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Biomedical subjects

Catia Longhi

Publications and source records attributed to Catia Longhi.

5 recordsLinked to original sources

Lactoferrin inhibits early steps of human BK polyomavirus infection.

Lactoferrin, a member of the transferrin family, is a bi-globular iron binding glycoprotein, found in milk, exocrine secretions of mammals, and in secondary granules of polymorphonuclear neutrophiles that plays an important role in the defence against various pathogenic microorganisms. Previous studies in different virus-cell systems showed that lactoferrin is a potent inhibitor of different enveloped and naked virus infection. In this research we studied the effect of lactoferrin on BK polyomavirus, a human naked double-stranded DNA virus responsible for productive, persistent, and latent infections of the urinary tract. Results obtained demonstrate that lactoferrin treatment prevents early steps of BK virus infection in Vero cells, at the level of the adsorption phase, probably through the interaction with capsidic structures, although a lactoferrin-BK virus competition for cell plasma-membrane receptors cannot be ruled out.

Animals↗

Inv-mediated apoptosis of epithelial cells infected with enteropathogenic Yersinia: a protective effect of lactoferrin.

Yersinia spp., Gram-negative bacteria infecting animals and humans, contain plasmid and chromosomal genes coding for different virulence factors, of which outer membrane proteins are the most important. Among these, the inv gene product allows bacterial adherence and penetration of cells exposed at the intestinal lumen surface, and subsequent colonization of lymph nodes. In this research, we have studied the effects of bovine lactoferrin (bLf) on Y. enterocolitica and Y. pseudotuberculosis Inv-mediated interactions with epithelial cells. In particular, we analyzed bLf activity toward adhesion, invasion, and cell death induction by Yersinia spp. and the Escherichia coli HB101 (pRI203) strain (expressing the cloned Yersinia inv gene). Results showed that bLf was ineffective in bacterial adhesivity and invasivity whereas it inhibited apoptosis with a dose-dependent relationship. As epithelial cell apoptosis helps enteropathogenic Yersinia to attack the host and to gain access to the tissue, our results demonstrate a new potential antimicrobial application for bLf.

Adhesins, Bacterial↗

Lactoferrin functions: current status and perspectives.

Lactoferrin, an iron-binding glycoprotein synthesized by neutrophils and exocrine glands, plays an important role in human innate defense mechanisms against bacteria, fungi, and viruses. First, a bacteriostatic activity of lactoferrin, depending on iron withholding to bacteria, and successively a bactericidal iron-independent effect, related to its binding on bacterial surfaces, was recognized. Many other functions have been ascribed to this cationic protein, including the inhibiting action toward bacterial adhesion and invasion of target host cells. Recent research also reported the lactoferrin influence on bacterial aggregation and biofilm development of Pseudomonas aeruginosa and Streptococcus mutans. The different lactoferrin functions can be justified by different physicochemical properties of the molecule, which include the iron-binding capability, the binding to anionic cell surfaces and molecules, and serine protease activity.

Anti-Bacterial Agents↗

Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages.

Bovine lactoferrin (BLf) and its derivative peptide lactoferricin B (LfcinB) are known for their antimicrobial activity towards several pathogens, including Listeria monocytogenes, a food-borne Gram-positive invasive bacterium that infects a wide variety of host cells, including professional phagocytes. To add further information on the antibacterial effects of these compounds, the influence of BLf, LfcinB and the antimicrobial centre of LfcinB, the hexapeptide LfcinB(4-9), on the invasive behaviour of L. monocytogenes was analysed in IFN-gamma-activated human macrophagic cells (THP-1). Significant inhibition of bacterial entry in THP-1 cells was observed at LfcinB concentrations that were unable to produce any bacteriostatic or bactericidal effect, compared with BLf and LfcinB(4-9) peptide. This inhibition occurred when LfcinB was incubated during the bacterial infection step and was not due only to competition for common glycosaminoglycan receptors. Assays performed through a temperature shift from 4 to 37 degrees C showed that inhibition of invasion took place at an early post-adsorption step, although an effect on a different step of intracellular infection could not be ruled out.

Animals↗

Effect of acid adaptation on the fate of Listeria monocytogenes in THP-1 human macrophages activated by gamma interferon.

In Listeria monocytogenes the acid tolerance response (ATR) takes place through a programmed molecular response which ensures cell survival under unfavorable conditions. Much evidence links ATR with virulence, but the molecular determinants involved in the reactivity to low pHs and the behavior of acid-exposed bacteria within host cells are still poorly understood. We have investigated the effect of acid adaptation on the fate of L. monocytogenes in human macrophages. Expression of genes encoding determinants for cell invasion and intracellular survival was tested for acid-exposed bacteria, and invasive behavior in the human myelomonocytic cell line THP-1 activated with gamma interferon was assessed. Functional approaches demonstrated that preexposure to an acidic pH enhances the survival of L. monocytogenes in activated human macrophages and that this effect is associated with an altered pattern of expression of genes involved in acid resistance and cell invasion. Significantly decreased transcription of the plcA gene, encoding a phospholipase C involved in vacuolar escape and cell-to-cell spread, was observed in acid-adapted bacteria. This effect was due to a reduction in the quantity of the bicistronic plcA-prfA transcript, concomitant with an increase in the level(s) of the monocistronic prfA mRNA(s). The transcriptional shift from distal to proximal prfA promoters resulted in equal levels of the prfA transcript (and, as a consequence, of the inlA, hly, and actA transcripts) under neutral and acidic conditions. In contrast, the sodC and gad genes, encoding a cytoplasmic superoxide dismutase and the glutamate-based acid resistance system, respectively, were positively regulated at a low pH. Morphological approaches confirmed the increased intracellular survival and growth of acid-adapted L. monocytogenes cells both in vacuoles and in the cytoplasm of interferon gamma-activated THP-1 macrophages. Our data indicate that preexposure to a low pH has a positive impact on subsequent challenge of L. monocytogenes with macrophagic cells.

Adaptation, Physiological↗