Interplay between iron homeostasis and virulence: Fur and RyhB as major regulators of bacterial pathogenicity

Author: Porcheron, Gaelle; Dozois, Charles M. Description: In bacteria-host interactions, competition for iron is critical for the outcome of the infection. As a result of its redox properties, this metal is essential for the growth and proliferation of most living organisms, including pathogenic bacteria. This metal is also potentially toxic, making the precise maintenance of iron homeostasis necessary for survival. Iron acquisition and storage control is mediated in most bacteria by the global ferric uptake regulator (Fur) and iron-responsive small regulatory non-coding RNAs (RyhB in the model organism Escherichia coli)….

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Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease

Author: Kumar, D.K.V.; Choi, S.H.; Washicosky, K.J.; Eimer, W.A.; Tucker, S.; Ghofrani, J.; Lefkowitz, A.; McColl, G.; Goldstein, L.E.; Tanzi, R.E.; Moir, R.D. Description: The amyloid-beta peptide (AB) is a key protein in Alzheimer’s disease (AD) pathology. We previously reported in vitro evidence suggesting that AB is an antimicrobial peptide. We present in vivo data showing that AB expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. We show that AB oligomerization, a behavior traditionally viewed as intrinsically pathological, may be necessary for…

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

Author: Flores-Mireles, A.L.; Walker, J.N.; Caparon, M.; Hultgren, S.J. Description: 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…

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Molecular mechanisms of antibiotic resistance

Author: Blair, J.M.A.; Webber, M.A.; Baylay, A.J.; Ogbolu, D.O.; Piddock, L.J.V. Description: Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including…

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The Bacteroides fragilis pathogenicity island links virulence and strain competition

Author: Casterline, Benjamin W.; Hecht, Aaron L.; Choi, Vivian M.; Bubeck Wardenburg, Juliane Description: The mature microbiome is a stable ecosystem that resists perturbation despite constant host exposure to exogenous microbes. However, the microbial mechanisms determining microbiome development and composition are poorly understood. We recently demonstrated that a non-toxigenic B. fragilis (NTBF) strain restricts enteric colonization by an enterotoxigenic (ETBF) strain dependent on a type VI secretion system (T6SS). We show here that a second enterotoxigenic strain is competent to colonize, dependent on the Bacteroides fragilis pathogenicity island (BFPAI). Additional…

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Epidemiology and pathogenesis of Bacillus cereus infections

Author: Kotiranta, A.; Lounatmaa, K.; Haapasalo, M. Description: Bacillus cereus is a causative agent in both gastrointestinal and in nongastrointestinal infections. Enterotoxins, emetic toxin (cereulide), hemolysins, and phoshpolipase C as well as many enzymes such as beta-lactamases, proteases and collagenases are known as potential virulence factors of B. cereus. A special surface structure of B. cereus cells, the S-layer, has a significant role in the adhesion to host cells, in phagocytosis and in increased radiation resistance. Interest in B. cereus has been growing lately because it seems that B. cereus-related…

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The roles of biofilm matrix polysaccharide Psl in mucoid Pseudomonas aeruginosa biofilms

Author: Ma, L.; Wang, S.; Wang, D.; Parsek, M.R.; Wozniak, D.J. Description: The opportunistic pathogen Pseudomonas aeruginosa causes life-threatening, persistent infections in patients with cystic fibrosis (CF). Persistence is attributed to the ability of these bacteria to form structured communities (biofilms). Biofilms rely on an extracellular polymeric substances matrix to maintain structure. Psl exopolysaccharide is a key matrix component of nonmucoid biofilms, yet the role of Psl in mucoid biofilms is unknown. In this report, using a variety of mutants in a mucoid P. aeruginosa background, we found that deletion…

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Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection

Author: Wheeler, Kelsey M.; Carcamo-Oyarce, Gerardo; Turner, Bradley S.; Dellos-Nolan, Sheri; Co, Julia Y.; Lehoux, Sylvain; Cummings, Richard D.; Wozniak, Daniel J.; Ribbeck, Katharina Description: A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts. Mucus forms the first line of defence while housing trillions of microorganisms that constitute the microbiota. Rarely do these microorganisms cause infections in healthy mucus, suggesting that mechanisms exist in the mucus layer that regulate virulence. Using the bacterium Pseudomonas aeruginosa and a…

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Copper and Antibiotics: Discovery, Modes of Action, and Opportunities for Medicinal Applications

Author: Dalecki, Alex G.; Crawford, Cameron L.; Wolschendorf, Frank Description: Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects. This weakness is actively exploited by phagocytes,…

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Pathogenic Escherichia coli

Author: Kaper, James B.; Nataro, James P.; Mobley, Harry L. Description: 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…

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