RESUMEN
AIMS: The objective of this research was to quantify the levels of circulating HspBP1 and anti-HspBP1 IgG in HIV-infected individuals and to correlate them with CD4 T cell counts and viral load, as well as to determine the kinetics of those proteins during acute phase. METHODS AND RESULTS: Sixty serum samples from HIV-positive outpatients, thirty with high viral load and thirty with low viral load were analysed. The HspBP1 and anti-HspBP1 were quantified by ELISA. To investigate the kinetic of HspBP1 and anti-HspBp1 during the acute phase, these proteins and antibodies were quantified in samples of a commercial seroconverting HIV panel. All dosages were compared with the CD4 and CD8 T cell counts and HIV viral load. The results indicated that HIV positive outpatients presented significant increase in HspBP1 and anti-HspBP1 serum levels, compared with uninfected healthy. HspBP1 and anti-HspBP1 were negatively correlated with CD4 counts and CD4:CD8 ratio. In the acute phase, HspBP1 became significantly elevated 15 days after HIV infection. CONCLUSIONS: These results indicate that the quantification of HspBP1 can be associated to others well-established parameters of the HIV progression. SIGNIFICANCE AND IMPACT OF THE STUDY: The discovery that HspBp1 and anti-HspBp1 are associated with progression of HIV infection is new and corroborates to validate the quantification of these proteins as an additional strategy in the management of the HIV infection.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/sangre , Anticuerpos Antivirales/sangre , Infecciones por VIH/sangre , VIH/inmunología , Adulto , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , VIH/aislamiento & purificación , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Carga ViralRESUMEN
Antimicrobial peptides (AMPs) are cationic peptides that kill bacteria with a broad spectrum of action, low toxicity to mammalian cells and exceptionally low rates of bacterial resistance. These features have led to considerable efforts in developing AMPs as an alternative antibacterial therapy. In vitro studies have shown that AMPs interfere with membrane bilayer integrity via several possible mechanisms, which are not entirely understood. We have performed the synthesis, membrane lysis measurements, and biophysical characterization of a novel hybrid peptide. These measurements show that PA-Pln149 does not form nanopores, but instead promotes membrane rupture. It causes fast rupture of the bacterial model membrane (POPG-rich) at concentrations 100-fold lower than that required for the disruption of mammalian model membranes (POPC-rich). Atomistic molecular dynamics (MD) simulations were performed for single and multiple copies of PA-Pln149 in the presence of mixed and pure POPC/POPG bilayers to investigate the concentration-dependent membrane disruption by the hybrid peptide. These simulations reproduced the experimental trend and provided a potential mechanism of action for PA-Pln149. It shows that the PA-Pln149 does not form nanopores, but instead promotes membrane destabilization through peptide aggregation and induction of membrane negative curvature with the collapse of the lamellar arrangement. The sequence of events depicted for PA-Pln149 may offer insights into the mechanism of action of AMPs previously shown to induce negative deformation of membrane curvature and often associated with peptide translocation via non-bilayer intermediate structures.
RESUMEN
AIMS: Characterization and purification of a new bacteriocin produced by Lactobacillus plantarum LP 31 strain, isolated from Argentinian dry-fermented sausage. METHODS AND RESULTS: Lactobacillus plantarum LP 31 strain produces an antimicrobial compound that inhibits the growth of food-borne pathogenic bacteria. It was inactivated by proteolytic enzymes, was stable to heat and catalase and exhibited maximum activity in the pH range from 5.0 to 6.0. Consequently, it was characterized as a bacteriocin. It was purified by RP (reverse-phase) solid-phase extraction, gel filtration chromatography and RP-HPLC. Plantaricin produced by Lact. plantarum LP 31 is a peptide with a molecular weight of 1558.85 Da as determined by Maldi-Tof mass spectrometry and contains 14 amino acid residues. It was shown to have a bactericidal effect against Pseudomonas sp., Staphylococcus aureus, Bacillus cereus and Listeria monocytogenes. CONCLUSIONS: The bacteriocin produced by Lact. plantarum LP 31 may be considered as a new plantaricin according to its low molecular weight and particular amino acid composition. SIGNIFICANCE AND IMPACT OF THE STUDY: In view of the interesting inhibitory spectrum of this bacteriocin and because of its good technological properties (resistance to heat and activity at acidic pH), this bacteriocin has potential applications as a biopreservative to prevent the growth of food-borne pathogens and food spoilage bacteria in certain food products.