Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden.

We characterized clinically occurring and novel mutations in the ß subunit of RNA polymerase in Clostridium difficile (CdRpoB), conferring rifamycin (including rifaximin) resistance. The Arg505Lys substitution did not impose an in vitro fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of CdRpoB. In general, most mutations lacked in vitro fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic.

Poly(3-octylthiophene)/fullerene heterojunction solar cell incorporating carbon nanotubes.

Here, we report incorporation of multiwalled carbon nanotubes (MWNTs) in Poly(3-octylthiophene)/fullerene heterojunction solar cells. Multi-walled carbon nanotubes (MWNTs) were functionalized by oxygen plasma treatment. Photoelectron spectroscopy study of oxygen plasma treated MWNTs shows surface modification with hydroxyl and carboxyl groups. Plasma treated MWNTs were combined with Poly(3-octylthiophene) and solar cell was fabricated with the structure Au/P3OT + MWNTs/C60/FTO. Fabricated device shows short circuit current density (Jsc) open circuit voltage (Voc), fill factor and conversion efficacy as 0.04 mA/cm2, 0.355 V, 21% and 0.003%. Solar cell fabricated with incorporation of MWNTs shows much better device performance, then that of the device without MWNTs. MWNTs in the polymer composite act as exciton dissociation site and provide efficient hole transportation, and thereby improving device performance.

Direct Synthesis of Large-Area Graphene on Insulating Substrates at Low Temperature using Microwave Plasma CVD.

With a combination of outstanding properties and a wide spectrum of applications, graphene has emerged as a significant nanomaterial. However, to realize its full potential for practical applications, a number of obstacles have to be overcome, such as low-temperature, transfer-free growth on desired substrates. In most of the reports, direct graphene growth is confined to either a small area or high sheet resistance. Here, an attempt has been made to grow large-area graphene directly on insulating substrates, such as quartz and glass, using magnetron-generated microwave plasma chemical vapor deposition at a substrate temperature of 300 °C with a sheet resistance of 1.3k Ω/□ and transmittance of 80%. Graphene is characterized using Raman microscopy, atomic force microscopy, scanning electron microscopy, optical imaging, UV-vis spectroscopy, and X-ray photoelectron spectroscopy. Four-probe resistivity and Hall effect measurements were performed to investigate electronic properties. Key to this report is the use of 0.3 sccm CO2 during growth to put a control over vertical graphene growth, generally forming carbon walls, and 15-20 min of O3 treatment on as-synthesized graphene to improve sheet carrier mobility and transmittance. This report can be helpful in growing large-area graphene directly on insulating transparent substrates at low temperatures with advanced electronic properties for applications in transparent conducting electrodes and optoelectronics.

Action of nitroheterocyclic drugs against Clostridium difficile.

The nitroheterocyclic classes of drugs have a long history of use in treating anaerobic infections, as exemplified by metronidazole as a first-line treatment for mild-to-moderate Clostridium difficile infection (CDI). Since direct comparisons of the three major classes of nitroheterocyclic drugs (i.e. nitroimidazole, nitazoxanide and nitrofurans) and nitrosating agents against C. difficile are under-examined, in this study their actions against C. difficile were compared. Results show that whilst transient resistance occurs to metronidazole and nitazoxanide, stable resistance arises to nitrofurans upon serial passage. All compounds killed C. difficile at high concentrations in addition to the host defence nitrosating agent S-nitrosoglutathione (GSNO). This suggests that GSNO killing of C. difficile contributes to its efficacy in murine CDI. Although nitric oxide production could not be detected for the nitroheterocyclic drugs, the cellular response to metronidazole and nitrofurans has some overlap with the response to GSNO, causing significant upregulation of the hybrid-cluster protein Hcp that responds to nitrosative stress. These findings provide new insights into the action of nitroheterocyclic drugs against C. difficile.

Syntheses and evaluation of macrocyclic engelhardione analogs as antitubercular and antibacterial agents.

The natural product engelhardione is an underexplored chemotype for developing novel treatments for bacterial infections; we therefore explored this natural product scaffold for chemical diversification and structure-activity relationship studies. Macrocyclic engelhardione and structural regioisomers were synthesized using a series of aldol condensations and selective hydrogenations to generate the 1,7-diarylheptan-3-one derivatives, followed by microwave-assisted intramolecular Ullmann coupling to afford a series of macrocyclic diaryl ether analogs. An extended macrocyclic chemical library was then produced by oxime formation, reductive amination and O-alkylation. Antibacterial evaluation revealed that the reductive amination derivatives 7b and 7d showed moderate activities (minimum inhibitory concentrations: 12.5-25 µg ml(-1)) against Mycobacterium tuberculosis and Gram-positive pathogens, as well as anti-Gram-negative activity against an efflux impaired Escherichia coli strain. These results provide validated leads for further optimization and development.