Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens

Proceedings of the National Academy of Sciences, Год журнала: 2013, Номер 110(10), С. 3841 - 3846

Опубликована: Фев. 19, 2013

The S100A8/S100A9 heterodimer calprotectin (CP) functions in the host response to pathogens through a mechanism termed "nutritional immunity." CP binds Mn(2+) and Zn(2+) with high affinity starves bacteria of these essential nutrients. Combining biophysical, structural, microbiological analysis, we identified molecular basis sequestration. asymmetry creates single Mn(2+)-binding site from six histidine residues, which distinguishes all other proteins. Analysis mutants altered metal-binding properties revealed that, despite both being metals, maximal growth inhibition multiple bacterial requires These data establish importance sequestration defense against infection, explain broad-spectrum antimicrobial activity relative S100 proteins, clarify impact metal depletion on innate immune infection.

Язык: Английский

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Tryptophan Biosynthesis Protects Mycobacteria from CD4 T-Cell-Mediated Killing

Cell, Год журнала: 2013, Номер 155(6), С. 1296 - 1308

Опубликована: Дек. 1, 2013

Язык: Английский

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Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence

Frontiers in Cellular and Infection Microbiology, Год журнала: 2013, Номер 3

Опубликована: Янв. 1, 2013

For all microorganisms, acquisition of metal ions is essential for survival in the environment or their infected host. Metal are required many biological processes as components metalloproteins and serve cofactors structural elements enzymes. However, it critical bacteria to ensure that uptake availability accordance with physiological needs, an imbalance bacterial homeostasis deleterious. Indeed, host defense strategies against infection either consist starvation by sequestration toxicity highly concentrated release metals. To overcome these strategies, employ a variety export systems finely regulate numerous transcriptional regulators, allowing them adapt changing environmental conditions. As consequence, iron, zinc, manganese copper significantly contribute virulence pathogenic bacteria. during course our experiments on role iron transporters extraintestinal Escherichia coli (ExPEC) virulence, we observed depending strain tested, importance tested may be different. This could due different set present strains, but literature also suggests each pathogen must particular microenvironment its site infection, system can differ from another. In this review, involved transport Enterobacteria main regulators responsible controlled expression. We discuss relative tissues they infect.

Язык: Английский

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Proteus mirabilisand Urinary Tract Infections

Microbiology Spectrum, Год журнала: 2015, Номер 3(5)

Опубликована: Сен. 4, 2015

ABSTRACT Proteus mirabilis is a Gram-negative bacterium and well known for its ability to robustly swarm across surfaces in striking bulls’-eye pattern. Clinically, this organism most frequently pathogen of the urinary tract, particularly patients undergoing long-term catheterization. This review covers P. with focus on tract infections (UTI), including disease models, vaccine development efforts, clinical perspectives. Flagella-mediated motility, both swimming swarming, central facet organism. The regulation complex process contribution virulence discussed, along type VI-secretion system-dependent intra-strain competition, which occurs during swarming. uses diverse set factors access colonize host urease stone formation, fimbriae other adhesins, iron zinc acquisition, proteases toxins, biofilm pathogenesis. While significant advances field have been made, challenges remain combatting complicated UTI deciphering

Язык: Английский

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Iron at the interface of immunity and infection

Frontiers in Pharmacology, Год журнала: 2014, Номер 5

Опубликована: Июль 16, 2014

Both, mammalian cells and microbes have an essential need for iron, which is required many metabolic processes microbial pathogenicity. In addition, cross-regulatory interactions between iron homeostasis immune function are evident. Cytokines the acute phase protein hepcidin affect leading to retention of metal within macrophages hypoferremia. This considered result from a defense mechanism body limit availability extracellular pathogens while on other hand reduction circulating results in development anemia inflammation. Opposite, erythropoiesis inducing hormone erythropoietin innate responses by influencing interferon-gamma (IFN-γ) mediated (iron) or NF-kB inducible (erythropoietin) effector pathways macrophages. Thus, loaded with lose their ability kill intracellular via IFN-γ such as nitric oxide (NO) formation. Accordingly, invaded bacterium Salmonella enterica serovar Typhimurium increase expression export ferroportin thereby reducing intramacrophage bacteria side strengthening anti-microbial macrophage increased formation NO TNF-α. certain resistance genes natural associated (Nramp1) lipocalin-2 exert part antimicrobial activity controlling host and/or homeostasis. Consequently, pharmacological dietary modification cellular trafficking enhances but may susceptibility compartment vice versa. control over central battlefield host-pathogen interplay course infectious disease favor either pathogenic invader.

Язык: Английский

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