Klebsiella pneumoniae peptide hijacks a Streptococcus pneumoniae permease to subvert pneumococcal growth and colonization

• Published in: Communications biology Vol. 7; no. 1; p. 425
• Main Authors: Lux, Janine, Portmann, Hannah, Sánchez García, Lucía, Erhardt, Maria, Holivololona, Lalaina, Laloli, Laura, Licheri, Manon F., Gallay, Clement, Hoepner, Robert, Croucher, Nicholas J., Straume, Daniel, Veening, Jan-Willem, Dijkman, Ronald, Heller, Manfred, Grandgirard, Denis, Leib, Stephen L., Hathaway, Lucy J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38; 38/39; 631/326/1320; 631/326/421; 82/80; Amino acids; Animals; Antibiotic resistance; Antibiotics; Bacteriostats; Biomedical and Life Sciences; Cell size; Cerebrospinal fluid; Clinical isolates; Colonization; Disease resistance; Dysbacteriosis; Epithelial cells; Genetic transformation; Humans; Inflammation; Klebsiella pneumoniae; Life Sciences; Lysis; Membrane Transport Proteins - metabolism; Nasopharynx; Nasopharynx - microbiology; Peptides; Peptides - metabolism; Peptides - pharmacology; Permease; Pneumococcal Infections - microbiology; Pneumolysin; Rats; Respiratory tract; Secretome; Streptococcus infections; Streptococcus pneumoniae; Toxicity
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06113-9

Treatment of pneumococcal infections is limited by antibiotic resistance and exacerbation of disease by bacterial lysis releasing pneumolysin toxin and other inflammatory factors. We identified a previously uncharacterized peptide in the Klebsiella pneumoniae secretome, which enters Streptococcus pneumoniae via its AmiA-AliA/AliB permease. Subsequent downregulation of genes for amino acid biosynthesis and peptide uptake was associated with reduction of pneumococcal growth in defined medium and human cerebrospinal fluid, irregular cell shape, decreased chain length and decreased genetic transformation. The bacteriostatic effect was specific to S. pneumoniae and Streptococcus pseudopneumoniae with no effect on Streptococcus mitis, Haemophilus influenzae, Staphylococcus aureus or K. pneumoniae . Peptide sequence and length were crucial to growth suppression. The peptide reduced pneumococcal adherence to primary human airway epithelial cell cultures and colonization of rat nasopharynx, without toxicity. We identified a peptide with potential as a therapeutic for pneumococcal diseases suppressing growth of multiple clinical isolates, including antibiotic resistant strains, while avoiding bacterial lysis and dysbiosis. A Klebsiella pneumoniae peptide enters Streptococcus pneumoniae via its AmiA-AliA/AliB permease reducing pneumococcal growth, adherence to primary human airway epithelial cells, colonization of rat nasopharynx and genetic transformation.