Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018

Abstract

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Keywords: Bordetella pertussis; Spain; bacteria; pertussis vaccine; phylogenetic evolution; virulence factors; whooping cough.

Figure 1

Temporal distribution of pertactin-deficient Bordetella pertussis isolates in Spain, 1986–2018. ACV, acellular vaccine WCV, whole-cell vaccine.

Figure 2

Temporal distribution of pertactin-deficient isolates and temporal trend of molecular mechanisms of pertactin deficiency in pertactin-deficient Bordetella pertussis isolates in Spain, 2006–2018 (study period 3). Del, deletion; fwd, forward; inv, inversion; IS, insertion sequence; prn, pertactin gene: rev, reverse.

Figure 3

Time-scaled phylogeny of Bordetella pertussis isolates collected in Spain, 1986–2018. A) Bayesian phylogenetic reconstruction of 184 B. pertussis isolates and the reference Tohama I (GenBank accession no. NZ_CP031787). Shaded regions indicate periods of WCV, WCV/ACV, and ACV use. Colored dots at the end of the tree branches indicate pertactin production for each isolate. Alleles of ptxA, ptxP, prn, fim2, and fim3 are indicated for each isolate, on the right. Data associated with expression (serotyping) of FIM2/FIM3 are also indicated for each isolate; B) Temporal distribution of the isolates’ clades of B. pertussis based on the vaccine type(s) used for routine vaccination. ACV, acellular vaccine; del, deletion; FIM, fimbrial serotype; fwd, forward; inv, inversion; IS, insertion sequence; MRCA, most recent common ancestor; prn, pertactin gene: rev, reverse; WCV, whole-cell vaccine.

Figure 4

Temporal distribution of fimbrial serotypes and frequency of pertactin-deficient Bordetella pertussis isolates collected in Spain, 2006–2018 (study period 3). FIM, fimbrial serotype.