Klebsiella pneumoniae peptide hijacks a Streptococcus pneumoniae permease to subvert pneumococcal growth and colonization.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
08 Apr 2024
08 Apr 2024
Historique:
received:
22
11
2023
accepted:
26
03
2024
medline:
9
4
2024
pubmed:
9
4
2024
entrez:
8
4
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38589539
doi: 10.1038/s42003-024-06113-9
pii: 10.1038/s42003-024-06113-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
425Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 192067
Informations de copyright
© 2024. The Author(s).
Références
Willyard, C. The drug-resistant bacteria that pose the greatest health threats. Nature 543, 15 (2017).
pubmed: 28252092
doi: 10.1038/nature.2017.21550
Eleraky, N. E., Allam, A., Hassan, S. B. & Omar, M. M. Nanomedicine fight against antibacterial resistance: an overview of the recent pharmaceutical innovations. Pharmaceutics 12, 142 (2020).
pubmed: 32046289
pmcid: 7076477
doi: 10.3390/pharmaceutics12020142
World Health Organization. WHO Publishes List of Bacteria for Which New Antibiotics are Urgently Needed https://www.who.int/en/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed (2017).
Asokan, G. V., Ramadhan, T., Ahmed, E. & Sanad, H. WHO Global Priority Pathogens List: a bibliometric analysis of medline-pubmed for knowledge mobilization to infection prevention and control practices in Bahrain. Oman Med. J. 34, 184–193 (2019).
pubmed: 31110624
pmcid: 6505350
doi: 10.5001/omj.2019.37
van der Poll, T. & Opal, S. M. Pathogenesis, treatment, and prevention of pneumococcal pneumonia. Lancet 374, 1543–1556 (2009).
pubmed: 19880020
doi: 10.1016/S0140-6736(09)61114-4
Cillóniz, C., Garcia-Vidal, C., Ceccato, A. & Torres, A. Antimicrobial resistance among Streptococcus pneumoniae in Antimicrobial Resistance in the 21st Century (eds. Fong, I., Shlaes, D., Drlica, K.) 13–38 (Springer, 2018).
Brugger, S. D. et al. Dolosigranulum pigrum cooperation and competition in human nasal microbiota. mSphere 5, e00852–00820 (2020).
pubmed: 32907957
pmcid: 7485692
doi: 10.1128/mSphere.00852-20
Raya Tonetti, F. et al. The respiratory commensal bacterium Dolosigranulum pigrum 040417 improves the innate immune response to Streptococcus pneumoniae. Microorganisms 9, 1324 (2021).
pubmed: 34207076
pmcid: 8234606
doi: 10.3390/microorganisms9061324
Horn, K. J. et al. Corynebacterium species inhibit Streptococcus pneumoniae colonization and infection of the mouse airway. Front. Microbiol. 12, 804935 (2021).
pubmed: 35082772
doi: 10.3389/fmicb.2021.804935
Santagati, M., Scillato, M., Patanè, F., Aiello, C. & Stefani, S. Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol. Med. Microbiol. 65, 23–31 (2012).
pubmed: 22243526
doi: 10.1111/j.1574-695X.2012.00928.x
Horn, K. J., Schopper, M. A., Drigot, Z. G. & Clark, S. E. Airway Prevotella promote TLR2-dependent neutrophil activation and rapid clearance of Streptococcus pneumoniae from the lung. Nat. Commun. 13, 3321 (2022).
pubmed: 35680890
pmcid: 9184549
doi: 10.1038/s41467-022-31074-0
Claverys, J. P., Grossiord, B. & Alloing, G. Is the Ami-AliA/B oligopeptide permease of Streptococcus pneumoniae involved in sensing environmental conditions? Res. Microbiol. 151, 457–463 (2000).
pubmed: 10961459
doi: 10.1016/S0923-2508(00)00169-8
Kerr, A. R. et al. The Ami-AliA/AliB permease of Streptococcus pneumoniae is involved in nasopharyngeal colonization but not in invasive disease. Infect. Immun. 72, 3902–3906 (2004).
pubmed: 15213133
pmcid: 427416
doi: 10.1128/IAI.72.7.3902-3906.2004
Nasher, F., Heller, M. & Hathaway, L. J. Streptococcus pneumoniae proteins AmiA, AliA, and AliB bind peptides found in ribosomal proteins of other bacterial species. Front. Microbiol. 8, 2688 (2018).
pubmed: 29379482
pmcid: 5775242
doi: 10.3389/fmicb.2017.02688
Nasher, F. et al. Peptide ligands of AmiA, AliA, and AliB proteins determine pneumococcal phenotype. Front. Microbiol. 9, 3013 (2018).
pubmed: 30568648
pmcid: 6290326
doi: 10.3389/fmicb.2018.03013
Lux, J. et al. AmiA and AliA peptide ligands are secreted by Klebsiella pneumoniae and inhibit growth of Streptococcus pneumoniae. Sci. Rep. 12, 22268 (2022).
pubmed: 36564446
pmcid: 9789142
doi: 10.1038/s41598-022-26838-z
Domenech, A., Slager, J. & Veening, J. W. Antibiotic-induced cell chaining triggers pneumococcal competence by reshaping quorum sensing to autocrine-like signaling. Cell Rep. 25, 2390–2400.e2393 (2018).
pubmed: 30485808
pmcid: 6289044
doi: 10.1016/j.celrep.2018.11.007
Slager, J., Aprianto, R. & Veening, J.-W. Refining the pneumococcal competence regulon by RNA sequencing. J. Bacteriol. 201, e00780–00718 (2019).
pubmed: 30885934
pmcid: 6560143
doi: 10.1128/JB.00780-18
Winkler, M. E. & Morrison, D. A. Competence beyond genes: filling in the details of the pneumococcal competence transcriptome by a systems approach. J. Bacteriol. 201, e00238–00219 (2019).
pubmed: 30988030
pmcid: 6560134
doi: 10.1128/JB.00238-19
Kwun, M. J., Ion, A. V., Oggioni, M. R., Bentley, S. D. & Croucher, N. J. Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae. Nucleic Acids Res. 51, 10375–10394 (2023).
pubmed: 37757859
pmcid: 10602874
doi: 10.1093/nar/gkad760
Gultom, M., Laloli, L. & Dijkman, R. Well-differentiated primary mammalian airway epithelial cell cultures. Methods Mol. Biol. 2203, 119–134 (2020).
pubmed: 32833209
doi: 10.1007/978-1-0716-0900-2_10
Rayamajhi, M., Zhang, Y. & Miao, E. A. Detection of pyroptosis by measuring released lactate dehydrogenase activity. Methods Mol. Biol. 1040, 85–90 (2013).
pubmed: 23852598
pmcid: 3756820
doi: 10.1007/978-1-62703-523-1_7
Basnet, R. M., Zizioli, D., Taweedet, S., Finazzi, D. & Memo, M. Zebrafish larvae as a behavioral model in neuropharmacology. Biomedicines 7, 23 (2019).
pubmed: 30917585
pmcid: 6465999
doi: 10.3390/biomedicines7010023
Rock, S., Rodenburg, F., Schaaf, M. J. M. & Tudorache, C. Detailed analysis of Zebrafish larval behaviour in the light dark challenge assay shows that diel hatching time determines individual variation. Front. Physiol. 13, 827282 (2022).
pubmed: 35480044
pmcid: 9036179
doi: 10.3389/fphys.2022.827282
Rodriguez, J. L., Dalia, A. B. & Weiser, J. N. Increased chain length promotes pneumococcal adherence and colonization. Infect. Immun. 80, 3454–3459 (2012).
pubmed: 22825449
pmcid: 3457561
doi: 10.1128/IAI.00587-12
Hauge, I. H. et al. A novel proteinaceous molecule produced by Lysinibacillus sp. OF-1 depends on the Ami oligopeptide transporter to kill Streptococcus pneumoniae. Microbiology (Reading) 169, 001313 (2023).
pubmed: 36881456
doi: 10.1099/mic.0.001313
Baltzer, S. A. & Brown, M. H. Antimicrobial peptides: promising alternatives to conventional antibiotics. J. Mol. Microbiol. Biotechnol. 20, 228–235 (2011).
pubmed: 21894027
Hirst, R. A., Kadioglu, A., O’Callaghan, C. & Andrew, P. W. The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin. Exp. Immunol. 138, 195–201 (2004).
pubmed: 15498026
pmcid: 1809205
doi: 10.1111/j.1365-2249.2004.02611.x
Tabusi, M. et al. Neuronal death in pneumococcal meningitis is triggered by pneumolysin and RrgA interactions with β-actin. PLoS Pathog. 17, e1009432 (2021).
pubmed: 33760879
pmcid: 7990213
doi: 10.1371/journal.ppat.1009432
Leib, S. L. & Täuber, M. G. Pathogenesis of bacterial meningitis. Infect. Dis. Clin. North Am. 13, 527–548 (1999).
pubmed: 10470554
doi: 10.1016/S0891-5520(05)70093-3
Green, A. E. et al. Airway metabolic profiling during Streptococcus pneumoniae infection identifies branched chain amino acids as signatures of upper airway colonisation. PLoS Pathog. 19, e1011630 (2023).
pubmed: 37669280
pmcid: 10503754
doi: 10.1371/journal.ppat.1011630
Al-Bayati, F. A. et al. Pneumococcal galactose catabolism is controlled by multiple regulators acting on pyruvate formate lyase. Sci. Rep. 7, 43587 (2017).
pubmed: 28240278
pmcid: 5327383
doi: 10.1038/srep43587
Heath, R. J., White, S. W. & Rock, C. O. Lipid biosynthesis as a target for antibacterial agents. Prog. Lipid Res. 40, 467–497 (2001).
pubmed: 11591436
doi: 10.1016/S0163-7827(01)00012-1
Aggarwal, S. D. et al. Competence-associated peptide BriC alters fatty acid biosynthesis in Streptococcus pneumoniae. mSphere 6, e0014521 (2021).
pubmed: 34192504
doi: 10.1128/mSphere.00145-21
Liu, X. et al. High-throughput CRISPRi phenotyping identifies new essential genes in Streptococcus pneumoniae. Mol. Syst. Biol. 13, 931 (2017).
pubmed: 28490437
pmcid: 5448163
doi: 10.15252/msb.20167449
Piotrowski, A., Luo, P. & Morrison, D. A. Competence for genetic transformation in Streptococcus pneumoniae: termination of activity of the alternative sigma factor ComX is independent of proteolysis of ComX and ComW. J. Bacteriol. 191, 3359–3366 (2009).
pubmed: 19286798
pmcid: 2687157
doi: 10.1128/JB.01750-08
Attaiech, L. et al. Role of the single-stranded DNA-binding protein SsbB in pneumococcal transformation: maintenance of a reservoir for genetic plasticity. PLoS Genet. 7, e1002156 (2011).
pubmed: 21738490
pmcid: 3128108
doi: 10.1371/journal.pgen.1002156
Stevens, K. E., Chang, D., Zwack, E. E. & Sebert, M. E. Competence in Streptococcus pneumoniae Is regulated by the rate of ribosomal decoding errors. mBio 2, e00071–00011 (2011).
pubmed: 21933920
pmcid: 3175624
doi: 10.1128/mBio.00071-11
Kausmally, L., Johnsborg, O., Lunde, M., Knutsen, E. & Havarstein, L. S. Choline-binding protein D (CbpD) in Streptococcus pneumoniae is essential for competence-induced cell lysis. J. Bacteriol. 187, 4338–4345 (2005).
pubmed: 15968042
pmcid: 1151764
doi: 10.1128/JB.187.13.4338-4345.2005
Johnsborg, O., Eldholm, V., Bjørnstad, M. L. & Håvarstein, L. S. A predatory mechanism dramatically increases the efficiency of lateral gene transfer in Streptococcus pneumoniae and related commensal species. Mol. Microbiol. 69, 245–253 (2008).
pubmed: 18485065
doi: 10.1111/j.1365-2958.2008.06288.x
Eldholm, V., Johnsborg, O., Haugen, K., Ohnstad, H. S. & Havarstein, L. S. Fratricide in Streptococcus pneumoniae: contributions and role of the cell wall hydrolases CbpD, LytA and LytC. Microbiology (Reading) 155, 2223–2234 (2009).
pubmed: 19389766
doi: 10.1099/mic.0.026328-0
Biornstad, T. J., Ohnstad, H. S. & Havarstein, L. S. Deletion of the murein hydrolase CbpD reduces transformation efficiency in Streptococcus thermophilus. Microbiology (Reading) 158, 877–885 (2012).
pubmed: 22241050
doi: 10.1099/mic.0.056150-0
Cullin, N., Redanz, S., Lampi, K. J., Merritt, J. & Kreth, J. Murein hydrolase LytF of Streptococcus sanguinis and the ecological consequences of competence development. Appl. Environ. Microbiol. 83, e01709–e01717 (2017).
pubmed: 28986373
pmcid: 5717204
doi: 10.1128/AEM.01709-17
Zhu, Y. et al. CrfP, a fratricide protein, contributes to natural transformation in Streptococcus suis. Vet. Res. 52, 50 (2021).
pubmed: 33762005
pmcid: 7992943
doi: 10.1186/s13567-021-00917-x
Hendriksen, W. T. et al. CodY of Streptococcus pneumoniae: link between nutritional gene regulation and colonization. J. Bacteriol. 190, 590–601 (2008).
pubmed: 18024519
doi: 10.1128/JB.00917-07
Weiser, J. N., Ferreira, D. M. & Paton, J. C. Streptococcus pneumoniae: transmission, colonization and invasion. Nat. Rev. Microbiol. 16, 355–367 (2018).
pubmed: 29599457
pmcid: 5949087
doi: 10.1038/s41579-018-0001-8
Cundell, D. R., Pearce, B. J., Sandros, J., Naughton, A. M. & Masure, H. R. Peptide permeases from Streptococcus pneumoniae affect adherence to eucaryotic cells. Infect. Immun. 63, 2493–2498 (1995).
pubmed: 7790061
pmcid: 173333
doi: 10.1128/iai.63.7.2493-2498.1995
Kallio, A. et al. Role of Pht proteins in attachment of Streptococcus pneumoniae to respiratory epithelial cells. Infect. Immun. 82, 1683–1691 (2014).
pubmed: 24491577
pmcid: 3993382
doi: 10.1128/IAI.00699-13
Adamou, J. E. et al. Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis. Infect. Immun. 69, 949–958 (2001).
pubmed: 11159990
pmcid: 97974
doi: 10.1128/IAI.69.2.949-958.2001
Uchiyama, S. et al. The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion. J. Exp. Med. 206, 1845–1852 (2009).
pubmed: 19687228
pmcid: 2737157
doi: 10.1084/jem.20090386
Zhang, J. R., Idanpaan-Heikkila, I., Fischer, W. & Tuomanen, E. I. Pneumococcal licD2 gene is involved in phosphorylcholine metabolism. Mol. Microbiol. 31, 1477–1488 (1999).
pubmed: 10200966
doi: 10.1046/j.1365-2958.1999.01291.x
Engel, H. et al. A low-affinity penicillin-binding protein 2x variant is required for heteroresistance in Streptococcus pneumoniae. Antimicrob. Agents Chemother. 58, 3934–3941 (2014).
pubmed: 24777105
pmcid: 4068597
doi: 10.1128/AAC.02547-14
Engel, H. et al. Heteroresistance to fosfomycin is predominant in Streptococcus pneumoniae and depends on the murA1 gene. Antimicrob. Agents Chemother. 57, 2801–2808 (2013).
pubmed: 23571543
pmcid: 3716182
doi: 10.1128/AAC.00223-13
Mühlemann, K., Matter, H. C., Täuber, M. G. & Bodmer, T. Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998–1999. J. Infect. Dis. 187, 589–596 (2003).
pubmed: 12599075
doi: 10.1086/367994
Müller, A. et al. Pneumococcal serotype determines growth and capsule size in human cerebrospinal fluid. BMC Microbiol. 20, 16 (2020).
pubmed: 31959125
pmcid: 6971925
doi: 10.1186/s12866-020-1700-7
Ducret, A., Quardokus, E. M. & Brun, Y. V. MicrobeJ, a tool for high throughput bacterial cell detection and quantitative analysis. Nat. Microbiol. 1, 16077 (2016).
pubmed: 27572972
pmcid: 5010025
doi: 10.1038/nmicrobiol.2016.77
Kjos, M. et al. Expression of Streptococcus pneumoniae bacteriocins is induced by antibiotics via regulatory interplay with the competence system. PLoS Pathog. 12, e1005422 (2016).
pubmed: 26840404
pmcid: 4739728
doi: 10.1371/journal.ppat.1005422
Uldry, A.-C. et al. Effect of sample transportation on the proteome of human circulating blood extracellular vesicles. Int. J. Mol. Sci. 23, 4515 (2022).
pubmed: 35562906
pmcid: 9099550
doi: 10.3390/ijms23094515
Faria, M. et al. Acrylamide acute neurotoxicity in adult zebrafish. Sci. Rep. 8, 7918 (2018).
pubmed: 29784925
pmcid: 5962567
doi: 10.1038/s41598-018-26343-2
Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2021).
pmcid: 8728295
doi: 10.1093/nar/gkab1038