Whooping cough is a vaccine-preventable disease due to Bordetella pertussis and B. parapertussis. This highly contagious respiratory disease occurs through epidemic cycles every 3–5 years and ...vaccination did not change this frequency. Models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. However, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine pressure might also play an important role. These parameters are discussed in this review.
Adaptation and evolution of two Bordetella species causing pertussis.
Abstract
The genus
Bordetella
includes bacteria that are found in the environment and/or associated with humans and other animals. A few closely related species, including
Bordetella pertussis
, are ...human pathogens that cause diseases such as whooping cough. Here, we present a large database of
Bordetella
isolates and genomes and develop genotyping systems for the genus and for the
B. pertussis
clade. To generate the database, we merge previously existing databases from Oxford University and Institut Pasteur, import genomes from public repositories, and add 83 newly sequenced
B. bronchiseptica
genomes. The public database currently includes 2582
Bordetella
isolates and their provenance data, and 2085 genomes (
https://bigsdb.pasteur.fr/bordetella/
). We use core-genome multilocus sequence typing (cgMLST) to develop genotyping systems for the whole genus and for
B. pertussis
, as well as specific schemes to define antigenic, virulence and macrolide resistance profiles. Phylogenetic analyses allow us to redefine evolutionary relationships among known
Bordetella
species, and to propose potential new species. Our database provides an expandable resource for genotyping of environmental and clinical
Bordetella
isolates, thus facilitating evolutionary and epidemiological research on whooping cough and other
Bordetella
infections.
Bordetella pertussis causes whooping cough, a highly contagious respiratory disease that is reemerging in many world regions. The spread of antigen-deficient strains may threaten acellular vaccine ...efficacy. Dynamics of strain transmission are poorly defined because of shortcomings in current strain genotyping methods. Our objective was to develop a whole-genome genotyping strategy with sufficient resolution for local epidemiologic questions and sufficient reproducibility to enable international comparisons of clinical isolates. We defined a core genome multilocus sequence typing scheme comprising 2,038 loci and demonstrated its congruence with whole-genome single-nucleotide polymorphism variation. Most cases of intrafamilial groups of isolates or of multiple isolates recovered from the same patient were distinguished from temporally and geographically cocirculating isolates. However, epidemiologically unrelated isolates were sometimes nearly undistinguishable. We set up a publicly accessible core genome multilocus sequence typing database to enable global comparisons of B. pertussis isolates, opening the way for internationally coordinated surveillance.
Bordetella pertussis, a human pathogenic bacterium, produces either one or two types of serologically distinct fimbriae, Fim2 and Fim3, as virulence factors. The expression of fim2 and fim3 is ...regulated by the BvgAS two-component system and the length of poly(C) stretches in Pfim promoters. In the Bvg+ phase, B. pertussis virulence-activated genes (vags) are up-regulated and virulence-repressed genes (vrgs) are down-regulated. Previous studies have shown that fim2 is a vag, but there is no consensus on fim3 regulation. We examined the regulation of fimbrial expression in B. pertussis clinical isolates. Our findings indicate that fim2 is a vag, while fim3 is a vag when Pfim3 poly(C)>13C, and a vrg when poly(C)≤13C. Although increased fim3 expression was observed in the Bvg- phase in isolates with Pfim3 poly(C)≤13C, Fim3 production was not detected, suggesting post-transcriptional regulation of fim3 expression. These findings provide an insight into the regulation of fimbrial expression in B. pertussis.
A group of six clinical isolates previously identified as Corynebacterium diphtheriae biovar Belfanti, isolated from human cutaneous or peritoneum infections and from one dog, were characterized by ...genomic sequencing, biochemical analysis and MALDI-TOF mass spectrometry. The six isolates were negative for the diphtheria toxin gene. Phylogenetic analyses showed that the six isolates (including FRC0190T) are clearly demarcated from C. diphtheriae, Corynebacterium belfantii, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis. The average nucleotide identity of FRC0190T with C. diphtheriae NCTC11397T was 92.6%, and was 91.8% with C. belfantii FRC0043T. C. diphtheriae subsp. lausannense strain CHUV2995T appeared to be a later heterotypic synonym of C. belfantii (ANI, 99.3%). Phenotyping data revealed an atypical negative or heterogeneous intermediate maltose fermentation reaction for the six isolates. MALDI-TOF mass spectrometry differentiated the new group from the other Corynebacterium taxa by the presence of specific spectral peaks. rpoB sequences showed identity to atypical, maltose-negative C. diphtheriae biovar Belfanti isolates previously described from two cats in the USA. We propose the name Corynebacterium rouxii sp. nov. for the novel group, with FRC0190T (= CIP 111752T = DSM 110354T) as type strain.
Bordetella pertussis still circulates worldwide despite vaccination. Fimbriae are components of some acellular pertussis vaccines. Population fluctuations of B. pertussis fimbrial serotypes (FIM2 and ...FIM3) are observed, and fim3 alleles (fim3-1 clade 1 and fim3-2 clade 2) mark a major phylogenetic subdivision of B. pertussis.
To compare microbiological characteristics and expressed protein profiles between fimbrial serotypes FIM2 and FIM3 and genomic clades.
A total of 19 isolates were selected. Absolute protein abundance of the main virulence factors, autoagglutination and biofilm formation, bacterial survival in whole blood, induced blood cell cytokine secretion, and global proteome profiles were assessed.
Compared to FIM3, FIM2 isolates produced more fimbriae, less cellular pertussis toxin subunit 1 and more biofilm, but auto-agglutinated less. FIM2 isolates had a lower survival rate in cord blood, but induced higher levels of IL-4, IL-8 and IL-1β secretion. Global proteome comparisons uncovered 15 differentially produced proteins between FIM2 and FIM3 isolates, involved in adhesion and metabolism of metals. FIM3 isolates of clade 2 produced more FIM3 and more biofilm compared to clade 1.
FIM serotype and fim3 clades are associated with proteomic and other biological differences, which may have implications on pathogenesis and epidemiological emergence.
The recent increase in pertussis cases observed in some countries may have several causes, including the evolution of
populations towards escape of vaccine-induced immunity. Most genomic studies of
...isolates performed so far are from countries that use acellular vaccines. The objective was to analyse genomic sequences of isolates collected during the 2014 whooping cough epidemic in Tunisia, a country where whole-cell vaccines are used. Ten Tunisian isolates and four vaccine strains were sequenced and compared to 169 isolates from countries where acellular vaccines are used. Phylogenetic analysis showed that Tunisian isolates are diverse, demonstrating a multi-strain 2014 epidemic peak, and are intermixed with those circulating in other world regions, showing inter-country transmission. Consistently, Tunisian isolates have antigen variant composition observed in other world regions. No pertactin-deficient strain was observed. The Tunisian
population appears to be largely connected with populations from other countries.
Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed ...worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. IMPORTANCE Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.
can cause invasive infections but can also be isolated from the respiratory tract of patients with whooping-cough like symptoms. For the first time, we describe the lipid A structure of
reference ...strain ATCC 51541 (alias NCTC12912 or CIP104394) and those of three French
clinical isolates originating from blood (Bho1) or from respiratory samples (FR4020 and FR4101). They were investigated using chemical analyses, gas chromatography-mass spectrometry (GC-MS), and matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS). The analyses revealed a common bisphosphorylated
-(1→6)-linked d-glucosamine disaccharide with hydroxytetradecanoic acid in amide linkages. Similar to
,
and
lipids A, the hydroxytetradecanoic acid at the C-2' position are carrying in secondary linkage a 2-hydroxytetradecanoic acid residue resulting of post-traductional biosynthesis modifications. The three clinical isolates displayed characteristic structural traits compared to the ATCC 51541 reference strain: the lipid A phosphate groups are more or less modified with glucosamine in the isolates and reference strain, but the presence of 10:0(3-OH) is only observed in the isolates. This trait was only described in
and
strains, as well as in
isolates by the past. The genetic bases for most of the key structural elements of lipid A were analyzed and supported the structural data.
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