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

http://www.klinikaikozpont.u-szeged.hu/pedia/images/pdf/CME_TEL/Full-Text/25.pdf

The Hallmarks of Aging

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

Evolution of Protein Molecules

Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.

Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance

Specific metabolite production by gut microbiota as a basis for probiotic function.

The lactic acid bacteria have evolved and been selected for exploitation in a variety of food fermentation processes The strains currently available have been subject to gene introduction and genetic reorganization by a variety of natural mechanisms The study of these mechanisms of gene transfer and DNA rearrangement has led to the development of genetic techniques that can be exploited for strain improvement These systems complement the genetic engineering methods that are described in chapter 2 This chapter covers the characterization and exploitation of conjugation, transduction and transformation in lactic acid bacteria and the exploitation of generalized recombination and chromosomal integration The lactic acid bacteria harbour a large number of transposable genetic elements and these undoubtedly contribute to the genetic instability that appears characteristic of many strains The characterization of the known IS elements and the nisin transposon are described as well as the exploitation of heterologous transposons for genetic analysis The recent development of pulsed field gel electrophoresis for analysis of whole chromosomes together with some elegant genetic strategies has led to progress in physical and genetic mapping of lactococcal genomes which is also reviewed

Gene transfer systems and transposition

The human intestinal microbiota evolves from an immature and unstable ecosystem during infancy into a more complex and stable ecosystem in adulthood. Diet is one of the main factors contributing to the composition and diversity of the human intestinal microbiota. From birth, breast milk offers the best nutritional regime for maturation of the gut, whereas the introduction of solid food selects the most adapted bacteria, converging towards an adult-like microbiota. The gut microbiota plays an important role in host health, influencing the maturation of the immune system and regulating energy metabolism. Moreover, it has become evident that the microbiota can affect brain function and behaviour. On this bidirectional communication between intestine and the central nervous system (CNS), the so called gut-brain axis, the gut influences brain development and biochemistry, whereas the brain affects gastrointestinal function. In this context, probiotics and prebiotics have been used as dietary strategies aimed at improving host health by modulating the gut ecosystem and, consequently, affecting host stress-responses, behaviour and cognition. Industrial relevance Dietary manipulation represents a strategy to preserve a healthy gastrointestinal microbial community and contribute to the well being of the host. Several food products containing probiotics and prebiotics have been developed for specific age groups such as infants and elderly, aiming to enhance the host's immune system and to prevent gastrointestinal diseases. This review presents recent strong evidence suggesting that the use of dietary approaches such as probiotics, prebiotics and diets enriched with fatty acids or proteins not only modulate the microbiota but may also impact on brain function, affecting stress-responses, behaviour and cognition. This new field of research may lead to market opportunities with the development of new dietary strategies targeting the gut–brain axis for enhanced mental health.

Gut microbiota modulation and implications for host health: Dietary strategies to influence the gut-brain axis

T. O’MAHONY, N. REKHIF, C. CAVADINI AND G.F. FITZGERALD. 2001.



Aims: The feasibility of applying variacin, a lantibiotic produced by Kocuria varians in the form of a spray-dried fermented ingredient to control the growth of psychrotrophic Bacillus cereus strains in chilled dairy foods, was evaluated.



Methods and Results: A range of chilled dairy food formulations modelling commercially-available products were fabricated, to which were added varying amounts of active ingredient. These were subsequently challenged with a B. cereus spore cocktail over a range of abuse temperatures. This work was validated by the inclusion of the fermented ingredient to commercial products.



Conclusions: Results demonstrate the functionality of the bacteriocin at refrigeration abuse temperatures, and indicate the robust nature of the proteinaceous antimicrobial agent with regard to processing.



Significance and Impact of the Study: This study indicates the applicability of fermented food ingredients containing naturally-occurring antimicrobials as additional hurdles in food preservation.

https://sfamjournals.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2672.2001.01222.x

The application of a fermented food ingredient containing 'variacin', a novel antimicrobial produced by Kocuria varians, to control the growth of Bacillus cereus in chilled dairy products.

Gerald F. Fitzgerald

Papers

Specific metabolite production by gut microbiota as a basis for probiotic function.

Gene transfer systems and transposition

Gut microbiota modulation and implications for host health: Dietary strategies to influence the gut-brain axis

The application of a fermented food ingredient containing 'variacin', a novel antimicrobial produced by Kocuria varians, to control the growth of Bacillus cereus in chilled dairy products.

Use of viability staining in combination with flow cytometry for rapid viability assessment of Lactobacillus rhamnosus GG in complex protein matrices