ABSTRACT
Neutrophils phagocytose and kill microbes upon phagolysosomal fusion. Recently we found that activated neutrophils form extracellular fibres that consist of granule proteins and chromatin. These neutrophil extracellular traps (NETs) degrade virulence factors and kill Gram positive and negative bacteria. Here we show for the first time that Candida albicans, a eukaryotic pathogen, induces NET-formation and is susceptible to NET-mediated killing. C. albicans is the predominant aetiologic agent of fungal infections in humans, particularly in immunocompromised hosts. One major virulence trait of C. albicans is its ability to reversibly switch from singular budding cells to filamentous hyphae. We demonstrate that NETs kill both yeast-form and hyphal cells, and that granule components mediate fungal killing. Taken together our data indicate that neutrophils trap and kill ascomycetous yeasts by forming NETs.
Subject(s)
Candida albicans/physiology , Hyphae/physiology , Neutrophils/immunology , Phagocytosis , Histones/physiology , Humans , In Vitro Techniques , Microbial Viability , Neutrophil ActivationABSTRACT
Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
Subject(s)
Immunity, Innate , Neutrophil Activation , Neutrophils/immunology , Salmonella typhimurium/physiology , Shigella flexneri/physiology , Staphylococcus aureus/physiology , Animals , Appendicitis/immunology , Bacterial Proteins/metabolism , Blood Bactericidal Activity , Cytochalasin D/pharmacology , Cytoplasmic Granules/metabolism , DNA/analysis , DNA/metabolism , Dysentery, Bacillary/immunology , Endopeptidases/metabolism , Histones/analysis , Histones/metabolism , Humans , Leukocyte Elastase/analysis , Leukocyte Elastase/metabolism , Microscopy, Electron , Neutrophils/chemistry , Neutrophils/physiology , Neutrophils/ultrastructure , Phagocytosis , Rabbits , Salmonella typhimurium/immunology , Shigella flexneri/immunology , Staphylococcus aureus/immunology , Virulence Factors/metabolismABSTRACT
Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.
Subject(s)
Emigration and Immigration , Genetics, Population , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Polymorphism, Genetic , Africa , Agriculture , Americas , Asia , Bacterial Proteins/genetics , Bayes Theorem , Ethnicity , Europe , Genes, Bacterial , Genetic Variation , Geography , Helicobacter Infections/transmission , Helicobacter pylori/classification , Helicobacter pylori/isolation & purification , Humans , Indians, North American , Language , Polynesia , Racial Groups , Recombination, Genetic , Social Problems , SoftwareABSTRACT
A global collection of 26 isolates of Salmonella typhi was investigated by sequencing a total of 3336 bp in seven housekeeping genes. Only three polymorphic sites were found and the isolates fell into four sequence types. These results show that S. typhi is a recent clone whose last common ancestor existed so recently that multiple mutations have not yet accumulated. Based on molecular clock rates for the accumulation of synonymous polymorphisms, we estimate that the last common ancestor of S. typhi existed 15,000-150,000 years ago, during the human hunter-gatherer phase and prior to the development of agriculture and the domestication of animals.
