title: Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.
abstract: Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work was to evaluate the bactericidal effect of bovine lactoferrin (bLF) and the synthetic LF-peptides lactoferricin (LFcin17-30), lactoferrampin (LFampin265-284), and LFchimera against S. pneumoniae planktonic cells. The mechanism of damage was also investigated, as well as the impact of these peptides on the transcription levels of genes known to encode important virulence factors. S. pneumoniae planktonic cells were treated with bLF, LFcin17-30, LFampin265-284 and LFchimera at different time points. The viability of treated planktonic cells was assessed by dilution and plating (in CFU/ml). The interaction between LF and LF-peptides coupled to fluorescein was visualized using a confocal microscope and flow cytometry, whereas the damage at structural levels was observed by electron microscopy. Damage to bacterial membranes was further evaluated by membrane permeabilization by use of propidium iodide and flow cytometry, and finally, the expression of pneumococcal genes was evaluated by qRT-PCR. bLF and LFchimera were the best bactericidal agents. bLF and peptides interacted with bacteria causing changes in the shape and size of the cell and membrane permeabilization. Moreover, the luxS gene was down-regulated in bacteria treated with LF. In conclusion, LF and LFchimera have a bactericidal effect, and LF down-regulates genes involved in the pathogenicity of pneumococcus, thus demonstrating potential as new agents for the treatment of pneumococcal infections.
authors: Unidad de Investigación, Facultad de Medicina, Universidad Autónoma de Sinaloa, Cedros y Sauces, Fracc. Fresnos., C.P. 80246, Culiacán, Sinaloa, Mexico, nidialeon@uas.edu.mx.
authors: Nidia
authors: N
authors: León-Sicairos
authors: Uriel A
authors: UA
authors: Angulo-Zamudio
authors: Jorge E
authors: JE
authors: Vidal
authors: Cynthia A
authors: CA
authors: López-Torres
authors: Jan G M
authors: JG
authors: Bolscher
authors: Kamran
authors: K
authors: Nazmi
authors: Ruth
authors: R
authors: Reyes-Cortes
authors: Magda
authors: M
authors: Reyes-López
authors: Mireya
authors: M
authors: de la Garza
authors: Adrian
authors: A
authors: Canizalez-Román
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D013437:Carbon-Sulfur Lyases / Q000235:genetics; D002417:Cattle; D002648:Child; D015870:Gene Expression / Q000187:drug effects; D005798:Genes, Bacterial / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000188:drug therapy; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C502040:lactoferrampin; C082171:lactoferricin B; D007781:Lactoferrin; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria