Campycins are novel broad-spectrum antibacterials killing Campylobacter jejuni

Athina Zampara, Yilmaz Emre Gencay, Lone Brøndsted, Martine Camilla Holst Sørensen*

*Corresponding author for this work

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Abstract

Abstract: Pyocins are high molecular weight bacteriocins produced by Pseudomonas aeruginosa that can be retargeted to new bacterial species by exchanging the pyocin tail fibers with bacteriophage receptor binding proteins (RBPs). Here, we develop retargeted pyocins called campycins as new antibacterials to precisely and effectively kill the major foodborne pathogen Campylobacter jejuni. We used two diverse RBPs (H-fibers) encoded by CJIE1 prophages found in the genomes of C. jejuni strains CAMSA2147 and RM1221 to construct campycin 1 and campycin 2, respectively. Campycins 1 and 2 could target all C. jejuni strains tested due to complementary antibacterial spectra. In addition, both campycins led to more than 3 log reductions in C. jejuni counts under microaerobic conditions at 42 °C, whereas the killing efficiency was less efficient under anaerobic conditions at 5 °C. Furthermore, we discovered that both H-fibers used to construct the campycins bind to the essential major outer membrane protein (MOMP) present in all C. jejuni in a strain-specific manner. Protein sequence alignment and structural modeling suggest that the highly variable extracellular loops of MOMP form the binding sites of the diverse H-fibers. Further in silico analyses of 5000 MOMP sequences indicated that the protein falls into three major clades predicted to be targeted by either campycin 1 or campycin 2. Thus, campycins are promising antibacterials against C. jejuni and are expected to broadly target numerous strains of this human pathogen in nature and agriculture. Key points: • Campycins are engineered R-type pyocins containing H-fibers from C. jejuni prophages • Campycins reduce C. jejuni counts by >3 logs at conditions promoting growth • Campycins bind to the essential outer membrane protein MOMP in a strain-dependent way

Original languageEnglish
Article number484
JournalApplied Microbiology and Biotechnology
Volume108
Number of pages14
ISSN0175-7598
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

Keywords

  • H-fiber
  • porA
  • Prophage CJIE1
  • Pyocin
  • Receptor-binding protein
  • Tail fiber protein H

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