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.