The commensal pathogen S. pneumoniae may cause otitis media, pneumonia, bacteremia and meningitis by either spreading to or invading the respective tissues. The invasion is mediated by bacterial adhesion to and subsequent transcytosis through the epithelial cells. In our previous studies several proteins, found to be cell wall localized, could be classified as adhesins. One such adhesin is Phosphoenol-pyruvate Phospho-transferase A (PtsA), in addition to its function as the first enzyme of the PTS system. In the current study putative target receptor molecules for PtsA were identified on the surface of host cells using phage library of random peptides followed by homology based search of the human genome. Five out of 6 identified putative target molecules for PtsA were found to reside in the lung derived epithelial cells using immunostaining. Microscale Thermophoresis (MST) assay confirmed the specificity of rPtsA binding to each peptide with affinities in the micro-molar range, which is in accordance with their inhibition of adhesion concentration range. In addition, in vivo experiments exhibited lower bacterial load in mice infected with S. pneumoniae preincubated with putative receptor derived peptides, indicating the essential role of PtsA in bacterial adhesion and subsequent infection. The increasing antibiotic resistance of S. pneumoniae pathogen, the major cause of some life threatening diseases, albeit the currently existing vaccines, encourages the development of new therapies. The putative target receptor derived peptides are currently considered as candidates for potential effective therapeutics in the future.
