Tracheal colonization factor A (TcfA) is a biomarker for rapid and specific detection of Bordetella pertussis

Sci Rep. 2020 Sep 14;10(1):15002. doi: 10.1038/s41598-020-72092-6.

Abstract

Pertussis is a highly contagious disease for which prompt, point-of-care diagnosis remains an unmet clinical need. Results from conventional test modalities (nucleic acid detection, serology, and culture) take hours to days. To overcome this challenge, we identified a new biomarker (tracheal colonization factor A, TcfA) for detection of Bordetella pertussis infection by lateral flow immunoassay (LFIA). We developed a library of 28 epitope-mapped monoclonal antibodies against TcfA and incorporated three antibodies into a LFIA. The LFIA did not cross-react with common bacterial or fungal organisms, but did react with nine distinct B. pertussis strains. The minimal linear epitope sequences targeted by the LFIA were conserved in 98% of 954 B. pertussis isolates collected across 12 countries from 1949-2017. The LFIA's limit of detection was 3.0 × 105 CFU/mL with B. pertussis cells in buffer, 6.2 × 105 CFU/mL with nasopharyngeal washes from a non-human primate model, and 2.3 ng/mL with recombinant TcfA. The LFIA reacted with patient nasopharyngeal swab specimens containing as few as 1.8 × 106 B. pertussis genomes/mL and showed no false-positives. Rapid (< 20 min) LFIA detection of TcfA as a biomarker for B. pertussis infection is feasible and may facilitate early detection of pertussis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Bacterial Proteins / immunology*
  • Biomarkers / analysis*
  • Bordetella pertussis* / genetics
  • Bordetella pertussis* / immunology
  • Bordetella pertussis* / pathogenicity
  • Buffers
  • Epitope Mapping
  • Humans
  • Immunoassay / methods*
  • Limit of Detection
  • Mice
  • Nasopharynx / microbiology
  • Papio
  • Rabbits
  • Sensitivity and Specificity
  • Virulence Factors, Bordetella / immunology*
  • Whooping Cough / diagnosis
  • Whooping Cough / microbiology*

Substances

  • Antibodies, Monoclonal
  • Bacterial Proteins
  • Biomarkers
  • Buffers
  • Virulence Factors, Bordetella
  • tracheal colonization factor, Bordetella pertussis