Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives

Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis. They are also used to detect resistance in tuberculosis cases with risk factors, in combination with genotypic tests. In low-income countries, genotypic methods screening hot-spot mutations known to confer resistance were found to be easier to perform because they avoid the culture and biosafety constraint. Given that genotypic tests can rapidly detect the prominent mechanisms of resistance, such as the rpoB mutation for rifampicin resistance, we are facing new challenges with the observation of false-resistance (mutations not conferring resistance) and false-susceptibility (mutations different from the common mechanism) results. Phenotypic and genotypic approaches are therefore complementary for obtaining a high sensitivity and specificity for detecting drug resistances and susceptibilities to accurately predict MDR/XDR cure and to gather relevant data for resistance surveillance. Although AST-MTB was established in the 1960s, there is no consensus reference method for MIC determination against which the numerous AST-MTB techniques can be compared. This information is necessary for assessing in vitro activity and setting breakpoints for future anti-tuberculosis agents

On dispersive energy transport and relaxation in the hopping regime

A new method for investigating relaxation phenomena for charge carriers hopping between localized tail states has been developed. It allows us to consider both charge and energy {\it dispersive} transport. The method is based on the idea of quasi-elasticity: the typical energy loss during a hop is much less than all other characteristic energies. We have investigated two models with different density of states energy dependencies with our method. In general, we have found that the motion of a packet in energy space is affected by two competing tendencies. First, there is a packet broadening, i.e. the dispersive energy transport. Second, there is a narrowing of the packet, if the density of states is depleting with decreasing energy. It is the interplay of these two tendencies that determines the overall evolution. If the density of states is constant, only broadening exists. In this case a packet in energy space evolves into Gaussian one, moving with constant drift velocity and mean square deviation increasing linearly in time. If the density of states depletes exponentially with decreasing energy, the motion of the packet tremendously slows down with time. For large times the mean square deviation of the packet becomes constant, so that the motion of the packet is ``soliton-like''.Comment: 26 pages, RevTeX, 10 EPS figures, submitted to Phys. Rev.

Optical absorption and activated transport in polaronic systems

We present exact results for the optical response in the one-dimensional Holstein model. In particular, by means of a refined kernel polynomial method, we calculate the ac and dc electrical conductivities at finite temperatures for a wide parameter range of electron phonon interaction. We analyze the deviations from the results of standard small polaron theory in the intermediate coupling regime and discuss non-adiabaticity effects in detail.Comment: 7 pages, 8 figure

Extended Infrared Photoresponse in Te-Hyperdoped Si at Room Temperature

Presently, silicon photonics requires photodetectors that are sensitive in a broad infrared range, can operate at room temperature, and are suitable for integration with the existing Si-technology process. Here, we demonstrate strong room-temperature sub-band-gap photoresponse of photodiodes based on Si hyperdoped with tellurium. The epitaxially recrystallized Te-hyperdoped Si layers are developed by ion implantation combined with pulsed-laser melting and incorporate Te-dopant concentrations several orders of magnitude above the solid solubility limit. With increasing Te concentration, the Te-hyperdoped layer changes from insulating to quasi-metallic behavior with a finite conductivity as the temperature tends to zero. The optical absorptance is found to increase monotonically with increasing Te concentration and extends well into the mid-infrared range. Temperature-dependent optoelectronic photoresponse unambiguously demonstrates that the extended infrared photoresponsivity from Te-hyperdoped Si p-n photodiodes is mediated by a Te intermediate band within the upper half of the Si band gap. This work contributes to pave the way toward establishing a Si-based broadband infrared photonic system operating at room temperature.Comment: 18 pages, 7 figure

Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase

In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB, the helicase uvrD1 and a double knock-out lacking both proteins were constructed and their sensitivity to a series of DNA damaging agents wa analysed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and inter-strand cross-links. In addition, it could be shown to exert a protective effect against oxidising and nitrosating agents. Interestingly, inactivation of uvrB and uvrD1 significantly increased marker integration frequencies in gene conversion assays. This implies that in mycobacteria, which lack the postreplicative mismatch repair system, NER, and particularly the UvrD1 helicase, is involved in the processing of a subset of recombination-associated mismatches

Episodic Rainfall Influences the Distribution and Abundance of the Regular Sea Urchin Lytechinus variegatus in Saint Andrew Bay, Northern Gulf of Mexico

The distribution and abundance of Lytechinus variegatus (Lamarck) were determined at three shallow-water stations in Saint Andrew Bay, FL, in the northern Gulf of Mexico. Populations were monitored at 4-mo intervals from Aug. 1997 to Aug. 1999 along 2- X 10-m transects, with four transects at each station. In Aug. 1997 individuals ranged in size from 15- to 63-mm diameter (mean = 38 mm; density= 1.4 individuals (ind.) m-2) at Station 1 (Stations 2 and 3 were not sampled on that date). By Oct. 1997 individuals at Station 1 ranged in size from 26 to 62 mm (mean = 48 mm; density = 0.6 ind. m-2), suggesting the growth of individuals within the population. At Station 2, individuals ranged between 50 and 70 mm (mean = 59 mm; densities = 1.0 ind. m-2) and at Station 3 between 30 and 79 mm (mean= 51 mm; densities = 1.4 ind, m-2) in Oct. 1997, indicating a population with no recent recruits. A mass mortality event was observed in April 1998 and was attributed to reduced salinities resulting from above-average rainfall in the previous month. Sea urchins were absent at Stations 1 and 2, whereas at Station 3 postdisturbance recruits were smaller (mean = 28 mm) and densities lower. Sea urchin tests were also observed at beach stations proximate to Stations 1 and 2. By July 1998 the populations had partially recovered at Stations 2 and 3 (densities = 0.6 and 1.1 ind. m-2, respectively), but test diameters were small at both stations. Test diameters had increased in Dec. 1998 at Station 3 when compared with those of July, but individuals at Station 2 showed overall smaller test diameters (mean = 28 mm), and densities had decreased again, presumably after another mass mortality caused by another major rainfall in Sep. In April 1999 test diameters had decreased further at Stations 2 and 3, indicating emigration or death of larger animals. We suggest that the shallow-water Saint Andrew Bay population of L. variegatus is reduced for several years at a time by episodic heavy rainfalls. This observation emphasizes the importance of density-independent processes controlling the distribution and abundance of marine organisms