Neutrophil Extracellular Traps in Infectious Human Diseases

Neutrophils, as the main cells of the first line of host defense against microbial pathogens, are responsible for pathogen recognition, inhibition of pathogen spreading into the host tissue, and finally, killing the invader cells. Neutrophils carry out these functions via numerous mechanisms, including a relatively recently described activity based on a release of neutrophil extracellular traps (NETs), a process called netosis. NETs are structures composed of DNA backbone, decorated with antimicrobial factors, derived from neutrophil granules. The structure of NETs and their enzymatic and microbicidal inclusions enable efficient trapping and killing of microorganisms within the neutrophil extracellular space. However, the efficiency of NETs depends on neutrophil ability to recognize pathogen signals and to trigger rapid responses. In this chapter, we focus on possible pathways involved in the release of NETs and summarize the current knowledge on triggers of this process during bacterial, fungal, protozoan, and viral infections. We also consider the mechanisms used by microorganisms to evade NET-killing activity and analyze the harmful potential of NETs against the host cells and the contribution of NETs to noninfectious human diseases

The upregulation of thiamine (vitamin B1) biosynthesis in Arabidopsis thaliana seedlings under salt and osmotic stress conditions is mediated by abscisic acid at the early stages of this stress response

<p>Abstract</p> <p>Background</p> <p>Recent reports suggest that vitamin B₁(thiamine) participates in the processes underlying plant adaptations to certain types of abiotic and biotic stress, mainly oxidative stress. Most of the genes coding for enzymes involved in thiamine biosynthesis in <it>Arabidopsis thaliana </it>have been identified. In our present study, we examined the expression of thiamine biosynthetic genes, of genes encoding thiamine diphosphate-dependent enzymes and the levels of thiamine compounds during the early (sensing) and late (adaptation) responses of Arabidopsis seedlings to oxidative, salinity and osmotic stress. The possible roles of plant hormones in the regulation of the thiamine contribution to stress responses were also explored.</p> <p>Results</p> <p>The expression of Arabidopsis genes involved in the thiamine diphosphate biosynthesis pathway, including that of <it>THI1</it>, <it>THIC</it>, <it>TH1 </it>and <it>TPK</it>, was analyzed for 48 h in seedlings subjected to NaCl or sorbitol treatment. These genes were found to be predominantly up-regulated in the early phase (2-6 h) of the stress response. The changes in these gene transcript levels were further found to correlate with increases in thiamine and its diphosphate ester content in seedlings, as well as with the enhancement of gene expression for enzymes which require thiamine diphosphate as a cofactor, mainly α-ketoglutarate dehydrogenase, pyruvate dehydrogenase and transketolase. In the case of the phytohormones including the salicylic, jasmonic and abscisic acids which are known to be involved in plant stress responses, only abscisic acid was found to significantly influence the expression of thiamine biosynthetic genes, the thiamine diphosphate levels, as well as the expression of genes coding for main thiamine diphosphate-dependent enzymes. Using Arabidopsis mutant plants defective in abscisic acid production, we demonstrate that this phytohormone is important in the regulation of <it>THI1 </it>and <it>THIC </it>gene expression during salt stress but that the regulatory mechanisms underlying the osmotic stress response are more complex.</p> <p>Conclusions</p> <p>On the basis of the obtained results and earlier reported data, a general model is proposed for the involvement of the biosynthesis of thiamine compounds and thiamine diphosphate-dependent enzymes in abiotic stress sensing and adaptation processes in plants. A possible regulatory role of abscisic acid in the stress sensing phase is also suggested by these data.</p

Extracellular aspartic protease SAP2 of Candida albicans yeast cleaves human kininogens and releases proinflammatory peptides, Met-Lys-bradykinin and des-Arg(9)-Met-Lys-bradykinin

Bradykinin-related peptides, universal mediators of inflammation collectively referred to as the kinins, are often produced in excessive amounts during microbial infections. We have recently shown that the yeast Candida albicans, the major fungal pathogen to humans, can exploit two mechanisms to enhance kinin levels at the sites of candidial infection, one depending on adsorption and activation of the endogenous kinin-generating system of the host on the fungal cell wall and the other relying on cleavage of kinin precursors, the kininogens, by pathogen-secreted proteases. This work aimed at assigning this kininogenase activity to the major secreted aspartic protease of C. albicans (SAP2). The purified SAP2 was shown to cleave human kininogens, preferably the low molecular mass form (LK) and optimally in an acidic environment (pH 3.5-4.0), and to produce two kinins, Met-Lys-bradykinin and its derivative, {[}Hydroxyproline(3)]-Met-Lys-bradykinin, both of which are capable of interacting with cellular bradykinin receptors of the B2 subtype. Additionally, albeit with a lower yield, des-Arg(9)-Met-Lys-bradykinin, an effective agonist of B1-subtype receptors, was released. The pathophysiological potential of these kinins and des-Arg-kinin was also proven by presenting their ability to stimulate human promonocytic cells U937 to release proinflammatory interleukin 1 beta (IL-1 beta) and IL-6

Interactions of Candida albicans Cells with Aerobic and Anaerobic Bacteria during Formation of Mixed Biofilms in the Oral Cavity

Biofilm is a compact coating formed on various artificial and physiologic surfaces by a population of microorganisms which in this habitat establish a close cooperation, exploiting both the physical interactions that stabilize the community and chemical cooperation, engaging numerous agents to modify the environment, i.e., to influence the acidity, nutrient acquisition, or oxygen availability. Microorganisms can also communicate using quorum-sensing molecules carrying specific messages. Some microbes temporarily dominate, while others are constantly replaced by different community members. But these co-operations or competitions have a deep sense—they serve to protect the whole community against the defense system of the host to assure survival. The oral cavity is inhabited by diverse microorganisms, including bacteria, but also yeast-like fungi from the genus Candida that stay under a tight control of the host as long as its immune system is not weakened; then these relatively mild commensals convert to dangerous pathogens that start the invasion often in collaboration with other microbes. Elongated hyphal forms of fungal cells favor the biofilm type of growth and communication with other microbes supporting immune resistance of the biofilm. In this chapter, we discuss the mechanisms of interactions between bacteria and C. albicans in the oral cavity, their communication, host responses, and possible strategies of anti-biofilm treatment

Adhesive protein-mediated crosstalk between <i>Candida albicans</i> and <i>Porphyromonas gingivalis</i> in dual species biofilm protects the anaerobic bacterium in unfavorable oxic environment

Abstract The oral cavity contains different types of microbial species that colonize human host via extensive cell-to-cell interactions and biofilm formation. Candida albicans —a yeast-like fungus that inhabits mucosal surfaces—is also a significant colonizer of subgingival sites in patients with chronic periodontitis. It is notable however that one of the main infectious agents that causes periodontal disease is an anaerobic bacterium— Porphyromonas gingivalis. In our study, we evaluated the different strategies of both pathogens in the mutual colonization of an artificial surface and confirmed that a protective environment existed for P. gingivalis within developed fungal biofilm formed under oxic conditions where fungal cells grow mainly in their filamentous form i.e. hyphae. A direct physical contact between fungi and P. gingivalis was initiated via a modulation of gene expression for the major fungal cell surface adhesin Als3 and the aspartic proteases Sap6 and Sap9. Proteomic identification of the fungal surfaceome suggested also an involvement of the Mp65 adhesin and a “moonlighting” protein, enolase, as partners for the interaction with P. gingivalis. Using mutant strains of these bacteria that are defective in the production of the gingipains—the proteolytic enzymes that also harbor hemagglutinin domains—significant roles of these proteins in the formation of bacteria-protecting biofilm were clearly demonstrated

Modulation of thiamine metabolism in Zea mays seedlings under conditions of abiotic stress

of abiotic stres