Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

Benchmarking of Homojunction Strained-Si NW Tunnel FETs for Basic Analog Functions

This paper reports a compact ambipolar model for homojunction strained-silicon (sSi) nanowire (NW) tunnel FETs (TFETs) capable of accurately describing both I-V and G-V characteristics in all regimes of operation, n- A nd p-ambipolarity, the superlinear onset of the output characteristics, and the temperature dependence. Experimental calibration on long channel (350 nm) complementary n- A nd p-type sSi NW TFETs has been performed to create the model, which is used to systematically benchmark the main analog figures of merit at device level: Gm/Id, gm/gds, fT and fT/Id Vd, and their temperature dependence from 25 °C to 125 °C. This allows for a direct comparison between 28-nm low-power Fully Depleted Silicon on Insulator (FD-SOI) CMOS node and 28-nm double-gate (DG) TFET. We demonstrate unique advantages of sSi DG TFET over CMOS, in terms of: 1) reduced temperature dependence of subthreshold swing; 2) higher transconductance per unit of current with peaks close to 40 V-1, for currents lower than 10 nA/μm; and 3) higher unity gain frequency per unit power for currents below 10 nA/μm}

Acute febrile myalgia in Vietnam due to trichinellosis following the consumption of raw pork.

Trichinellosis outbreaks occur occasionally in Vietnam following the consumption of undercooked pork. Diagnosing trichinella can be problematic because fever and myalgia are nonspecific, and diagnosis may be delayed. We describe 5 Vietnamese patients in whom trichinellosis was diagnosed after several weeks of illness