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

J. Appl. Cryst.の発刊に際して

Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

/pdf/antimicrobial-peptides-of-multicellular-organisms-24vvoqtunk.pdf

Antimicrobial peptides of multicellular organisms

Peptides or proteins convert under some conditions from their soluble forms into highly ordered fibrillar aggregates. Such transitions can give rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we identify the diseases known to be associated with formation of fibrillar aggregates and the specific peptides and proteins involved in each case. We describe, in addition, that living organisms can take advantage of the inherent ability of proteins to form such structures to generate novel and diverse biological functions. We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level. Finally, we discuss the relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate and describe some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior.

/pdf/protein-misfolding-functional-amyloid-and-human-disease-2w386pwb7k.pdf

Protein Misfolding, Functional Amyloid, and Human Disease

Few microorganisms are as versatile as Escherichia coli. An important member of the normal intestinal microflora of humans and other mammals, E. coli has also been widely exploited as a cloning host in recombinant DNA technology. But E. coli is more than just a laboratory workhorse or harmless intestinal inhabitant; it can also be a highly versatile, and frequently deadly, pathogen. Several different E. coli strains cause diverse intestinal and extraintestinal diseases by means of virulence factors that affect a wide range of cellular processes.

Pathogenic Escherichia coli

The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

COMPOSITIONS AND METHODS FOR THE TREATMENT AND PREVENTION OF Ebp PILUS-RELATED DISEASES

Many species of gram-negative bacteria employ a conserved protein secretion system termed the chaperone-usher pathway to assemble a diverse array of multisubunit protein fibers on their surfaces Fibers assembled by the chaperone-usher pathway play critical roles in bacterially mediated disease: they mediate bacterial attachment to host tissues, often an essential early step in pathogenesis; they facilitate the evasion of host defenses; and they promote biofilm formation, a contributing factor both to the establishment of infection and to bacterial resistance to antibiotic treatment Fibers assembled by the chaperone-usher pathway are typically encoded in individual gene clusters The well-studied surface organelles, the capsular F1 antigen of Yersinia pestis and the hemagglutinating pilus of the human respiratory pathogen Haemophilus influenzae, highlight the structural diversity of fibers assembled by the chaperone-usher pathway The periplasmic chaperones of the chaperone-usher pathway share conserved structural features first revealed in the crystal structure of PapD Each chaperone consists of two domains that are oriented at an approximate right angle to each other to produce an L-shaped molecule Donor strand exchange occurs very rapidly in vivo but only relatively slowly and inefficiently in vitro in the absence of the usher This suggests that while the chaperone primes the subunit for donor strand exchange, additional interactions with the usher may facilitate subunit uncapping during fiber formation The relative specificity of donor strand exchange determines, at least in part, the function of individual subunits and their order of incorporation into the fiber

The Chaperone-Usher Pathway of Pilus Fiber Biogenesis

Receptor Binding Studies Disclose a Novel Class of High-Affinity Inhibitors of the Escherichia coli FimH Adhesin

Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify nearest known references and find variants for multiple conspecific strains within a sample at relative abundances below 0.1% in typical metagenomic datasets.

https://www.biorxiv.org/content/biorxiv/early/2021/02/14/2021.02.14.431013.full.pdf

Scott J. Hultgren

Papers

COMPOSITIONS AND METHODS FOR THE TREATMENT AND PREVENTION OF Ebp PILUS-RELATED DISEASES

The Chaperone-Usher Pathway of Pilus Fiber Biogenesis

Receptor Binding Studies Disclose a Novel Class of High-Affinity Inhibitors of the Escherichia coli FimH Adhesin

StrainGE: A toolkit to track and characterize low-abundance strains in complex microbial communities

Crystal Structure of the Periplasmic Chaperone SfaE