Lactoferrin, a multifunctional iron binding glycoprotein, plays an important role in immune regulation and defence mechanisms against bacteria, fungi and viruses. Lactoferrin’s iron withholding ability is related to inhibition of microbial growth as well as to modulation of motility, aggregation and biofilm formation of pathogenic bacteria. Independently of iron binding capability, lactoferrin interacts with microbial, viral and cell surfaces thus inhibiting microbial and viral adhesion and entry into host cells. Lactoferrin can be considered not only a primary defense factor against mucosal infections, but also a polyvalent regulator which interacts in viral infectious processes. Its antiviral activity, demonstrated against both enveloped and naked viruses, lies in the early phase of infection, thus preventing entry of virus in the host cell. This activity is exerted by binding to heparan sulphate glycosaminoglycan cell receptors, or viral particles or both. Despite the antiviral effect of lactoferrin, widely demonstrated in vitro studies, few clinical trials have been carried out and the related mechanism of action is still under debate. The nuclear localization of lactoferrin in different epithelial human cells suggests that lactoferrin exerts its antiviral effect not only in the early phase of surface interaction virus-cell, but also intracellularly. The capability of lactoferrin to exert a potent antiviral activity, through its binding to host cells and/or viral particles, and its nuclear localization strengthens the idea that lactoferrin is an important brick in the mucosal wall, effective against viral attacks and it could be usefully applied as novel strategy for treatment of viral infections.
Aims: To analyse the environmental stimuli modulating violacein and biofilm production in Janthinobacterium lividum. Methods and Results: Violacein and biofilm production by J. lividum DSM1522T was assayed in different growth conditions. Our data suggest that violacein and biofilm production is controlled by the carbon source, being inhibited by glucose and enhanced by glycerol. J. lividum produced violacein also in the presence of different sub‐inhibitory concentrations of ampicillin. As opposite, the production of N‐acylhomoserine lactone(s), quorum sensing regulators was shown to be positively regulated by glucose. Moreover, violacein‐producing cultures of J. lividum showed higher CFU counts than violacein‐nonproducing ones. Conclusions: Taken together, our results suggest that violacein and biofilm production could be regulated by a common metabolic pathway and that violacein as well as biofilm could represent a response to environmental stresses and a key factor in the survival mechanisms of J. lividum. Significance and Impact of the Study: Although several recent studies disclosed a number of interesting biological properties of violacein, few data are reported on the physiologic function of violacein in J. lividum. This paper adds new information on the complex mechanisms allowing and regulating bacterial life in hostile environments.
Bacterial nonspecific acid phosphohydrolases (NSAPs) are secreted enzymes, produced as soluble periplasmic proteins or as membrane-bound lipoproteins, that are usually able to dephosphorylate a broad array of structurally unrelated substrates and exhibit optimal catalytic activity at acidic to neutral pH values. Bacterial NSAPs are monomeric or oligomeric proteins containing polypeptide components with an M(r) of 25-30 kDa. On the basis of amino acid sequence relatedness, three different molecular families of NSAPs can be distinguished, indicated as molecular class A, B and C, respectively. Members of each class share some common biophysical and functional features, but may also exhibit functional differences. NSAPs have been detected in several microbial taxa, and enzymes of different classes can be produced by the same bacterial species. Structural and phyletic relationships exist among the various bacterial NSAPs and some other bacterial and eucaryotic phosphohydrolases. Current knowledge on bacterial NSAPs is reviewed, together with analytical tools that may be useful for their characterization. An overview is also presented concerning the use of bacterial NSAPs in biotechnology.
Pseudomonas aeruginosa and Burkholderia cenocepacia are predominant opportunistic pathogens in cystic fibrosis (CF) patients. In healthy humans the lower respiratory tract as well as all mucosa, contains a very low free iron concentration (10-18 M), while in CF patients' sputum iron concentration is very high, showing a median value of 63x10-6 M. Accumulation of catalytic reactive iron heavily contributes to subsequent clinical complications in the lung disorders by the production of reactive oxygen species and increases bacterial growth and virulence. The data reported in this study indicate that low iron concentration (Fe 3 + 1 JA.M) induced free-living forms and motility both in P. aeruginosa and B. cenocepacia, while high iron concentrations (Fe 3 + 10 and 100 tJ.M) stimulated aggregation and biofilm formation already in the fluid phases, so demonstrating that aggregation and biofllm formation are positively iron-modulated in these bacteria. Moreover, the different morphological forms (free-living, aggregates and biofllm) showed different capabilities of adhering and invading the bronchial cell line A549. P. aeruginosa PA01 aggregates, and mostly biofllm, exerted the highest adhesion efficiency, while B. cenocepacia PV1 aggregates or biofilm the lowest. A significant reduction in invasion efficiency by P. aeruginosa biofilm and a significant increase in cell internalization by B. cenocepacia biofllm has been reported. Therefore, the iron availability is an important signal to which P. aeruginosa and B. cenocepacia counteract by leaving the motile free-living forms and entering into a new lifestyle, i.e, biofllm. These data could contribute to explain that the ironoverload of the sputum of CF patients, inducing nonmotile forms, aggregates and biofllm, may facilitate penetration of host epithelial barriers contributing to the establishment of infection, colonization, persistence and systemic spread of these opportunistic pathogens.Pseudomonas aeruginosa is a ubiquitous Gramnegative motile bacterium found in different environments such as soil, freshwater and marine habitat. Moreover, P. aeruginosa is the predominant opportunistic pathogen in cystic fibrosis (CF) patients, as the lungs of >90% of all CF patients are colonized by this bacterium (1). Chronic colonization of P. aeruginosa in CF patient airways is a major source of morbidity and mortality (2) leading to epithelial surface damage and airway plugging which results in a decrease of pulmonary function (3).Although not as prevalent as P. aeruginosa, Burkholderia cepacia is another important opportunistic respiratory pathogen in CF patients (2),
Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in “pure” M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated. The increase of IL-6 and IL-1β cytokines, following the inflammatory treatments, is associated with both upregulation of cytosolic Ftn and downregulation of Fpn, membrane-bound Cp, and transferrin receptor 1. All these changes take part into intracellular iron overload, a very unsafe condition leading in vivo to higher host susceptibility to infections as well as iron deficiency in the blood and anemia of inflammation. It is, therefore, of utmost importance to counteract the persistence of the inflammatory status to rebalance iron levels between tissues/secretions and blood. Moreover, levels of the antiinflammatory cytokine IL-10 were increased in cells treated with high doses of LPS. Conversely, IL-10 decreased when the LPS/IFN-γ mix was used, suggesting that only the inflammation triggered by LPS high doses can switch on an anti-inflammatory response in our macrophagic model. Here, we demonstrate that bLf, when included in the culture medium, significantly reduced IL-6 and IL-1β production and efficiently prevented the changes of Fpn, membrane-bound Cp, cytosolic Ftn, and transferrin receptor 1 in “pure” M1 macrophages, as well as in the more heterogeneous macrophage population. In addition, the decrease of IL-10 induced by the LPS/IFN-γ mix was counteracted by bovine lactoferrin. Several drugs capable of modulating macrophagic phenotypes are emerging as attractive molecules for treating inflammation, and in this sense, bovine lactoferrin is no exception.
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