抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(14)61632-3/pdf

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

Origins and Evolution of Antibiotic Resistance

During the last three decades, the impact of chemical pollution has focused almost exclusively on the conventional "priority" pollutants, especially those acutely toxic/carcinogenic pesticides and industrial intermediates displaying persistence in the environment. This spectrum of chemicals, however, is only one piece of the larger puzzle in "holistic" risk assessment. Another diverse group of bioactive chemicals receiving comparatively little attention as potential environmental pollutants includes the pharmaceuticals and active ingredients in personal care products (in this review collectively termed PPCPs), both human and veterinary, including not just prescription drugs and biologics, but also diagnostic agents, "nutraceuticals," fragrances, sun-screen agents, and numerous others. These compounds and their bioactive metabolites can be continually introduced to the aquatic environment as complex mixtures via a number of routes but primarily by both untreated and treated sewage. Aquatic pollution is particularly troublesome because aquatic organisms are captive to continual life-cycle, multigenerational exposure. The possibility for continual but undetectable or unnoticed effects on aquatic organisms is particularly worrisome because effects could accumulate so slowly that major change goes undetected until the cumulative level of these effects finally cascades to irreversible change--change that would otherwise be attributed to natural adaptation or ecologic succession. As opposed to the conventional, persistent priority pollutants, PPCPs need not be persistent if they are continually introduced to surface waters, even at low parts-per-trillion/parts-per-billion concentrations (ng-microg/L). Even though some PPCPs are extremely persistent and introduced to the environment in very high quantities and perhaps have already gained ubiquity worldwide, others could act as if they were persistent, simply because their continual infusion into the aquatic environment serves to sustain perpetual life-cycle exposures for aquatic organisms. This review attempts to synthesize the literature on environmental origin, distribution/occurrence, and effects and to catalyze a more focused discussion in the environmental science community.

Pharmaceuticals and personal care products in the environment: agents of subtle change?

Tetracyclines pour le traitement des accidents cérebrovasculaires

L'invention concerne des methodes et des composes servant a traiter des maladies au moyen de composes de tetracycline a activite therapeutique cible.

Composes de tetracycline a activites therapeutiques cibles

L'invention concerne des techniques et des compositions representant un progres dans la lutte contre la resistance microbienne a l'action des medicaments. On a decouvert des pompes d'ecoulement de type AcrAB pour lutter contre la resistance a l'action des medicaments, meme dans le cas de microbes tres resistants. L'invention concerne egalement des techniques de traitement d'infection, des techniques de criblage d'inhibiteurs de pompes d'ecoulement de type AcrAB, et des techniques permettant d'ameliorer l'activite antimicrobienne des medicaments. L'invention concerne, en outre, une composition pharmaceutique comprenant un inhibiteur de pompe d'ecoulement de type AcrAB, ainsi qu'un agent antimicrobien.

Procedes permettant de reduire la resistance microbienne a l'action des medicaments

As we go about our everyday activities, we are continually interacting with free-living, single-cell microorganisms invisible to the naked eye. In 1674, a Dutch dry goods merchant, Anton van Leeuwenhoeck, first viewed tiny creatures, “wee animalcules,” moving under his hand-sized, homemade microscope. He reported and described his novel findings in letters and drawings, which he sent in 1676 to the Royal Society of London. His discovery opened our eyes and our minds to the existence of living matter that could not normally be seen by the eye. These microscopic beings made up an exotic, previously unimagined world that shared our environment.

The Disease and the Cure

The instant methods and compositions represent an advance in controlling drug resistance in microbes. AcrAB-like efflux pumps have been found to control resistance to drugs, even in highly resistant microbes. Accordingly, methods of treating infection, methods of screening for inhibitors of AcrAB-like efflux pumps, and methods of enhancing antimicrobial activity of drugs are provided. Pharmaceutical composition comprising an inhibitor of an AcrAB-like efflux pump and an antimicrobial agent are also provided.

Stuart B. Levy

Papers

Tetracyclines pour le traitement des accidents cérebrovasculaires

Composes de tetracycline a activites therapeutiques cibles

Procedes permettant de reduire la resistance microbienne a l'action des medicaments

The Disease and the Cure

Compositions an inhibitor of an accrab-like efflux pump for reducung microbial resistance to drugs