Abstract
Purpose :
Microbial keratitis is a leading cause of cornel blindness worldwide. Streptococcus pneumoniae is a gram positive, ubiquitous human pathogen, and a leading cause of bacterial keratitis. Corneal infections by S. pneumoniae are extremely aggressive despite their antibiotic sensitivity and increased resistance towards various classes of antibiotics has being reported. The World Health Organization has listed S. pneumoniae as a critical antibiotic resistant species that requires an immediate attention for development of new therapeutics. S100A12, an antimicrobial peptide (AMP) and a Ca+2 binding host-defense protein, exhibits antimicrobial effects against various pathogens and initiate a pro-inflammatory immune response. Here, we aim to determine the role of S100A12 against S. pneumoniae.
Methods :
In-vitro expression of S100A12 in patients and corneal epithelial cells (HCEC) was determined by immunofluorescence assays and qPCR. The effect of S100A12 on S. pneumoniae was studied by colony forming units, scanning electron microscope (SEM) imaging, flow cytometry and biochemical assays. The immune modulatory properties of the S100A12 was studied by cell migration assay and western blot in HCEC.
Results :
We found an increased protein expression of S100A12 in corneal tissues obtained from patient with S. pneumoniae keratitis and HCECs upon S. pneumoniae infection. S100A12 inhibited the bacterial growth and the biofilm formation. It induced the ROS generation within bacteria. It caused damage of the bacterial membrane as observed by SEM. S100A12 accelerated the cell migration and wound closure in HCECs and activated the MAPK signalling pathway.
Conclusions :
S100A12 showed antibacterial effect on S. pneumoniae in-vitro and caused membrane damage. It also exhibited immune-modulatory properties and exhibits promising potential as an alternative therapeutic intervention against S. pneumoniae.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.