scholarly journals Conserved Patterns of Symmetric Inversion in the Genome Evolution of Bordetella Respiratory Pathogens

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Michael R. Weigand ◽  
Yanhui Peng ◽  
Dhwani Batra ◽  
Mark Burroughs ◽  
Jamie K. Davis ◽  
...  
Keyword(s):  
Genome Evolution ◽  
Bordetella Pertussis ◽  
Gene Order ◽  
Chromosome Structure ◽  
Whooping Cough ◽  
The United States ◽  
Respiratory Pathogens ◽  
Structure Variation ◽  
Content Type ◽  
Is Elements

ABSTRACT Whooping cough (pertussis), primarily caused by Bordetella pertussis, has resurged in the United States, and circulating strains exhibit considerable chromosome structural fluidity in the form of rearrangement and deletion. The genus Bordetella includes additional pathogenic species infecting various animals, some even causing pertussis-like respiratory disease in humans; however, investigation of their genome evolution has been limited. We studied chromosome structure in complete genome sequences from 167 Bordetella species isolates, as well as 469 B. pertussis isolates, to gain a generalized understanding of rearrangement patterns among these related pathogens. Observed changes in gene order primarily resulted from large inversions and were only detected in species with genomes harboring multicopy insertion sequence (IS) elements, most notably B. holmesii and B. parapertussis. While genomes of B. pertussis contain >240 copies of IS481, IS elements appear less numerous in other species and yield less chromosome structural diversity through rearrangement. These data were further used to predict all possible rearrangements between IS element copies present in Bordetella genomes, revealing that only a subset is observed among circulating strains. Therefore, while it appears that rearrangement occurs less frequently in other species than in B. pertussis, these clinically relevant respiratory pathogens likely experience similar mutation of gene order. The resulting chromosome structural fluidity presents both challenges and opportunity for the study of Bordetella respiratory pathogens. IMPORTANCE Bordetella pertussis is the primary agent of whooping cough (pertussis). The Bordetella genus includes additional pathogens of animals and humans, including some that cause pertussis-like respiratory illness. The chromosome of B. pertussis has previously been shown to exhibit considerable structural rearrangement, but insufficient data have prevented comparable investigation in related species. In this study, we analyze chromosome structure variation in several Bordetella species to gain a generalized understanding of rearrangement patterns in this genus. Just as in B. pertussis, we observed inversions in other species that likely result from common mutational processes. We used these data to further predict additional, unobserved inversions, suggesting that specific genome structures may be preferred in each species.

scholarly journals The History of Bordetella pertussis Genome Evolution Includes Structural Rearrangement

2017 ◽  
Vol 199 (8) ◽  
Author(s):  
Michael R. Weigand ◽  
Yanhui Peng ◽  
Vladimir Loparev ◽  
Dhwani Batra ◽  
Katherine E. Bowden ◽  
...  
Keyword(s):  
United States ◽  
Nucleotide Sequence ◽  
Bordetella Pertussis ◽  
Gene Order ◽  
Complete Genome ◽  
Whooping Cough ◽  
The United States ◽  
Content Type ◽  
Nucleotide Sequence Diversity ◽  
Genome Assemblies

ABSTRACT Despite high pertussis vaccine coverage, reported cases of whooping cough (pertussis) have increased over the last decade in the United States and other developed countries. Although Bordetella pertussis is well known for its limited gene sequence variation, recent advances in long-read sequencing technology have begun to reveal genomic structural heterogeneity among otherwise indistinguishable isolates, even within geographically or temporally defined epidemics. We have compared rearrangements among complete genome assemblies from 257 B. pertussis isolates to examine the potential evolution of the chromosomal structure in a pathogen with minimal gene nucleotide sequence diversity. Discrete changes in gene order were identified that differentiated genomes from vaccine reference strains and clinical isolates of various genotypes, frequently along phylogenetic boundaries defined by single nucleotide polymorphisms. The observed rearrangements were primarily large inversions centered on the replication origin or terminus and flanked by IS481, a mobile genetic element with >240 copies per genome and previously suspected to mediate rearrangements and deletions by homologous recombination. These data illustrate that structural genome evolution in B. pertussis is not limited to reduction but also includes rearrangement. Therefore, although genomes of clinical isolates are structurally diverse, specific changes in gene order are conserved, perhaps due to positive selection, providing novel information for investigating disease resurgence and molecular epidemiology. IMPORTANCE Whooping cough, primarily caused by Bordetella pertussis, has resurged in the United States even though the coverage with pertussis-containing vaccines remains high. The rise in reported cases has included increased disease rates among all vaccinated age groups, provoking questions about the pathogen's evolution. The chromosome of B. pertussis includes a large number of repetitive mobile genetic elements that obstruct genome analysis. However, these mobile elements facilitate large rearrangements that alter the order and orientation of essential protein-encoding genes, which otherwise exhibit little nucleotide sequence diversity. By comparing the complete genome assemblies from 257 isolates, we show that specific rearrangements have been conserved throughout recent evolutionary history, perhaps by eliciting changes in gene expression, which may also provide useful information for molecular epidemiology.

scholarly journals Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Natalia Cattelan ◽  
Jamie Jennings-Gee ◽  
Purnima Dubey ◽  
Osvaldo M. Yantorno ◽  
Rajendar Deora
Keyword(s):  
Bordetella Pertussis ◽  
Biofilm Formation ◽  
Whooping Cough ◽  
Bacterial Colonization ◽  
The United States ◽  
Content Type ◽  
Vaccination Programs ◽  
First Time ◽  
Reciprocal Expression ◽  
Country Specific

ABSTRACT Pertussis, or whooping cough, caused by the obligate human pathogen Bordetella pertussis is undergoing a worldwide resurgence. The majority of studies of this pathogen are conducted with laboratory-adapted strains which may not be representative of the species as a whole. Biofilm formation by B. pertussis plays an important role in pathogenesis. We conducted a side-by-side comparison of the biofilm-forming abilities of the prototype laboratory strains and the currently circulating isolates from two countries with different vaccination programs. Compared to the reference strain, all strains examined herein formed biofilms at high levels. Biofilm structural analyses revealed country-specific differences, with strains from the United States forming more structured biofilms. Bacterial hyperaggregation and reciprocal expression of biofilm-promoting and -inhibitory factors were observed in clinical isolates. An association of increased biofilm formation with augmented epithelial cell adhesion and higher levels of bacterial colonization in the mouse nose and trachea was detected. To our knowledge, this work links for the first time increased biofilm formation in bacteria with a colonization advantage in an animal model. We propose that the enhanced biofilm-forming capacity of currently circulating strains contributes to their persistence, transmission, and continued circulation.

scholarly journals Bordetella pertussis Lipid A Glucosamine Modification Confers Resistance to Cationic Antimicrobial Peptides and Increases Resistance to Outer Membrane Perturbation

2014 ◽  
Vol 58 (8) ◽  
pp. 4931-4934 ◽  
Author(s):  
Nita R. Shah ◽  
Robert E. W. Hancock ◽  
Rachel C. Fernandez
Keyword(s):  
Immune System ◽  
Antimicrobial Peptides ◽  
Outer Membrane ◽  
Bordetella Pertussis ◽  
Lipid A ◽  
Whooping Cough ◽  
Human Immune System ◽  
Cationic Antimicrobial Peptides ◽  
Content Type ◽  
Membrane Perturbation

ABSTRACTBordetella pertussis, the causative agent of whooping cough, has many strategies for evading the human immune system. Lipopolysaccharide (LPS) is an important Gram-negative bacterial surface structure that activates the immune system via Toll-like receptor 4 and enables susceptibility to cationic antimicrobial peptides (CAMPs). We show modification of the lipid A region of LPS with glucosamine increased resistance to numerous CAMPs, including LL-37. Furthermore, we demonstrate that this glucosamine modification increased resistance to outer membrane perturbation.

scholarly journals The RNA Chaperone Hfq Is Required for Virulence of Bordetella pertussis

2013 ◽  
Vol 81 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Ilona Bibova ◽  
Karolina Skopova ◽  
Jiri Masin ◽  
Ondrej Cerny ◽  
David Hot ◽  
...  
Keyword(s):  
Bordetella Pertussis ◽  
Posttranscriptional Regulation ◽  
Noncoding Rna ◽  
Whooping Cough ◽  
Lethal Dose ◽  
Rna Chaperone ◽  
Content Type ◽  
Small Noncoding Rna ◽  
Mrna Targets

ABSTRACTBordetella pertussisis a Gram-negative pathogen causing the human respiratory disease called pertussis or whooping cough. Here we examined the role of the RNA chaperone Hfq inB. pertussisvirulence. Hfq mediates interactions between small regulatory RNAs and their mRNA targets and thus plays an important role in posttranscriptional regulation of many cellular processes in bacteria, including production of virulence factors. We characterized anhfqdeletion mutant (Δhfq) ofB. pertussis18323 and show that the Δhfqstrain produces decreased amounts of the adenylate cyclase toxin that plays a central role inB. pertussisvirulence. Production of pertussis toxin and filamentous hemagglutinin was affected to a lesser extent.In vitro, the ability of the Δhfqstrain to survive within macrophages was significantly reduced compared to that of the wild-type (wt) strain. The virulence of the Δhfqstrain in the mouse respiratory model of infection was attenuated, with its capacity to colonize mouse lungs being strongly reduced and its 50% lethal dose value being increased by one order of magnitude over that of the wt strain. In mixed-infection experiments, the Δhfqstrain was then clearly outcompeted by the wt strain. This requirement for Hfq suggests involvement of small noncoding RNA regulation inB. pertussisvirulence.

scholarly journals Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Laura A. Gonyar ◽  
Mary C. Gray ◽  
Gregory J. Christianson ◽  
Borna Mehrad ◽  
Erik L. Hewlett
Keyword(s):  
Adenylate Cyclase ◽  
Whooping Cough ◽  
Critical Factor ◽  
The United States ◽  
Transcriptional Level ◽  
Content Type ◽  
Novel Host ◽  
Fetal Bovine ◽  
Adenylate Cyclase Toxin ◽  
Myeloid Leukocytes

ABSTRACT Pertussis (whooping cough), caused by Bordetella pertussis, is resurging in the United States and worldwide. Adenylate cyclase toxin (ACT) is a critical factor in establishing infection with B. pertussis and acts by specifically inhibiting the response of myeloid leukocytes to the pathogen. We report here that serum components, as discovered during growth in fetal bovine serum (FBS), elicit a robust increase in the amount of ACT, and ≥90% of this ACT is localized to the supernatant, unlike growth without FBS, in which ≥90% is associated with the bacterium. We have found that albumin, in the presence of physiological concentrations of calcium, acts specifically to enhance the amount of ACT and its localization to the supernatant. Respiratory secretions, which contain albumin, promote an increase in amount and localization of active ACT that is comparable to that elicited by serum and albumin. The response to albumin is not mediated through regulation of ACT at the transcriptional level or activation of the Bvg two-component system. As further illustration of the specificity of this phenomenon, serum collected from mice that lack albumin does not stimulate an increase in ACT. These data, demonstrating that albumin and calcium act synergistically in the host environment to increase production and release of ACT, strongly suggest that this phenomenon reflects a novel host-pathogen interaction that is central to infection with B. pertussis and other Bordetella species.

scholarly journals BspR/BtrA, an Anti-σ Factor, Regulates the Ability ofBordetella bronchisepticaTo Cause Cough in Rats

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Keiji Nakamura ◽  
Noriko Shinoda ◽  
Yukihiro Hiramatsu ◽  
Shinya Ohnishi ◽  
Shigeki Kamitani ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Bordetella Pertussis ◽  
Rat Model ◽  
Whooping Cough ◽  
Respiratory Infections ◽  
Wild Type ◽  
Content Type ◽  
Infection Models ◽  
Natural Hosts ◽  
Σ Factor

ABSTRACTBordetella pertussis,B. parapertussis, andB. bronchisepticacause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing afterBordetellainfection. Here, we present a coughing model of rats infected withB. bronchiseptica. Rats, which are one of natural hosts ofB. bronchiseptica, were readily infected with the organisms and showed frequent coughing.B. pertussisalso caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than theB. bronchiseptica-induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection withbspR(btrA)-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from abspR(btrA)-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced byB. bronchisepticain the Bvg+phase. We consider that our rat model provides insight into the pathogenesis of cough induced by theBordetellainfection.IMPORTANCEWhooping cough is a contagious respiratory disease caused byBordetella pertussis. This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzingBordetella-induced coughing is the lack of conventional animal models that replicate coughing. AsBordetella pertussisis highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected withB. bronchiseptica, which shares many virulence factors withB. pertussis. Using this rat model, we demonstrated that some of the major virulence factors ofBordetellaare not involved in cough production, but an anti-σ factor, BspR/BtrA, ofB. bronchisepticaregulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by whichBordetellainduces cough.

Cleft Nucleus Lymphocytosis in Young Infants with Pertussis

2020 ◽  
Author(s):  
Huifang Zhu ◽  
Hongqun Liao ◽  
Xiaoming Zhong ◽  
Xingyu Rao ◽  
Xin Yang ◽  
...  
Keyword(s):  
Young Children ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Pediatric Intensive Care ◽  
Peripheral Blood Smear ◽  
Significant Rise ◽  
Enzyme Linked Immunosorbent Assay ◽  
Respiratory Pathogens ◽  
Pertussis Infection ◽  
Young Infants

AbstractThis study aims to assess whether the cleft nucleus lymphocytosis could be an early promising clue for the diagnosis of pertussis in young infants. Pertussis (whooping cough) is a severe respiratory disease mainly caused by Bordetella pertussis infection and is characterized by a significant rise in the number of leukocyte and lymphocyte in infants and young children. In this study, the Bordetella pertussis DNA was detected from samples of pharyngeal swab by PCR assay. Levels of serum specific IgM against other respiratory pathogens were detected by Enzyme-linked immunosorbent assay (ELISA) assay. The routine blood test including numbers of leukocytes, lymphocytes, and platelets etc. were tested by automatic hemocyte analyzer (Sysemx XN1000). Besides, the morphology of leucocytes was observed in peripheral blood smear with microscope by Wright-Giemsa stain. Three cases of pertussis with cleft nucleus lymphocytes in young infants were discussed in in the neonatal/pediatric intensive care unit in our hospital. Leukocytosis characterized by lymphocytes, as well as thrombocytosis were observed in all patients. Our results demonstrated that cleft nucleus lymphocytosis accompanied with leukocytosis and lymphocytes would be potent assistant indicators for the early diagnosis of pertussis in young children.

scholarly journals Harmonization of Bordetella pertussis Real-Time PCR Diagnostics in the United States in 2012

2014 ◽  
Vol 53 (1) ◽  
pp. 118-123 ◽  
Author(s):  
Margaret M. Williams ◽  
Thomas H. Taylor ◽  
David M. Warshauer ◽  
Monte D. Martin ◽  
Ann M. Valley ◽  
...  
Keyword(s):  
Public Health ◽  
Real Time ◽  
Bordetella Pertussis ◽  
Real Time Pcr ◽  
The United States ◽  
Extraction Methods ◽  
Clinical Samples ◽  
Acid Extraction ◽  
Rt Pcr ◽  
Content Type

Real-time PCR (rt-PCR) is an important diagnostic tool for the identification ofBordetella pertussis,Bordetella holmesii, andBordetella parapertussis. Most U.S. public health laboratories (USPHLs) target IS481, present in 218 to 238 copies in theB. pertussisgenome and 32 to 65 copies inB. holmesii. The CDC developed a multitarget PCR assay to differentiateB. pertussis,B. holmesii, andB. parapertussisand provided protocols and training to 19 USPHLs. The 2012 performance exercise (PE) assessed the capability of USPHLs to detect these threeBordetellaspecies in clinical samples. Laboratories were recruited by the Wisconsin State Proficiency Testing program through the Association of Public Health Laboratories, in partnership with the CDC. Spring and fall PE panels contained 12 samples each of viableBordetellaand non-Bordetellaspecies in saline. Fifty and 53 USPHLs participated in the spring and fall PEs, respectively, using a variety of nucleic acid extraction methods, PCR platforms, and assays. Ninety-six percent and 94% of laboratories targeted IS481in spring and fall, respectively, in either singleplex or multiplex assays. In spring and fall, respectively, 72% and 79% of USPHLs differentiatedB. pertussisandB. holmesiiand 68% and 72% identifiedB. parapertussis. IS481cycle threshold (CT) values forB. pertussissamples had coefficients of variation (CV) ranging from 10% to 28%. Of the USPHLs that differentiatedB. pertussisandB. holmesii, sensitivity was 96% and specificity was 95% for the combined panels. The 2012 PE demonstrated increased harmonization of rt-PCRBordetelladiagnostic protocols in USPHLs compared to that of the previous survey.

scholarly journals Complete Genome Sequence of Bordetella pertussis Pelita III, the Production Strain for an Indonesian Whole-Cell Pertussis Vaccine

2017 ◽  
Vol 5 (17) ◽  
Author(s):  
Yusuf Sofyan Efendi ◽  
Dwi Susanti ◽  
Erman Tritama ◽  
Michelle Lueders Pasier ◽  
Gilang Nadia Niwan Putri ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
World Health ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Whole Cell ◽  
Content Type ◽  
Health Organization ◽  
Production Strain

ABSTRACT PT Bio Farma, the sole World Health Organization-approved Indonesian vaccine producer, manufactures a whole-cell whooping cough vaccine (wP) that, as part of a pentavalent diphtheria-tetanus-pertussis/hepatitis B/Haemophilus influenzae b (DTP/HB/Hib) vaccine, is used in Indonesia and many other countries. We report here the whole-genome sequence for Bordetella pertussis Pelita III, PT Bio Farma’s wP production strain.

scholarly journals Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using aBordetella pertussisChallenge Model in Mice

2018 ◽  
Vol 86 (10) ◽  
Author(s):  
Dylan T. Boehm ◽  
Jesse M. Hall ◽  
Ting Y. Wong ◽  
Andrea M. DiVenere ◽  
Emel Sen-Kilic ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Pertussis Vaccine ◽  
Neutralizing Antibodies ◽  
Protective Antigen ◽  
Whooping Cough ◽  
The United States ◽  
Content Type ◽  
Enhanced Production ◽  
Human Dose ◽  
Antigen Vaccine

ABSTRACTBordetella pertussisis the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor ofB. pertussisthat is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen. The C-terminal repeats-in-toxin domain (RTX) of ACT is sufficient to induce production of toxin-neutralizing antibodies. In this study, we characterized the effectiveness of vaccines containing the RTX antigen against experimental murine infection withB. pertussis. RTX was not protective as a single-antigen vaccine againstB. pertussischallenge, and adding RTX to 1/5 human dose of aP did not enhance protection. Since the doses of aP used in murine studies are not proportionate to mouse/human body masses, we titrated the aP from 1/20 to 1/160 of the human dose. Mice receiving 1/80 human aP dose had bacterial burden comparable to those of naive controls. Adding RTX antigen to the 1/80 aP base resulted in enhanced bacterial clearance. Inclusion of RTX induced production of antibodies recognizing RTX, enhanced production of anti-pertussis toxin, decreased secretion of proinflammatory cytokines, such as interleukin-6, and decreased recruitment of total macrophages in the lung. This study shows that adding RTX antigen to an appropriate dose of aP can enhance protection againstB. pertussischallenge in mice.

Sign in / Sign up

Export Citation Format

Share Document