Antibiotic resistance and resistance mechanisms in Campylobacter jejuni and Campylobacter coli

Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world and infections with these organisms occur more frequently than do infections due to Salmonella species, Shigella species, or Escherichia coli 0157:H7. The incidence of human Campylobacter infections has increased markedly in both developed and developing countries worldwide and, more significantly, so has the rapid emergence of antibiotic-resistant Campylobacter strains, with evidence suggesting that the use of antibiotics, in particular the fluoroquinolones, as growth promoters in food animals and the veterinary industry is accelerating this trend. In this minireview, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter spp are discussed.     

Imazaquin and chlorsulfuron resistance and cross resistance in mutants of Chlamydomonas reinhardtii

Summary Chlorsulfuron and/or imazaquin resistant mutants of Chlamydomonas reinhardtii strain CW15 have been obtained and shown to have actolactate synthase (ALS) with altered sensitivity to one or both of these herbicides. Herbicide resistance in the three mutants described is allelic, and resistance appears to result from a dominant or semidominant mutation in a single, nuclear gene. Imazaquin and chlorsulfuron resistant ALS from imazaquin and chlorsulfuron resistant mutants, together with single-gene Mendelian inheritance of these phenotypes, suggests that ALS is the sole site of action of the two herbicides in Chlamydomonas. A high degree of cross resistance between the two herbicides was found in only one mutant. This mutant (IM-13) was selected for resistance to imazaquin and has a high level of in vitro resistance to both imazaquin (270-fold increased I₅₀) and chlorsulfuron (900-fold increased I₅₀). In another mutant selected for resistance to imazaquin (IMR-2), hyper-sensitivity to chlorsulfuron was found. A mutant selected for resistance to chlorsulfuron (CSR-5), had a substantial degree of resistance of chlorsulfuron (80-fold increased I₅₀), but not to imazaquin (7-fold increased I₅₀).     

绿脓杆菌对鲎素耐受性特点及耐受性机制的研究

【目的】为了探讨鲎素作为抗菌药物在临床使用中的安全性问题,通过鲎素连续增高浓度法对绿脓杆菌进行耐受性诱导,并对其耐受性机制进行初步研究,以期为鲎素的广泛应用提供理论依据。【方法】绿脓杆菌ATCC27853为试验菌株,通过连续增高浓度诱导法筛选抗药菌株,并通过抗药稳定性、交叉抗药性、抗药性代偿测定来探究其耐受性特点,通过对其胞外蛋白酶活性、生物膜形成、胞外多糖含量的变化来探讨其抗药性机制。【结果】通过连续增高鲎素浓度法对原始菌株进行30多代诱导后,绿脓杆菌ATCC27853对鲎素的MIC值逐渐增高,80多代时产生了明显抗药性。抗药菌株对丁胺卡那以及pexiganan、鲎素同源肽tachyplesin III、polyphemusin I均能产生不同程度的抗药性。在无药培养基中抗药菌株以更长的延滞期作为抗药性代偿,但在有药培养基中具有更短的延滞期和更大的生长速率。抗药菌株较原始菌株分泌的胞外蛋白酶活性增高,并能降低鲎素的抗菌活性。在同样条件下抗药菌株较原始菌株胞外多糖含量增高,更易形成生物膜。【结论】在长期选择压力下绿脓杆菌ATCC27853对鲎素能产生抗药性,其抗药性机制可能与生物膜形成、胞外蛋白酶失活鲎素有关。关于细菌对鲎素的抗药性机制,有待进一步研究。     

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。     

Antimicrobial resistance and resistance plasmids in Salmonella from Ontario, Canada.

Collections of 589 human and 204 animal strains of Salmonella isolated in Ontario during the summer of1974 were examined for susceptibility to 12 antimicrobial agents. Many isolates were found to be resistant to both chloramphenicol (12.4% of the human and 38.2% of the animal sample) and ampicillin. The chloramphenicol resistance almost always occurred in strains which were also resistant to ampicillin and was usually due to a self-transmissible plasmid with a resistance pattern of CmKmSmTc (chloramphenicol, kanamycin, streptomycin, and tetracycline) or CmTc. Ampicillin resistance in these strains was mediated by a variety of plasmids with patterns ApSu (ampicillin and sulfa drugs) and ApSmSu, many of which were nonself-transmissible. Ampicillin resistance in chloramphenicol-sensitive strains was transferable from 21% of the strains, and it was associated with resistance patterns which were different from the self-transferable ampicillin patterns from the chloramphenicol-resistance strains.     

Antimicrobial resistance islands: resistance gene clusters in Salmonella chromosome and plasmids

Genes conferring simultaneous resistance to different classes of antimicrobials, confer a selective advantage to the host, particularly when those corresponding antibiotics are administered. Multiple resistance genes clustered within the same genetic locus (resistance island) can be transferred en bloc to other organisms. In this chapter we review novel multidrug resistance islands recently described in Salmonella.     

Edeine inhibition and resistance in Neurospora

To obtain data on the biochemical effects of edeine in the fungus Neurospora crassa, in vivo protein synthesis, in vitro protein synthesis, as well as in vivo RNA and DNA synthesis of the wildtype and an edeine resistant mutant were measured.—Incorporation of ³H leucine into conidia of both strains, which served as a measure for in vivo protein synthesis, was inhibited by 200 g edeine/ml as follows: Wildtype approx. 40%, mutant approx. 6%.—Incorporation of ¹⁴C phenylalanine into polyphenylalanine in a cell free system with ribosomes from either the wildtype or the mutant, was inhibited between 74 and 95% by edeine at a ratio of 2 molecules edeine per ribosome.—Incorporation of ³H adenosine into conidia, serving as a measure for in vivo RNA synthesis, was inhibited in the wild-type (approx. 30% inhibition by 200 g edeine/ml). It was, however, not influenced in the ed ^r mutant. Similarly, in vivo DNA synthesis was decreased in the wildtype, but not in the mutant.—These results suggest that edeine acts at more than one site. The resistance of the mutant ed ^r -29 (ed ^r -2 locus) is tentatively interpreted as due to a block in edeine uptake.     

Mupirocin resistance in staphylococci: development and transfer of isoleucyl-tRNA synthetase-mediated resistance in vitro

Mupirocin resistance could be transferred from highly resistant clinical isolates of Staphylococcus aureus to highly sensitive recipients of Staph. aureus, Staph. epidermidis and Staph. haemolyticus. Transconjugants of the latter two organisms could transfer this resistance into mupirocin-sensitive Staph. aureus. Moderately resistant strains did not transfer this resistance to sensitive recipients, nor did strains with high-level mupirocin resistance developed by serial transfer or habituation. The inhibitory effects of mupirocin on crude isoleucyl-tRNA synthetases (IRS) isolated from mupirocin-sensitive and -resistant strains of Staph. aureus have been determined. Drug concentrations needed to produce 50% inhibition, I50 values, were very low against IRS from a highly sensitive strain, somewhat higher against IRS from moderately resistant strains, much higher against enzyme from strains trained in vitro to high-level resistance, and considerably higher still against IRS extracted from clinical isolates possessing high-level mupirocin resistance and from the transconjugates of such strains resulting from crosses with mupirocin-sensitive strains. It is concluded that high-level resistance in clinical isolates is plasmid-mediated involving a second, mupirocin-resistant IRS whereas in moderately resistant strains, and in strains trained in vitro to high-level resistance, chromosomal mutations are likely to be responsible for decreasing IRS sensitivity.     

Melanism and disease resistance in insects

There is growing evidence that insects in high-density populations invest relatively more in pathogen resistance than those in low-density populations (i.e. density-dependent prophylaxis). Such increases in resistance are often accompanied by cuticular melanism, which is characteristic of the high-density form of many phase polyphenic insects. Both melanism and pathogen resistance involve the prophenoloxidase enzyme system. In this paper the link between resistance, melanism and phenoloxidase activity is examined in Spodoptera larvae. In S. exempta , cuticular melanism was positively correlated with phenoloxidase activity in the cuticle, haemolymph and midgut. Melanic S. exempta larvae were found to melanize a greater proportion of eggs of the ectoparasitoid Euplectrus laphygmae than non-melanic larvae, and melanic S. littoralis were more resistant to the entomopathogenic fungus Beauveria bassiana (in S. exempta the association between melanism and fungal resistance was non-signficant). These results strengthen the link between melanism and disease resistance and implicate the involvement of phenoloxidase.     

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.     

Mating increases starvation resistance and decreases oxidative stress resistance in Drosophila melanogaster females

Mating stimulates complex physiological changes in females of Drosophila melanogaster. Long-term effects of mating are manifested in increased fecundity and shortened lifespan. It is not clear how mating affects stress resistance in fly females. We addressed this question here and found that mated and highly fecund wild-type D. melanogaster females have significantly higher resistance to starvation throughout their lifetime than age-matched virgin females. Mean survival time under starvation was age dependent with maximum survival time observed in 15-day-old mated females. Mating-induced increase in starvation resistance was associated with significantly higher fat reserves stored as triacylglycerols. While mated females had higher resistance to starvation, their resistance to oxidative stress was significantly lower than in age-matched virgins. Our study revealed that mating leads to an opposing relationship between resistance to starvation and resistance to oxidative stress in Drosophila females. Thus, shortened lifespan of mated females is associated with their high-fat content and greater susceptibility to oxidative stress.     

Copper uptake and resistance in bacteria

Copper ions are essential for bacteria but can cause a number of toxic cellular effects if levels of free ions are not controlled. Investigations of copper-resistant bacteria have revealed several mechanisms, mostly plasmid-determined, that prevent cellular uptake of high levels of free copper ions. However, these studies have also revealed that bacteria apparently have efficient chromosomally encoded systems for uptake and management of trace levels of copper. This review will explore the relationship of copper uptake systems to resistance mechanisms and the possibility that copper resistance has evolved directly through modification of chromosomal copper uptake genes.     

Antimicrobial resistance in Campylobacter: Susceptibility testing methods and resistance trends

Most Campylobacter infections are self-limiting but antimicrobial treatment (e.g., macrolides, fluoroquinolones) is necessary in severe or prolonged cases. Susceptibility testing continues to play a critical role in guiding therapy and epidemiological monitoring of resistance. The methods of choice for Campylobacter recommended by the Clinical and Laboratory Standards Institute (CLSI) are agar dilution and broth microdilution, while a disk diffusion method was recently standardized by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Macrolides, quinolones, and tetracyclines are among the common antimicrobials recommended for testing. Molecular determination of Campylobacter resistance via DNA sequencing or PCR-based methods has been performed. High levels of resistance to tetracycline and ciprofloxacin are frequently reported by many national surveillance programs, but resistance to erythromycin and gentamicin in Campylobacter jejuni remains low. Nonetheless, variations in susceptibility observed over time underscore the need for continued public health monitoring of Campylobacter resistance from humans, animals, and food.     

Ceramides in insulin resistance and lipotoxicity

Obesity predisposes individuals to the development of insulin resistance in skeletal muscle and the liver, and researchers have recently proposed two mechanisms by which excess adiposity antagonizes insulin action in peripheral tissues. First, when adipocytes exceed their storage capacity, fat begins to accumulate in tissues not suited for lipid storage, leading to the formation of specific metabolites that inhibit insulin signal transduction. Second, obesity triggers a chronic inflammatory state, and cytokines released from either adipocytes or from macrophages infiltrating adipose tissue antagonize insulin action. The sphingolipid ceramide is a putative intermediate linking both excess nutrients (i.e. saturated fatty acids) and inflammatory cytokines (e.g. tumor necrosis factor-alpha, TNFalpha) to the induction of insulin resistance. Moreover, ceramide has been shown to be toxic in a variety of different cell types (e.g. pancreatic beta-cells, cardiomyocytes, etc.), and review of the literature reveals putative roles for the sphingolipid in the damage of cells and tissues which accompany diabetes, hypertension, cardiac failure, atherosclerosis, etc. In this review, I will evaluate the contribution of ceramides in the development of insulin resistance and the complications associated with metabolic diseases.     

Nutrition and disease resistance in fish

Disease resistance in fish encompasses a variety of mechanisms including maintenance of epithelial barriers and the mucus coat; nonspecific cellular factors such as phagocytosis by macrophages and neutrophils; nonspecific humoral factors such as lysozyme, complement, and transferrin; and specific humoral and cellular immunity. Numerous nutritional factors can significantly affect incidence and severity of a variety of infectious diseases. Individual micronutrients known to affect disease resistance include vitamins C, B₆, E, and A and the minerals iron and fluoride. Macronutrient (protein, lipid, and carbohydrate) levels have not been critically evaluated. There are indications that certain fatty acids may be important factors in disease resistance. The potential for dietary enhancement of disease resistance in fish culture certainly exists. Before this can be achieved, more information is required on pathogenesis and specific resistance mechanisms involved in individual diseases, the specific effects of various nutrients, and how these effects are modulated by other dietary components and environmental factors.     

Glyoxalase in tumourigenesis and multidrug resistance

Since the discovery by Warburg of high aerobic glycolysis in most tumours in the 1920s, it has remained unclear how to exploit this in chemotherapy. The aim of this review is to assess the evidence for the involvement of the glyoxalase system in tumour growth and multidrug resistance and the importance of the glyoxalase system as a target for anticancer drug development and a source of biomarkers for tumour diagnosis. Increased expression of glyoxalase 1 appears to support the viability of tumour cells with high glycolytic rates. Multidrug resistance conferred by overexpression of glyoxalase 1 suggests mechanisms of toxicity of most current antitumour agents involve, in some part, accumulation of methylglyoxal to cytotoxic levels. The recent finding of glyoxalase 1 gene amplification in tumours and induction of increased glyoxalase 1 expression by malignant transformation and conventional antitumour drug treatment implies a critical role of glyoxalase 1 in innate and acquired multidrug resistance in cancer treatment. Improved understanding of glyoxalase 1 in cancer chemotherapy multidrug resistance is likely vital to achieve improvement of cancer patient survival rates. Advances made to counter glyoxalase 1-linked multidrug resistance with glyoxalase 1 inhibitors and related prodrugs has been translated from in vitro to pre-clinical in vivo studies. Further research is required urgently for next stage clinical translation. Finally, overexpression of glyoxalase 1 may be linked to multidrug resistance in chemotherapy of other disease - such as microbial infections.