Antibiotic-resistant strains of pathogenic bacteria are increasingly prevalent in hospitals and the community. New antibiotics are needed to combat these bacterial pathogens, but progress in developing them has been slow. Historically, most antibiotics have come from a small set of molecular scaffolds whose functional lifetimes have been extended by generations of synthetic tailoring. The emergence of multidrug resistance among the latest generation of pathogens suggests that the discovery of new scaffolds should be a priority. Promising approaches to scaffold discovery are emerging; they include mining underexplored microbial niches for natural products, designing screens that avoid rediscovering old scaffolds, and repurposing libraries of synthetic molecules for use as antibiotics.

/pdf/antibiotics-for-emerging-pathogens-5btailsksh.pdf

Antibiotics For Emerging Pathogens

Although nosocomial infections by Staphylococcus epidermidis have gained much attention, this skin-colonizing bacterium has apparently evolved not to cause disease, but to maintain the commonly benign relationship with its host. Accordingly, S. epidermidis does not produce aggressive virulence determinants. Rather, factors that normally sustain the commensal lifestyle of S. epidermidis seem to give rise to additional benefits during infection. Furthermore, we are beginning to comprehend the roles of S. epidermidis in balancing the epithelial microflora and serving as a reservoir of resistance genes. In this Review, I discuss the molecular basis of the commensal and infectious lifestyles of S. epidermidis.

Staphylococcus epidermidis — the 'accidental' pathogen

Outer Membrane Permeability and Antibiotic Resistance

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases. The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=7300&context=open_access_pubs

The gut microbiome in atherosclerotic cardiovascular disease

The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascent core-lipid A is flipped to the outer surface of the inner membrane by the ABC transporter MsbA, where the O-antigen polymer is attached. Diverse covalent modifications of the lipid A moiety may occur during its transit from the outer surface of the inner membrane to the outer membrane. Lipid A modification enzymes are reporters for lipopolysaccharide trafficking within the bacterial envelope. Modification systems are variable and often regulated by environmental conditions. Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines.

Lipid a modification systems in gram-negative bacteria

https://www.cell.com/cell/pdf/S0092-8674(05)00553-2.pdf

Recognition of Antimicrobial Peptides by a Bacterial Sensor Kinase

A solution for scattering from thin dielectric disks has been obtained by approximating the currents induced inside the disk with the currents which would exist inside a dielectric slab of the same thickness, orientation and dielectric properties. This procedure yields an electrostatic approximation when the disk thickness T is small compared to the wavelength of the incident radiation and yields a conventional physical optics approximation when the dimension A , characteristic of the geometrical cross section of the disk, is large compared to wavelength. When the ratio A/T is sufficiently large one or the other of these approximations applies, regardless of the frequency of the incident radiation. Consequently, the solution provides a conventional approximation for the scattered fields at all kA . As a check on this conclusion, a comparison has been made between measurements of the radar cross section of thin dielectric disks and the cross sections predicted using this theory. Agreement was found for thin disks with both large and small values of kA .

/pdf/scattering-from-thin-dielectric-disks-4zywock81o.pdf

Scattering from thin dielectric disks

The Italian grape germplasm is characterized by a high level of richness in terms of varieties number, with nearly 600 wine grape varieties listed in the Italian National Register of Grapevine Varieties and with a plethora of autochthonous grapes. In the present study an extended SNP genotyping has been carried out on Italian germplasm of cultivated Vitis vinifera subsp. sativa and Vitis hybrids. Several hundred Italian varieties maintained in the repositories of scientific Institutions and about one thousand additional varieties derived from previous studies on European, Southern Italy, Magna Graecia and Georgian germplasm were considered. The large genotyping data obtained were used to check the presence of homonyms and synonyms, determine parental relationships, and identify the main ancestors of traditional Italian cultivars and closely-related accessions. The parentage among a set of 1,232 unique varieties has been assessed. A total of 92 new parent-offspring (PO) pairs and 14 new PO trios were identified. The resulted parentage network suggested that the traditional Italian grapevine germplasm originates largely from a few central varieties geographically distributed into several areas of genetic influence: "Strinto porcino" and its offspring "Sangiovese", "Mantonico bianco" and "Aglianico" mainly as founder varieties of South-Western Italy (IT-SW); Italian Adriatic Coast (IT-AC); and Central Italy with most varieties being offsprings of "Visparola", "Garganega" and "Bombino bianco"; "Termarina (Sciaccarello)" "Orsolina" and "Uva Tosca" as the main varieties of North-Western Italy (IT-NW) and Central Italy. The pedigree reconstruction by full-sib and second-degree relationships highlighted the key role of some cultivars, and, in particular, the centrality of "Visparola" in the origin of Italian germplasm appeared clear. An hypothetical migration of this variety within the Italian Peninsula from South to North along the eastern side, as well as of "Sangiovese" from South to Central Italy along the Western side might be supposed. Moreover, it was also highlighted that, among the main founders of muscat varieties, "Moscato bianco" and "Zibibbo (Muscat of Alexandria)" have spread over the whole Italy, with a high contribution by the former to germplasm of the North-Western of the peninsula.

/pdf/parentage-atlas-of-italian-grapevine-varieties-as-inferred-3rbzwas60b.pdf

Parentage Atlas of Italian Grapevine Varieties as Inferred From SNP Genotyping.

http://www.cchem.berkeley.edu/plggrp/papers/PLG2013e.pdf

Coexistence of fluid and crystalline phases of proteins in photosynthetic membranes.

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Recognition of Antimicrobial Peptides by a Bacterial Sensor Kinase

Scattering from thin dielectric disks

Scattering from thin dielectric disks

Parentage Atlas of Italian Grapevine Varieties as Inferred From SNP Genotyping.

Coexistence of fluid and crystalline phases of proteins in photosynthetic membranes.