Synthetic peptide V11A reduces bacterial load and inflammation in pneumococcal meningitis

Introduction: Pneumococcal meningitis, caused by Streptococcus pneumoniae, is exacerbated by factors released during bacterial lysis, triggering inflammation and damage to host cells. Bacteriolytic antibiotics increase inflammation meaning that there is a high unmet medical need for non-bacteriolytic antimicrobials as alternative therapeutic options. Previously, an 11-amino acid peptide was discovered in the secretome of Klebsiella pneumoniae, named V11A, and was found to inhibit growth of S. pneumoniae in a bacteriostatic and species-specific manner in vitro. Methods and Results: Here it is shown that peptide V11A reduced the growth of not only S. pneumoniae spiked into human cerebrospinal fluid (hCSF) of non-meningitis donors but also S. pneumoniae present naturally in hCSF of a patient with pneumococcal meningitis (hmCSF). In an infant rat model of pneumococcal meningitis, V11A not only reduced the number of S. pneumoniae bacteria in CSF and blood but also reduced the concentration of cytokines GRO/KC/CINC-1 (an interleukin-8 (IL-8)-like cytokine in rats) and IL-10 in CSF. Discussion: Our results support the potential of therapeutic peptide to reduce the bacterial burden and mitigate the inflammatory response in pneumococcal meningitis.