Drug resistance plasmids

Conclusion The discovery of chemotherapeutic agents brought remarkable progress to the practice of medicine and to human and animal hygiene. In addition, improved sanitation and preventive medicine have protected human beings from infectious diseases caused by known pathogenic bacteria. As a result, the types of bacteria that play leading roles in infectious diseases have changed. These microoganisms readily cause infection, they are parasitic, and they carry multiple drug resistance as a result of the use of chemotherapeutic agents. Thus, mutiply resistant organisms have become prevalent and particular strains have become stabilized in hospitals and farms.The presence of conjugative (R) and nonconjugative (r) resistance plasmids in these bacterial strains has compounded the problems for the practice of medicine, livestock hygiene, and the fish culture industry. Rapid acquisition of drug resistance by bacteria and delays in finding new drugs have created new biological hazards for human beings.The discovery of resistance plasmids opened new research fields in genetics and molecular biology; it became clear that multiply resistant bacteria could develop quickly and spread rapidly all over the world. The genes governing replication, self-regulation, conjugal transmission and drug resistance, including transposon, are the most fascinating problems in biology. And the prevalence of drug resistance plasmids has broadened our perspective on the role that genetic exchanges play in the natural history of bacterial species.     

Drug resistance in schistosomes

Drug resistance in schistosomes is confined essentially to compounds of the hyconthone/oxamniquine family, since no documented case of resistance has so far been reported for the widely used drug praziquantel. The availability of strains of Schistosoma mansoni that are resistant to hyconthone and oxomniquine has permitted a detailed genetic and biochemical study of the mechanism of action of these compounds. Drugs must be activated by enzymatic esterification and this ultimately results in the production of an electrophilic moiety capable of alkylating DNA and other parasite macromolecules. As reviewed here by Donato Cioli, Livia Pica-Mattoccia and Sydney Archer, resistance is due to the loss of a drug-activating enzyme that is present in sensitive schistosomes and absent in resistant worms and in the mammalian hosts. Further study of this enzyme may yield valuable clues for drug design and for a basic understanding of parasite metabolism.     

Drug resistance in salmonellae

The medicinal resistance of salmonellae isolated in the USSR and the Slovak Republic in 1987-1988 was studied. The resistance of salmonellae at this period was shown to decrease in comparison with the period of 1985-1986. The study revealed the presence of multiresistant strains capable of the conjugative transmission of some resistance markers. The minimal inhibiting concentrations of antibiotics to which salmonellae proved to be resistant were determined.     

Drug resistance and Giardia

Giardiasis is a worldwide disease that can cause serious morbidity. Metronidozole is the current recommended drug for treatment, and is mostly still effective. However, Giardia duodenalis, the causative agent, is capable of developing resistance to high levels of metronidozole and other drugs, in vitro, via a number of mechanisms. Resistance, in vivo, has been reported and many cases of treatment failure have been variously attributed to a number of causes, including resistance. Here, Jacqueline and Peter Upcroft ask: is this the beginning of another chapter of drug resistance? or is the situation likely to remain as a 'few refractory cases'? Should we wait to find out or can we act positively to avert the possibility of yet another valuable drug in our limited pharmacopoeia becoming obsolete?     

肠球菌属细菌感染耐药性分析

目的 了解中国医科大学附属盛京医院肠球菌属细菌的临床分布及耐药情况,为指导临床制定合理有效治疗方案提供理论依据。方法 收集2017年1月1日至2017年12月31日我院门诊、住院患者肠球菌属细菌病原学资料,回顾性分析其菌种分布、标本分布、科室来源及其耐药特征。结果 共分离出466株肠球菌属细菌,其中粪肠球菌211株（45.28%）、屎肠球菌255株（54.72%）。肠球菌属细菌均以尿液标本为最主要的来源,其次为全血标本,并且来源于尿液标本的肠球菌属细菌对临床常用抗生素的耐药率普遍高于非尿液标本肠球菌属细菌耐药率。儿科为屎肠球菌最主要的分布科室,而粪肠球菌则主要分布于泌尿外科。耐药性方面,除四环素、利福平和喹努普汀/达福普汀外,屎肠球菌对受检的其余18种抗生素的耐药性均高于粪肠球菌,但对喹努普汀/达福普汀无耐药性,而粪肠球菌对此种抗生素的耐药率却为100.00%。二者对克林霉素的耐药率均为100.00%。共检出耐万古霉素肠球菌7株（1.50%）,耐替考拉宁肠球菌6株（1.28%）,未发现对替加环素、利奈唑胺耐药菌株。结论 屎肠球菌在肠球菌属细菌中占主要地位,且耐药率方面明显高于粪肠球菌,耐糖肽类抗生素菌株的出现需引起临床的高度警惕,应进一步加强耐药菌株的监测,并对临床应用抗生素加以规范。     

Drug resistance inYarrowia lipolytica

Six strains ofYarrowia lipolytica tested here were resistant to 10–20 g erythromycin or chloramphenicol per L glycerol-agar medium. Cells tolerating 4 g chloramphenicol per L were very rare and reverted rapidly to the highest resistance. In analogy with Ery^R mutants ofKluyveromyces lactis, our strains did not grow at 36°C but did not lose their viability at that temperature. Two levels of resistance were found with oligomycin and antimycin A,i.e. 10 and 3 mg/L in the former and 10 and 2 mg/L in the latter. The higher resistance levels segregated mitotically and were, therefore, controlled extrachromosomally. The lower resistance levels showed very frequent changes from sensitivity to resistance that prevented the genetic analysis of this resistance. An almost continuous range of tolerance to <5–400 μg mucidin per L was found in populations of the strains analyzed. Newly formed Muc^R cells were established only in the presence of the antibiotic. Pure cultures of Muc^R cells showed an extremely high instability caused by their lower viability and very low growth rate in the absence of mucidin. No loss of resistance to antimycin A was found, although Ant^R cells revealed similar negative selection. Mutability Muc^S»Muc^R and Muc^R»Muc^S was higher in Ant^R cells than in Ant^S ones.     

Drug resistance in Chromobacterium violaceum

Chromobacterium violaceum is a free-living bacterium commonly found in aquatic habitats of tropical and subtropical regions of the world. This bacterium is able to produce a large variety of products of biotechnological and pharmacological use. Although C. violaceum is considered to be non-pathogenic, some cases of severe infections in humans and other animals have been reported. Genomic data on the type strain ATCC 12472(T) has provided a comprehensive basis for detailed studies of pathogenicity, virulence and drug resistance genes. A large number of open reading frames associated with various mechanisms of drug resistance were found, comprising a remarkable feature of this organism. Amongst these, beta-lactam (penicillin and cephalosporin) and multidrug resistance genes (drug efflux pumps) were the most numerous. In addition, genes associated with bacitracin, bicyclomycin, chloramphenicol, kasugamycin, and methylenomycin were also found. It is postulated that these genes contribute to the ability of C. violaceum to compete with other bacteria in the environment, and also may help to explain the common drug resistance phenotypes observed in infections caused by this bacterium.     

Drug resistance in veterinary helminths

At present, there is no effective alternative to chemical control of parasitic helminths where livestock are grazed intensively. Resistance to anthelmintics has become a major problem in veterinary medicine, and threatens both agricultural income and animal welfare. The molecular and biochemical basis of this resistance is not well understood. The lack of reliable biological and molecular tests means that we are not able to follow the emergence and spread of resistance alleles and clinical resistance as well as we need. This review summarizes some of the recent findings on resistance mechanisms, puts forward some recommendations for limiting its impact and suggests some priorities for research in this area.     

Drug resistance of Mycobacterium tuberculosis]

Drug resistance of Mycobacterium tuberculosis was followed up within a period of 1986 to 1989. There was a tendency to stabilization of resistance to streptomycin (42 per cent), tubazid (45.2 per cent) and ethionamide (up. to 1.4 per cent). Resistance to kanamycin slowly increased (by 3 to 6 per cent every year). Resistance to rifampicin markedly increased (almost 15 times). Resistance to ethambutol decreased (10 times). It was shown that the drug resistance could be lowered by using the drug combinations.     

Drug resistance in tuberculosis--a reinfection model

There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting.     

喹诺酮外排泵耐药基因oqxAB的耐药机制及其流行情况

oqx AB是编码Oqx AB外排泵蛋白的多重耐药基因,由2个开放阅读框oqx A和oqx B组成,其主要介导细菌对喹诺酮类药物的耐药。该基因最早是在大肠埃希菌pOLA52质粒上被发现,是质粒介导的喹诺酮耐药基因的重要成员之一。目前已经分别发现了11个oqxA和32个oqxB等位基因。oqxAB通过质粒进行水平传播,使受体菌株容易形成耐药性,增加了临床治疗的难度。该基因目前主要流行于肠杆菌科,但不能排除也存在于非肠杆菌科细菌,给人类与家畜健康造成巨大的威胁。本文综述了喹诺酮外排泵耐药基因oqxAB及其等位基因的发现、耐药机制、国内外流行特点,以期为临床和畜牧生产中合理使用喹诺酮类抗菌药物,减少oqxAB基因的流行提供资料。