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Scientific Reports May 2023Autoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown....
Autoagglutination (Agg) of Bordetella pertussis is often observed in clinical laboratory. However, its causal factors and frequency in circulating strains are unknown. Repeated single colony isolation enabled us to detect an Agg mutant in the supernatant of an Agg strain of B. pertussis. Whole-genome sequencing and immunoblot analysis disclosed that the Agg mutant had a single C-deletion in its fim3 promoter region (Pfim3) which abolished Fim3 fimbriae production. A B. pertussis fim3-knock out mutant also lacked the Agg phenotype. Agg clinical isolates were detected a higher production of Fim3 than Fim3-producing Agg isolates. B. pertussis is known to harbor multiple Pfim3 poly(C) lengths within a single strain culture and our newly developed PCR/LDR assay revealed that Agg isolates harbor the highest Pfim3 poly-14C abundance. We evaluated the frequency of autoagglutination in clinical B. pertussis isolates collected in Japan between 1994 and 2018 (n = 203). Fim3 production was confirmed for 190 isolates and 74.7% of them displayed the Agg phenotype. The Agg phenotype was strongly associated with Pfim3 poly-14C abundance. Taken together, our findings demonstrated that B. pertussis autoagglutination occurs in response to high Fim3 levels and the Agg strain has predominated in Japan over the past two decades.
Topics: Humans; Bordetella pertussis; Whooping Cough; Fimbriae, Bacterial; Phenotype; Pertussis Vaccine
PubMed: 37165008
DOI: 10.1038/s41598-023-34672-0 -
Pathogens and Disease Feb 2016Bordetella bronchiseptica and B. pertussis are Gram-negative bacteria that cause respiratory diseases in animals and humans. The current incidence of whooping cough or... (Review)
Review
Bordetella bronchiseptica and B. pertussis are Gram-negative bacteria that cause respiratory diseases in animals and humans. The current incidence of whooping cough or pertussis caused by B. pertussis has reached levels not observed since the 1950s. Although pertussis is traditionally known as an acute childhood disease, it has recently resurged in vaccinated adolescents and adults. These individuals often become silent carriers, facilitating bacterial circulation and transmission. Similarly, vaccinated and non-vaccinated animals continue to be carriers of B. bronchiseptica and shed bacteria resulting in disease outbreaks. The persistence mechanisms of these bacteria remain poorly characterized. It has been proposed that adoption of a biofilm lifestyle allows persistent colonization of the mammalian respiratory tract. The history of Bordetella biofilm research is only a decade long and there is no single review article that has exclusively focused on this area. We systematically discuss the role of Bordetella factors in biofilm development in vitro and in the mouse respiratory tract. We further outline the implications of biofilms to bacterial persistence and transmission in humans and for the design of new acellular pertussis vaccines.
Topics: Animals; Biofilms; Bordetella Infections; Bordetella bronchiseptica; Bordetella pertussis; Carrier State; Disease Outbreaks; Humans
PubMed: 26586694
DOI: 10.1093/femspd/ftv108 -
Frontiers in Bioscience (Landmark... Dec 2021In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the... (Review)
Review
In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the past, the most important health problem that has significantly reduced the quality of life in CF patients is the progressive deterioration of lung structure and function. In recent years, Achromobacter species have emerged with increasing incidence in the respiratory secretions of CF subjects. The significance of this detection remains debated. In this review article, the characteristics of these pathogens, the importance of their presence in CF patients, and possible antibiotic treatment of treatments for colonization and infection are discussed. Literature analysis shows that Achromobacter species, mainly A. xylosoxidans, are pathogens with intrinsic characteristics that favour persistent lung colonization and several virulence factors and secretion systems that significantly interfere with respiratory cell survival. However, although it seems undebatable that Achromobacterspecies detection is a marker of CF severity, the role of these pathogens as a cause of lung structure and functional deterioration is not definitively established. Nonetheless, there is general agreement about the need for antibiotic therapy to eradicate these pathogens when they are detected in CF patients. Unfortunately, eradication is difficult, and no standard treatment is recommended by scientific societies. New possibilities are potentially offered by some recently developed drugs, such as cefiderocol, but further studies on the dosage, treatment duration and efficacy and safety of this new antibiotic in CF patients of different ages are urgently needed.
Topics: Achromobacter; Anti-Bacterial Agents; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Quality of Life
PubMed: 34994175
DOI: 10.52586/5054 -
Applied and Environmental Microbiology Nov 2021In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed...
In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed that this is located adjacent to an gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite [MAs(III)], the organoarsenic compound roxarsone(III) [Rox(III)], and the inorganic antimonite [Sb(III)]. Similar genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarR. MarR orthologs have three conserved cysteine residues, which are Cys36, Cys37, and Cys157 in sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarR (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that is expressed constitutively in a deletion mutant, indicating that represses transcription of . Moreover, electrophoretic mobility shift assays (EMSAs) demonstrate that AdMarR binds to the promoters of both and in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarR is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of which confers resistance to MAs(III), Rox(III), and Sb(III). AdMarR and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics. In this study, a MarR family member, AdMarR was shown to regulate the gene, which confers resistance to arsenic-containing antibiotics. It is a founding member of a distinct subfamily that we refer to as MarR, regulating genes conferring resistance to arsenic and antimony antibiotic compounds. AdMarR was shown to be a repressor containing conserved cysteine residues that are required to bind As(III) and Sb(III), leading to a conformational change and subsequent derepression. Here we show that members of the MarR family are involved in regulating arsenic-containing compounds.
Topics: Achromobacter; Anti-Bacterial Agents; Arsenic; Arsenicals; Cysteine; Drug Resistance, Bacterial; Genes, Bacterial; Multigene Family; Phylogeny; Roxarsone
PubMed: 34613763
DOI: 10.1128/AEM.01588-21 -
Microbial Genomics Dec 2023Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32...
Pertussis remains a public health concern in South Africa, with an increase in reported cases and outbreaks in recent years. Whole genome sequencing was performed on 32 isolates sourced from three different surveillance programmes in South Africa between 2015 and 2019. Genome sequences were characterized using multilocus sequence typing, vaccine antigen genes (, , , and ) and overall genome structure. All isolates were sequence type 2 and harboured the pertussis toxin promoter allele . The dominant genotype was 3122 (31/32, 96.9 %), with no pertactin-deficient or other mutations in vaccine antigen genes identified. Amongst 21 isolates yielding closed genome assemblies, eight distinct genome structures were detected, with 61.9 % (13/21) of the isolates exhibiting three predominant structures. Increases in case numbers are probably not due to evolutionary changes in the genome but possibly due to other factors such as the cyclical nature of disease, waning immunity due to the use of acellular vaccines and/or population immunity gaps.
Topics: Humans; Bordetella pertussis; Whooping Cough; South Africa; Pertussis Vaccine; Genomics
PubMed: 38117675
DOI: 10.1099/mgen.0.001162 -
Emerging Infectious Diseases May 2024To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities...
To determine changes in Bordetella pertussis and B. parapertussis detection rates, we analyzed 1.43 million respiratory multiplex PCR test results from US facilities from 2019 through mid-2023. From mid-2022 through mid-2023, Bordetella spp. detection increased 8.5-fold; 95% of detections were B. parapertussis. While B. parapertussis rates increased, B. pertussis rates decreased.
Topics: Bordetella parapertussis; United States; Humans; Bordetella Infections; Communicable Diseases, Emerging; Bordetella pertussis; History, 21st Century; Child; Child, Preschool; Whooping Cough; Adult; Adolescent; Infant; Multiplex Polymerase Chain Reaction; Young Adult
PubMed: 38666607
DOI: 10.3201/eid3005.231278 -
Applied Microbiology and Biotechnology Feb 2022Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an... (Review)
Review
Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an evolution of concerns with acellular component vaccination have both sparked a renewed interest. Although simian models of infection best correlate with the observed attributes of human infection, several animal models have been used for decades and have positively contributed in many ways to the related science. Nevertheless, there is yet the lack of a reliable small animal model system that mimics the combination of infection genesis, variable upper and lower respiratory infection, systemic effects, infection resolution, and vaccine responses. This narrative review examines the history and attributes of non-primate animal models for pertussis and places context with the current use and needs. Emerging from the latter is the necessity for further such study to better create the optimal model of infection and vaccination with use of current molecular tools and a broader range of animal systems. KEY POINTS: • Currently used and past non-primate animal models of B. pertussis infection often have unique and focused applications. • A non-primate animal model that consistently mimics human pertussis for the majority of key infection characteristics is lacking. • There remains ample opportunity for an improved non-primate animal model of pertussis with the use of current molecular biology tools and with further exploration of species not previously considered.
Topics: Animals; Bordetella pertussis; Disease Models, Animal; Humans; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 35103810
DOI: 10.1007/s00253-022-11798-1 -
Frontiers in Immunology 2023Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular...
Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces nasal colonization.
INTRODUCTION
Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular pertussis vaccines (aPV) delivered intramuscularly reduce bacterial numbers in the lungs of immunized animals and humans, but do not reduce nasal colonization. Thus, aPV-immunized individuals are sources of community transmission. We showed previously that modification of a commercial aPV (Boostrix) by addition of the Th1/17 polarizing adjuvant Bordetella Colonization Factor A (BcfA) attenuated Th2 responses elicited by alum and accelerated clearance of B. pertussis from mouse lungs. Here we tested whether a heterologous immunization strategy with systemic priming and mucosal booster (prime-pull) would reduce nasal colonization.
METHODS
Adult male and female mice were immunized intramuscularly (i.m.) with aPV or aPV/BcfA and boosted either i.m. or intranasally (i.n.) with the same formulation. Tissue-resident memory (TRM) responses in the respiratory tract were quantified by flow cytometry, and mucosal and systemic antibodies were quantified by ELISA. Immunized and naïve mice were challenged i.n. with Bordetella pertussis and bacterial load in the nose and lungs enumerated at days 1-14 post-challenge.
RESULTS
We show that prime-pull immunization with Boostrix plus BcfA (aPV/BcfA) generated IFNγ+ and IL-17+ CD4+ lung resident memory T cells (TRM), and CD4+IL-17+ TRM in the nose. In contrast, aPV alone delivered by the same route generated IL-5+ CD4+ resident memory T cells in the lungs and nose. Importantly, nasal colonization was only reduced in mice immunized with aPV/BcfA by the prime-pull regimen.
CONCLUSIONS
These results suggest that TH17 polarized TRM generated by aPV/BcfA may reduce nasal colonization thereby preventing pertussis transmission and subsequent resurgence.
Topics: Animals; Female; Male; Mice; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Bordetella pertussis; CD4-Positive T-Lymphocytes; Interleukin-17; Pertussis Vaccine; Whooping Cough
PubMed: 37275891
DOI: 10.3389/fimmu.2023.1181876 -
Frontiers in Cellular and Infection... 2020Pertussis, also known as whooping cough, is a resurging acute respiratory disease of humans primarily caused by the Gram-negative coccobacilli , and less commonly by the... (Review)
Review
Pertussis, also known as whooping cough, is a resurging acute respiratory disease of humans primarily caused by the Gram-negative coccobacilli , and less commonly by the human-adapted lineage of . The ovine-adapted lineage of infects only sheep, while causes chronic and often asymptomatic respiratory infections in a broad range of mammals but rarely in humans. A largely overlapping set of virulence factors inflicts the pathogenicity of these bordetellae. Their genomes also harbor a pathogenicity island, named locus, that encodes components of the type III secretion injectosome, and adjacent locus with the type III regulatory proteins. The Bsc injectosome of bordetellae translocates the cytotoxic BteA effector protein, also referred to as BopC, into the cells of the mammalian hosts. While the role of type III secretion activity in the persistent colonization of the lower respiratory tract by is well recognized, the functionality of the type III secretion injectosome in was overlooked for many years due to the adaptation of laboratory-passaged strains. This review highlights the current knowledge of the type III secretion system in the so-called classical species, comprising , and , and discusses its functional divergence. Comparison with other well-studied bacterial injectosomes, regulation of the type III secretion on the transcriptional and post-transcriptional level, and activities of BteA effector protein and BopN protein, homologous to the type III secretion gatekeepers, are addressed.
Topics: Animals; Bacterial Proteins; Bordetella Infections; Bordetella bronchiseptica; Bordetella pertussis; Sheep; Type III Secretion Systems; Virulence Factors
PubMed: 33014891
DOI: 10.3389/fcimb.2020.00466 -
Viruses Jul 2023species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced...
species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced fatal exacerbations. spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of . In this study, thirteen lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Kumeyaay phage collection. Six distinct phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 10 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.
Topics: Adult; Humans; Bacteriophages; Cystic Fibrosis; Phylogeny; Achromobacter; Achromobacter denitrificans; Prophages; Endotoxins
PubMed: 37632008
DOI: 10.3390/v15081665