Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen

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-N-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 released 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. 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. These studies can serve as a foundation for other PNAG/PGA polysaccharides and for the development of an effective Bp vaccine that includes Bps.

Dual-Uptake Mode of the Antibiotic Phazolicin Prevents Resistance Acquisition by Gram-Negative Bacteria

“…Moreover, several genes of the S. meliloti PPP cluster are likely involved in legume symbiosis, as indicated by a Tn-seq screen in the host Medicago truncatula ( 50 ). A similar barrier role was proposed for diverse surface polysaccharides in the protection of S. meliloti and other bacteria against membrane-disrupting AMPs ( 51 – 57 ). According to Tn-seq, the biosynthetic genes for the S. meliloti capsular polysaccharide KPS also contribute to fitness in the presence of PHZ although to a lesser extent than the PPP biosynthesis genes ( Fig.…”

Architecture and matrix assembly determinants of Bordetella pertussis biofilms on primary human airway epithelium

“…At 24 h post-infection and compared to the Δ fhaB strain, there was a greater reduction in the numbers of the Δ bpsA-D strain associated with the HBE cells. We have recently discovered that Bps promotes resistance to human anti-microbial peptides (AMPs) [ 42 ]. Production of many AMPs by human epithelial cells is induced upon bacterial infection under in vitro culture conditions and in vivo [ 43 ].…”

“…Cationic antimicrobial peptides (AMPs), key components of host airway defense, interact with negatively charged eDNA. We propose that Bps and eDNA, and their complexes, can sequester AMPs produced by HBE cells, thereby preventing them from interacting with the bacterial surface, resulting in protection of Bp cells from clearance [ 42 ]. We previously showed that Bps promotes resistance to serum-dependent killing and inhibits the deposition of complement [ 24 ].…”

A Comprehensive Review of Recent Research into the Effects of Antimicrobial Peptides on Biofilms—January 2020 to September 2023

“…They concluded that diverse, strain-specific responses to exogenous PUFAs may be an adaptive survival strategy in bacteria that fluctuate between fish and environmental niches [48]. Finally, Bordetella pertussis polysaccharide (Bps) was shown to resist AMP (LL-37, polymyxin B, HNP-1, and HNP-2) killing, helping 'shield' non-pathogenic K12 E. coli and increase in vivo bacterial survival in the respiratory tract [49].…”