Bps polysaccharide of <i>Bordetella pertussis</i> resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts <i>Escherichia coli</i> into a respiratory pathogen
Bibliographic record
Abstract
Abstract Infections and disease caused by the obligate human pathogen Bordetella pertussis (Bp) are increasing, despite widespread vaccinations. The current acellular pertussis vaccines remain ineffective against nasopharyngeal colonization, carriage, and transmission. In this work, we tested the hypothesis that Bordetella polysaccharide (Bps), a member of the poly-β-1,6- A -acetyl-D-glucosamine (PNAG/PGA) family of polysaccharides promotes respiratory tract colonization of Bp by resisting killing by antimicrobial peptides (AMPs). Genetic deletion of the bpsA-D locus, as well as treatment with the specific glycoside hydrolase Dispersin B, increased susceptibility to AMP-mediated killing. Bps was found to be both cell surface-associated and secreted during laboratory growth and mouse infections. Addition of bacterial supernatants containing Bps and purified Bps increased B. pertussis resistance to AMPs. By utilizing ELISA, immunoblot and flow cytometry assays, we show that Bps functions as a dual surface shield and decoy by inhibiting AMP binding. Co-inoculation of C57BL/6J mice with a Bps-proficient strain enhanced respiratory tract survival of the Bps-deficient strain. In combination, the presented results highlight the critical role of Bps as a central driver of B. pertussis pathogenesis. Heterologous production of Bps in a non-pathogenic E. coli K12 strain increased AMP resistance in vitro, and augmented bacterial survival and pathology in the mouse respiratory tract. Therefore, by conferring virulence traits across bacterial genera, Bps transforms a primarily intestinal and urinary tract bacterium into a respiratory pathogen. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps. Author summary Pertussis or whooping cough, caused by the obligate human pathogen Bordetella pertussis (Bp), is resurging in many countries. Currently, the mechanism by which B. pertussis subverts and resists host immunity is poorly known. In this manuscript, we examined the role of the B. pertussis polysaccharide Bps in promoting resistance to antimicrobial peptides (AMPs), a critical component of host immune defense. We show that the presence of Bps on the bacterial cell surface enhanced AMP resistance. Bps was secreted both during bacterial growth and during mouse infections. We further found that Bps functioned both as a surface shield and decoy, thereby inhibiting AMP binding. Simultaneous infection of mice with Bps-proficient and Bps- deficient strains resulted in greater survival of the Bps-deficient strain in the mouse respiratory tract. Finally, production of Bps in a non-pathogenic E. coli strain increased AMP resistance in vitro, and increased bacterial survival and heightened pathology in the mouse respiratory tract. Our study provides new insights into how B. pertussis has evolved to survive in the mammalian respiratory tract. Additionally, these studies underscore the potential of a single virulence factor to convert a non-pathogenic bacterium into a respiratory tract pathogen.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".