Mechanisms of drug resistance and reversal of the resistance

The mechanisms for the resistance to anticancer agents have been vigorously studied and many factors that are involved in the resistance were found. Among the members of ABC transporter superfamily, P-glycoprotein, MRP1-5 and BCRP are involved in the drug resistance. LRP, identified as the major vault protein, is also related to drug resistance.     

Components of partial resistance as criteria for identifying resistance

The components of partial resistance, incubation period, lesion area, latent period and sporulation were recorded on plants of six winter and two spring wheat cultivars which had been artificially inoculated with Septoria nodorum spores. Incubation period gave a guide as to how the cultivars would respond in the field to Septoria nodorum but statistical analysis showed that it could not be used alone to predict accurately the resistance of each cultivar to the pathogen. Average sporulation, however, could be used with more confidence for predicting the field resistance of the cultivars. From a regression analysis of NIAB rating versus incubation period, lesion area, latent period and sporulation, an equation was devised to obtain resistance indices for each cultivar. These resistance indices clearly reflected the NIAB ratings for the cultivars. It would therefore appear that resistance indices could be used as a pre-field evaluation method for identifying resistance to Septoria nodorum and thus be a valuable technique in breeding programmes.     

Hydraulic resistance of two sorghums varying in drought resistance

Genotypes of sorghum [Sorghum bicolor (L.) Moench] vary in drought resistance. Yet it is not known if their hydraulic resistances vary. The objective of this study was to determine if the hydraulic resistance of a drought-resistant sorghum was the same as that of a drought-sensitive sorghum. Leaf water and osmotic potentials were measured daily, during a 14-d period, in leaves of a drought-resistant (‘KS9’) and a drought-sensitive (‘IA25’) sorghum, which had the roots in pots with a commercial potting soil that was either well watered or allowed to dry. Soil water potential, adaxial stomatal resistance, and transpiration rate were determined daily. Hydraulic resistance of the plants was calculated from the slope of the line relating soil water potential minus leaf water potential versus transpiration rate. When the soil was not watered, the drought-sensitive sorghum had a water potential that averaged −0.50 MPa lower and an osmotic potential that averaged −0.57 MPa lower, but a similar adaxial stomatal resistance (1.19 s mm⁻¹), compared with the drought-resistant sorghum. Seven days after the beginning of the experiment, the water potential of the soil with the drought-sensitive sorghum was −0.25 MPa lower than that of the soil with the drought-resistant sorghum. With the water-limited conditions, the drought-sensitive sorghum depleted the soil-water reserve more quickly and died 2 d before the drought-resistant sorghum. Under well watered conditions, the two sorghums had similar water potentials (−1.64 MPa), osmotic potentials (−2.83 MPa), and adaxial stomatal resistances (0.78 s mm⁻¹). The calculated hydraulic resistance of the two sorghums did not differ and averaged 3.4 × 10⁷ MPa s m⁻¹. The results suggested that the variation in susceptibility to drought between the two genotypes was due to differences in rate of soil-water extraction. Contribution No. 86-249-J from the Kansas Agricultural Experiment Station. The paper is dedicated to the memory of Dr Dan M Rodgers.     

Costs of resistance

Studies of the reduction of fitness in plants expressing resistance characteristics have always been popular. New techniques for manipulating defense expression have recently resulted in a greater understanding of the mechanisms through which different types of resistance strategies produce costs, especially those costs associated with inducible defenses.     

The evolution of resistance genes in multi-protein plant resistance systems

The genomic perspective aids in integrating the analysis of single resistance (R-) genes into a higher order model of complex plant resistance systems. The majority of R-genes encode a class of proteins with nucleotide binding (NB) and leucine-rich repeat (LRR) domains. Several R-proteins act in multi-protein R-complexes that mediate interaction with pathogen effectors to induce resistance signaling. The complexity of these systems seems to have resulted from multiple rounds of plant-pathogen co-evolution. R-gene evolution is thought to be facilitated by the formation of R-gene clusters, which permit sequence exchanges via recombinatorial mispairing and generate high haplotypic diversity. This pattern of evolution may also generate diversity at other loci that contribute to the R-complex. The rate of recombination at R-clusters is not necessarily homogeneous or consistent over evolutionary time: recent evidence suggests that recombination at R-clusters is increased following pathogen infection, suggesting a mechanism that induces temporary genome instability in response to extreme stress. DNA methylation and chromatin modifications may allow this instability to be conditionally regulated and targeted to specific genome regions. Knowledge of natural R-gene evolution may contribute to strategies for artificial evolution of novel resistance specificities.     

Determination of antibiotic resistance and resistance plasmids of clinical Enterococcus species

To determine the antibiotic resistance pattern and resistance plasmids, we studied 23 antibiotic-resistant clinical isolates of Enterococcus spp. which caused infection in Bayindir-Ankara Hospital, Turkey. Biochemical and physiological identification tests were applied by the Vitek system and compared with the results of protein profiles by SDS-PAGE. From 23 isolates, 20 were identified as E. faecalis, 2 as E. faecium and 1 as E. gallinarum. Twenty four antibiotics belong to 10 different groups were used in susceptibility tests. Multiple antibiotic resistance was determined in 10 of 23 Enterococcus spp. Overall resistance to the used antibiotics was 47.3% and low level resistance was 16.6%. Among the isolates tested, 8.7% demonstrated high level gentamicin resistance, 17.4% demonstrated high level streptomycin resistance, and 43.5% demonstrated penicillin resistance. High level vancomycin resistant Enterococcus spp. rate was 34.8%, and 60.9% exhibited low level resistance to vancomycin and teicoplanin. They contain plasmids which varied in numbers between 1 and 11 and the plasmid sizes ranged from 2.08 to 56.15 kb. In curing experiments with acriflavine, two different plasmids were shown in different molecular sizes of 33.49 and 13.6 kb while the first determined glycopeptide and penicillin resistance, the second one determined either glycopeptide or penicillin resistance in two different E. faecalis strains. On the other hand, a 22.58 kb plasmid, determining kanamycin resistance, was detected in an E. faecium strain. After the curing experiments, an elimination of 37.17 and 44.47 kDa protein bands was shown in E. faecium EFA1 and E. faecalis EFA13 in SDS-PAGE, respectively. This survey indicates the increase of antibiotic-resistant enterococci, especially to vancomycin in our hospital isolates.     

Infectious plasmid resistance and efflux pump mediated resistance

Various bacterial plasmids can be eliminated from bacterial species cultured as pure or mixed bacterial cultures by non-mutagenic heterocyclic compounds at subinhibitory concentrations. For plasmid curing, the replication should be inhibited at three different levels simultaneously: the intracellular replication of plasmid DNA, partition and intercellular transconjugal transfer. The antiplasmid action of the compounds depends on the chemical structure. The targets for antiplasmid compounds were analysed in detail. It was found that amplified extrachromosomal DNA in the superhelical state binds more drug molecules than does the linear or open-circular form of the plasmid or the chromosome, without stereospecificity which leads to functional inactivation of the extrachromosomal genetic code. Plasmid elimination also occurs in ecosystems containing numerous bacterial species simultaneously, but the elimination of antibiotic resistance-encoding plasmids from all individual cells of the population is never complete. The medical significance of plasmid elimination in vitro is, it provides a method to isolate plasmid-free bacteria for biotechnology without any risk of mutations, and it opens up a new perspective in rational drug design against bacterial plasmids. Hypothetically, the combination of antiplasmid drugs and antibiotics may improve the effectivity of antibiotics against resistant bacteria; therefore, the results cannot be exploited until the curing efficiency reaches 100%. Inhibition of the conjugational transfer of antibiotic resistance plasmids can be exploited to reduce the spreading of these plasmids in ecosystems.     

山西省黍稷种质资源抗倒性鉴定及相关形态特征研究

黍稷种质的倒伏是造成黍稷减产的一大要素,如何防止黍稷的倒伏,筛选和培育抗倒的种质是解决黍稷倒伏最根本和有效的方法。通过对山西省的1192份黍稷种质资源进行抗倒性鉴定,筛选出71份高抗倒的种质。同时对高抗倒种质和不抗倒种质茎、根的形态特征进行了比较研究,证明黍稷种质的抗倒性与茎、根的形态特征有密切关系,高抗倒种质在茎、根形态特征上所占的优势是形成高抗倒的重要原因。     

Ivermectin resistance

In this review of ivermectin resistance, Wesley Shoop discusses the definition of resistance, catalogs all known cases of ivermectin resistance, argues that overmectins and milbemycins belong in the same action family, discusses the possibility of resistance in the filariae, and suggests that detection of ivermectin resistance is the area where future research is most needed.     

Resisting resistance

This month's Genome Watch describes how knowledge of the malaria parasite genome can be used to better understand and mitigate the emergence of drug resistance.     

Nematode resistance

Plant-parasitic nematodes are major pests of both temperate and tropical agriculture. Many of the most damaging species employ an advanced parasitic strategy in which they induce redifferentiation of root cells to form specialized feeding structures able to support nematode growth and reproduction over several weeks. Current control measures, particularly in intensive agriculture systems, rely heavily on nematicides but alternative strategies are required as effective chemicals are withdrawn from use. Here, we review the different approaches that are being developed to provide resistance to a range of nematode species. Natural, R gene-based resistance is currently exploited in traditional breeding programmes and research is ongoing to characterize the molecular basis for the observed resistant phenotypes. A number of transgenic approaches hold promise, the best described being the expression of proteinase inhibitors to disrupt nematode digestion. The application of plant-delivered RNA interference (RNAi) to silence essential nematode genes has recently emerged as a potentially valuable resistance strategy.