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?

Methods: Deletion mutants, an acrABp-lacZ fusion and reverse transcription – real-time quantitative PCR experiments were used to study the role of AcrAB-TolC and metabolism in regulating gene expression of the acrAB operon and its transcriptional regulators. Results: Deletion of the acrB gene increased the expression of the acrAB operon. A similar induction of acrAB was found whenacrA ortolC was deleted, and when the pump function was inhibited using phenylalanine-arginine-bnaphthylamide. The induction ofacrAB in theDacrB strain was totally (AcrR or SoxS) or partially (SoxR or MarA) prevented when the genes for these acrAB regulators were also deleted. The expression of soxS and marA, but not of acrR, was increased in the DacrB strain, which also showed altered expression of many other genes related to different cellular processes, including motility. Deletion of the metabolic genes entA and entE (enterobactin biosysnthesis), glpX (gluconeogenesis), cysH (cysteine biosynthesis) and purA (purine biosynthesis) also prevented activation of the acrAB promoter in the DacrB strain. Addition of the enterobactin biosynthesis intermediate metabolite 2,3-dihydroxybenzoate induced the expression of acrAB. Conclusions: These results together suggest a model in which the AcrAB-TolC pump effluxes cellular metabolites that are toxic and/or have a signalling role. If the pump is inactivated or inhibited, these metabolites would accumulate, inactivating AcrR and/or up-regulating soxS and marA expression, ultimately triggering the up-regulation of acrAB expression to restore homeostasis.

Regulation of acrAB expression by cellular metabolites in Escherichia coli

The possible association between triclosan and bacterial susceptibility to antibiotic was examined among staphylococci and several species of gram-negative bacteria (GNB) isolated from the hands of individuals in a community setting. Hand cultures from individuals randomized to using either antibacterial cleaning and hygiene products (including a hand soap containing 0.2% triclosan) or nonantibacterial cleaning and hygiene products for a 1-year period were taken at baseline and at the end of the year. Although there was no statistically significant association between triclosan MICs and susceptibility to antibiotic, there was an increasing trend in the association the odds ratios (ORs) for all species were compared at baseline (OR = 0.65, 95% confidence interval [95%CI] = 0.33 to 1.27) versus at the end of the year (OR = 1.08, 95%CI = 0.62 to 1.97) and for GNB alone at baseline(OR = 0.66, 95%CI = 0.29 to 1.51) versus the end of year (OR = 2.69, 95%CI = 0.78 to 9.23) regardless of the hand-washing product used. Moreover, triclosan MICs were higher in some of the species compared to earlier reports on household, clinical, and industrial isolates, and some of these isolates had triclosan MICs in the range of concentrations used in consumer products. The absence of a statistically significant association between elevated triclosan MICs and reduced antibiotic susceptibility may indicate that such a correlation does not exist or that it is relatively small among the isolates that were studied. Still, a relationship may emerge after longer-term or higher-dose exposure of bacteria to triclosan in the community setting.

/pdf/relationship-between-triclosan-and-susceptibilities-of-4ye27je3o4.pdf

Relationship between Triclosan and Susceptibilities of Bacteria Isolated from Hands in the Community

When cells of Escherichia coli are exposed briefly to ethylenediaminetetraacetate (EDTA), they release approximately half their lipopolysaccharide (LPS).1, 2 The amount lost for a given strain appears fixed, since it cannot be increased by several changes in procedure, including increase in the time of exposure and concentration of EDTA.2 Because these results suggested that the released LPS might differ from the remainder, the metabolic relationship between these two fractions was investigated. Lipopolysaccharide was labeled with galactose-C'4 for various periods of time, using a mutant that can incorporate this sugar into only LPS, and the amount of labeled LPS released by EDTA treatment was determined. The results show that in the growing cell the fraction of LPS that is released by EDTA is in rapid equilibrium with that which is retained. Newly synthesized LPS is initially part of the retained fraction but rapidly enters this equilibrium. Materials and Method&.E. coli J5, a mutant derived from E. coli 0111:B4, was used. This mutant lacks UDP-galactose-4-epimerase and cannot form complete LPS without galactose in its growth medium; with galactose, it forms a cell wall having the same structure as that of its parent.' This organism was the gift of Dr. Edward Heath. Cells were grown to mid-exponential phase (5 X 108 cells/ml) in Trypticase soy broth containing 0.25% galactose and 0.25%o glucose. Where indicated, LPS was labeled with galactose-1-C\"4 (New England Nuclear Corporation). When labeled cells were diluted into nonradioactive medium and grown for various lengths of time, there was no loss of galactose label from TCA-precipitable material. EDTA treatment was performed as previously described,l 2 except that cells were washed with 0.85% NaCl at 40 before treatment; exposure to EDTA (2-6 X 10-4 M) was terminated after 4-6 min by addition of MgCl2 (2-6 X 10-3 M), and the cells were centrifuged. The amount of LPS in the supernatant and cell-pellet fractions was estimated by assaying for colitose as previously described.'1 4 This sugar is present only in LPS and its precursors,5 and its per cent release by EDTA in the parent strain is the same as that of total cell LPS.2 The amount of labeled galactose in LPS was estimated by precipitating aliquots of the supernatant and cell-pellet material with 5% trichloroacetic acid (TCA) at 40, filtering on Millipore filters (pore size 0.22 JA), washing once with 2.0 ml cold 5% TCA and three times with 5.0 ml water, and measuring the radioactivity in a scintillation counter as previously described.' In mutants of Salmonella lacking UDP-galactose-4-epimerase, virtually all acidprecipitable galactose is in LPS.6 The same is true for this E. coli mutant as shown by the following control experiments: (1) Cells labeled for 2 min and for 3 hr (four generations) were extracted with phenol and the LPS was purified as previously described.2 In several experiments 65-100% of the original TCA-precipitable counts were recovered in the purified LPS with no systematic differences between the 2-min and the 3-hr sample. For both times of labeling, the ratio of TCA-precipitable galactose-C14 to total colitose in the cells was the same as the ratio of total galactose-C'4 to colitose in the purified LPS. (2) When fully labeled cells were treated with EDTA, the ratio of colitose to TCA-precipitable galactose-C'4 was the same for the whole cell, the released material, and the material retained in the cells. (3) Highly labeled galactose-1-C'4 and UDP-galactose-C'4

An equilibrium between two fractions of lipopolysaccharide in Escherichia coli.

Commensals upon us.

The division of labour is a central feature of the most sophisticated biological systems, including genomes, multicellular organisms and societies, which took millions of years to evolve. Here we show that a well-organized and robust division of labour can evolve in a matter of days. Mutants emerge within bacterial colonies and work with the parent strain to gain new territory. The two strains self-organize in space: one provides a wetting polymer at the colony edge, whereas the other sits behind and pushes them both along. The emergence of the interaction is repeatable, bidirectional and only requires a single mutation to alter production of the intracellular messenger, cyclic-di-GMP. Our work demonstrates the power of the division of labour to rapidly solve biological problems without the need for long-term evolution or derived sociality. We predict that the division of labour will evolve frequently in microbial populations, where rapid genetic diversification is common.

Stuart B. Levy

Papers

Regulation of acrAB expression by cellular metabolites in Escherichia coli

Relationship between Triclosan and Susceptibilities of Bacteria Isolated from Hands in the Community

An equilibrium between two fractions of lipopolysaccharide in Escherichia coli.

Commensals upon us.

Rapid radiation in bacteria leads to a division of labour.