Scott J. Hultgren

Bio: Scott J. Hultgren is an academic researcher from Washington University in St. Louis. The author has contributed to research in topics: Pilus & Bacterial adhesin. The author has an hindex of 109, co-authored 380 publications receiving 38674 citations. Previous affiliations of Scott J. Hultgren include University College London & Vrije Universiteit Brussel.

Urinary tract infections: epidemiology, mechanisms of infection and treatment options

Abstract: Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.

Role of Escherichia coli Curli Operons in Directing Amyloid Fiber Formation

Abstract: Amyloid is associated with debilitating human ailments including Alzheimer's and prion diseases. Biochemical, biophysical, and imaging analyses revealed that fibers produced by Escherichia coli called curli were amyloid. The CsgA curlin subunit, purified in the absence of the CsgB nucleator, adopted a soluble, unstructured form that upon prolonged incubation assembled into fibers that were indistinguishable from curli. In vivo, curli biogenesis was dependent on the nucleation-precipitation machinery requiring the CsgE and CsgF chaperone-like and nucleator proteins, respectively. Unlike eukaryotic amyloid formation, curli biogenesis is a productive pathway requiring a specific assembly machinery.

Regulation of Intestinal α-Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense

Abstract: Precursors of α-defensin peptides require activation for bactericidal activity. In mouse small intestine, matrilysin colocalized with α-defensins (cryptdins) in Paneth cell granules, and in vitro it cleaved the pro segment from cryptdin precursors. Matrilysin-deficient (MAT−/−) mice lacked mature cryptdins and accumulated precursor molecules. Intestinal peptide preparations from MAT−/− mice had decreased antimicrobial activity. Orally administered bacteria survived in greater numbers and were more virulent in MAT−/− mice than in MAT+/+ mice. Thus, matrilysin functions in intestinal mucosal defense by regulating the activity of defensins, which may be a common role for this metalloproteinase in its numerous epithelial sites of expression.

Intracellular bacterial biofilm-like pods in urinary tract infections

Abstract: Escherichia coli entry into the bladder is met with potent innate defenses, including neutrophil influx and epithelial exfoliation. Bacterial subversion of innate responses involves invasion into bladder superficial cells. We discovered that the intracellular bacteria matured into biofilms, creating pod-like bulges on the bladder surface. Pods contained bacteria encased in a polysaccharide-rich matrix surrounded by a protective shell of uroplakin. Within the biofilm, bacterial structures interacted extensively with the surrounding matrix, and biofilm associated factors had regional variation in expression. The discovery of intracellular biofilm-like pods explains how bladder infections can persist in the face of robust host defenses.

Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli.

Abstract: Virtually all uropathogenic strains of Escherichia coli encode filamentous surface adhesive organelles called type 1 pili. High-resolution electron microscopy of infected mouse bladders revealed that type 1 pilus tips interacted directly with the lumenal surface of the bladder, which is embedded with hexagonal arrays of integral membrane glycoproteins known as uroplakins. Attached pili were shortened and facilitated intimate contact of the bacteria with the uroplakin-coated host cells. Bacterial attachment resulted in exfoliation of host bladder epithelial cells as part of an innate host defense system. Exfoliation occurred through a rapid apoptosis-like mechanism involving caspase activation and host DNA fragmentation. Bacteria resisted clearance in the face of host defenses within the bladder by invading into the epithelium.

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

Abstract: 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。

Antimicrobial peptides of multicellular organisms

Abstract: 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?

Protein Misfolding, Functional Amyloid, and Human Disease

Abstract: 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.

Pathogenic Escherichia coli

Abstract: 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.