacteria involve the use of complex hybrid histidine kinases

Microbiology ◽

10.1099/mic.0.045740-0 ◽

2011 ◽

Vol 157 (1) ◽

pp. 3-12 ◽

Cited By ~ 24

Author(s):

Mark de Been ◽

Christof Francke ◽

Roland J. Siezen ◽

Tjakko Abee

Keyword(s):

Sigma Factor ◽

Current Knowledge ◽

Bacterial Species ◽

Fine Tuning ◽

Activation Mechanism ◽

Future Research ◽

Control Mechanisms ◽

Gram Positive ◽

Gram Positive Bacteria ◽

Genome Context

A common bacterial strategy to cope with stressful conditions is the activation of alternative sigma factors that control specific regulons enabling targeted responses. In the human pathogen Bacillus cereus, activation of the major stress-responsive sigma factor σ B is controlled by a signalling route that involves the multi-sensor hybrid histidine kinase RsbK. RsbK-type kinases are not restricted to the B. cereus group, but occur in a wide variety of other bacterial species, including members of the the low-GC Gram-positive genera Geobacillus and Paenibacillus as well as the high-GC actinobacteria. Genome context and protein sequence analyses of 118 RsbK homologues revealed extreme variability in N-terminal sensory as well as C-terminal regulatory domains and suggested that RsbK-type kinases are subject to complex fine-tuning systems, including sensitization and desensitization via methylation and demethylation within the helical domain preceding the H-box. The RsbK-mediated stress-responsive sigma factor activation mechanism that has evolved in B. cereus and the other species differs markedly from the extensively studied and highly conserved RsbRST-mediated σ B activation route found in Bacillus subtilis and other low-GC Gram-positive bacteria. Implications for future research on sigma factor control mechanisms are presented and current knowledge gaps are briefly discussed.

Download Full-text

Gut microbiome recovery after antibiotic usage is mediated by specific bacterial species

10.1101/350470 ◽

2018 ◽

Cited By ~ 4

Author(s):

Tannistha Nandi ◽

Ivor Russel Lee ◽

Tarini Ghosh ◽

Amanda Hui Qi Ng ◽

Kern Rei Chng ◽

...

Keyword(s):

Gut Microbiome ◽

Synergistic Effects ◽

Bacterial Species ◽

Early Time ◽

Antibiotic Usage ◽

Fine Tuning ◽

Gut Health ◽

Bifidobacterium Adolescentis ◽

Carbohydrate Degradation ◽

Pathogen Colonization

AbstractDysbiosis in the gut microbiome due to antibiotic usage can persist for extended periods of time, impacting host health and increasing the risk for pathogen colonization. The specific factors associated with variability in gut microbiome recovery remain unknown. Using data from 4 different cohorts in 3 continents comprising >500 microbiome profiles from 117 subjects, we identified 20 bacterial species exhibiting robust association with gut microbiome recovery post antibiotic therapy. Functional and growth analysis showed that microbiome recovery is supported by enrichment in carbohydrate degradation and energy production capabilities. Association rule mining on 782 microbiome profiles from the MEDUSA database enabled reconstruction of the gut microbial ‘food-web’, identifying many recovery-associated bacteria (RABs) as primary colonizing species, with the ability to use both host and diet-derived energy sources, and to break down complex carbohydrates to support the growth of other bacteria. Experiments in a mouse model recapitulated the ability of RABs (Bacteroides thetaiotamicron and Bifidobacterium adolescentis) to promote microbiome recovery with synergistic effects, providing a two orders of magnitude boost to microbial abundance in early time-points and faster maturation of microbial diversity. The identification of specific microbial factors promoting microbiome recovery opens up opportunities for rationally fine-tuning pre- and probiotic formulations that prevent pathogen colonization and promote gut health.

Download Full-text

Structural analysis of the photosynthetic membrane from Ectothiorhodospira halochloris

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010007727x ◽

1983 ◽

Vol 41 ◽

pp. 740-741

Author(s):

H. Engelhardt ◽

R. Guckenberger ◽

W. Baumeister

Keyword(s):

Lattice Structure ◽

Bacterial Species ◽

Hexagonal Lattice ◽

Reaction Centre ◽

Photosynthetic Membrane ◽

Rhodopseudomonas Viridis ◽

Photosynthetic Membranes ◽

Ectothiorhodospira Halochloris ◽

Main Components

Bacterial photosynthetic membranes contain, apart from lipids and electron transport components, reaction centre (RC) and light harvesting (LH) polypeptides as the main components. The RC-LH complexes in Rhodopseudomonas viridis membranes are known since quite seme time to form a hexagonal lattice structure in vivo; hence this membrane attracted the particular attention of electron microscopists. Contrary to previous claims in the literature we found, however, that 2-D periodically organized photosynthetic membranes are not a unique feature of Rhodopseudomonas viridis. At least five bacterial species, all bacteriophyll b - containing, possess membranes with the RC-LH complexes regularly arrayed. All these membranes appear to have a similar lattice structure and fine-morphology. The lattice spacings of the Ectothiorhodospira haloohloris, Ectothiorhodospira abdelmalekii and Rhodopseudomonas viridis membranes are close to 13 nm, those of Thiocapsa pfennigii and Rhodopseudomonas sulfoviridis are slightly smaller (∼12.5 nm).

Download Full-text

Fine-Tuning Futures

ASHA Leader ◽

10.1044/leader.fq.22062017.np ◽

2017 ◽

Vol 22 (6) ◽

Author(s):

Christi Miller

Keyword(s):

Fine Tuning

Download Full-text

Food Safety Security: A new Concept for Enhancing Food Safety Measures

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000114 ◽

2012 ◽

Vol 82 (3) ◽

pp. 216-222 ◽

Cited By ~ 4

Author(s):

Venkatesh Iyengar ◽

Ibrahim Elmadfa

Keyword(s):

Food Safety ◽

Hazard Analysis ◽

Warning System ◽

Shared Responsibility ◽

Fine Tuning ◽

Strategic Action ◽

Surveillance Network ◽

Measurement Systems ◽

Critical Control Points ◽

The Impact

The food safety security (FSS) concept is perceived as an early warning system for minimizing food safety (FS) breaches, and it functions in conjunction with existing FS measures. Essentially, the function of FS and FSS measures can be visualized in two parts: (i) the FS preventive measures as actions taken at the stem level, and (ii) the FSS interventions as actions taken at the root level, to enhance the impact of the implemented safety steps. In practice, along with FS, FSS also draws its support from (i) legislative directives and regulatory measures for enforcing verifiable, timely, and effective compliance; (ii) measurement systems in place for sustained quality assurance; and (iii) shared responsibility to ensure cohesion among all the stakeholders namely, policy makers, regulators, food producers, processors and distributors, and consumers. However, the functional framework of FSS differs from that of FS by way of: (i) retooling the vulnerable segments of the preventive features of existing FS measures; (ii) fine-tuning response systems to efficiently preempt the FS breaches; (iii) building a long-term nutrient and toxicant surveillance network based on validated measurement systems functioning in real time; (iv) focusing on crisp, clear, and correct communication that resonates among all the stakeholders; and (v) developing inter-disciplinary human resources to meet ever-increasing FS challenges. Important determinants of FSS include: (i) strengthening international dialogue for refining regulatory reforms and addressing emerging risks; (ii) developing innovative and strategic action points for intervention {in addition to Hazard Analysis and Critical Control Points (HACCP) procedures]; and (iii) introducing additional science-based tools such as metrology-based measurement systems.

Download Full-text