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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 -
Proceedings of the National Academy of... Oct 2023The pathogenic bacteria and cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We...
The pathogenic bacteria and cause pertussis (whooping cough) and pertussis-like disease, respectively, both of which are characterized by paroxysmal coughing. We previously reported that pertussis toxin (PTx), which inactivates heterotrimeric GTPases of the G family through ADP-ribosylation of their α subunits, causes coughing in combination with Vag8 and lipid A in infection. In contrast, the mechanism of cough induced by , which produces Vag8 and lipopolysaccharide (LPS) containing lipid A, but not PTx, remained to be elucidated. Here, we show that a toxin we named deacylating autotransporter toxin (DAT) of inactivates heterotrimeric G GTPases through demyristoylation of their α subunits and contributes to cough production along with Vag8 and LPS. These results indicate that DAT plays a role in infection in place of PTx.
Topics: Humans; Bordetella parapertussis; Whooping Cough; Type V Secretion Systems; Cough; Lipid A; Lipopolysaccharides; Bordetella pertussis; Pertussis Toxin; Toxins, Biological
PubMed: 37748060
DOI: 10.1073/pnas.2308260120 -
Emerging Microbes & Infections Dec 2023causes pertussis (or whooping cough), a severe respiratory infectious disease in infants, although it can be prevented by whole cell and acellular vaccines. The recent...
causes pertussis (or whooping cough), a severe respiratory infectious disease in infants, although it can be prevented by whole cell and acellular vaccines. The recent pertussis resurgence in industrialised countries is partly attributed to pathogen adaptation to vaccines, while emergence of antimicrobial resistance, specifically to macrolides in China, has become a concern. Surveillance of current circulating and emerging strains is therefore vital to understand the risks they pose to public health. Although the use of genomics-based typing is increasing a genomic nomenclature for this pathogen has not been well established. Here, we implemented the multilevel genome typing (MGT) system for with five levels of resolution, which provide targeted typing of relevant lineages and discrimination of closely related strains at the finest scale. The lower resolution levels (MGT2 and MGT3) describe the distribution of major vaccine antigen alleles including , and as well as temporal and spatial trends within the global population. Mid-resolution levels (MGT3 and MGT4) enable typing of antibiotic-resistant lineages and Prn deficient lineages within the clade. The high-resolution level (MGT5) can capture finer-scale epidemiology such as outbreaks and local transmission events, with comparable resolution to existing genomic methods of strain-relatedness assessment. The scheme offers stable MGT-type assignments aiding harmonisation of typing and communication between laboratories. The scheme is available at https://mgtdb.unsw.edu.au/pertussis, is regularly updated from global data repositories and accepts public submissions. The MGT scheme provides a comprehensive, robust, and scalable system for global surveillance of .
Topics: Infant; Humans; Bordetella pertussis; Whooping Cough; Pertussis Vaccine; Genomics; Whole Genome Sequencing
PubMed: 37483082
DOI: 10.1080/22221751.2023.2239945 -
Antimicrobial Agents and Chemotherapy Jul 2023We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for...
We conducted antimicrobial susceptibility testing of 267 isolates for 16 antibiotics from 2017 to 2022. The highest susceptibility was found for piperacillin-tazobactam (70%) and ceftazidime-avibactam (62%). Between 30% and 49% of strains were susceptible to tigecycline, ceftazidime, and meropenem. We applied species-specific Achromobacter xylosoxidans breakpoints for piperacillin-tazobactam, meropenem, and trimethoprim-sulfamethoxazole and EUCAST pharmacokinetic/pharmacodynamic (PK/PD) breakpoints for the others. A. xylosoxidans was the most frequently isolated species, followed by Achromobacter insuavis and Achromobacter ruhlandii.
Topics: Humans; Meropenem; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Achromobacter; Piperacillin; Tazobactam
PubMed: 37310234
DOI: 10.1128/aac.00379-23 -
Nature Communications Dec 2022Bordetella pertussis (Bp), the causative agent of pertussis, continues to circulate despite widespread vaccination programs. An important question is whether and how...
Bordetella pertussis (Bp), the causative agent of pertussis, continues to circulate despite widespread vaccination programs. An important question is whether and how (sub)clinical infections shape immune memory to Bp, particularly in populations primed with acellular pertussis vaccines (aP). Here, we examine the prevalence of mucosal antibodies against non-vaccine antigens in aP-primed children and adolescents of the BERT study (NCT03697798), using antibody binding to a Bp mutant strain lacking aP antigens (Bp_mut). Our study identifies increased levels of mucosal IgG and IgA binding to Bp_mut in older aP-primed individuals, suggesting different Bp exposure between aP-primed birth cohorts, in line with pertussis disease incidence data. To examine whether Bp exposure influences vaccination responses, we measured mucosal antibody responses to aP booster vaccination as a secondary study outcome. Although booster vaccination induces significant increases in mucosal antibodies to Bp in both cohorts, the older age group that had higher baseline antibodies to Bp_ mut shows increased persistence of antibodies after vaccination.
Topics: Adolescent; Child; Humans; Antibodies; Antibody Formation; Antigens, Bacterial; Bordetella pertussis; Immunization, Secondary; Vaccination; Whooping Cough
PubMed: 36460655
DOI: 10.1038/s41467-022-35165-w -
Microbiological Research Oct 2022Bacteria belonging to the genus Achromobacter are widely distributed in natural environments and have been recognized as emerging pathogens for their contribution to a... (Review)
Review
Bacteria belonging to the genus Achromobacter are widely distributed in natural environments and have been recognized as emerging pathogens for their contribution to a wide range of human infections. In particular, patients with cystic fibrosis (CF) are the subjects most frequently colonized by Achromobacter spp., which can cause persistent infections in their respiratory tract. Although many clinical aspects and pathogenic mechanisms still remain to be elucidated, Achromobacter spp. have been a source of expanding interest in recent years. This review examines the current literature regarding Achromobacter spp. role in CF, focusing on taxonomy, prevalence in CF lung infections, genomic characteristics, and adaptation strategies including modifications of metabolism and virulence, acquisition of antibiotic resistance, exchange of mobile genetic elements and development of hypermutation.
Topics: Achromobacter; Achromobacter denitrificans; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Prevalence
PubMed: 35931003
DOI: 10.1016/j.micres.2022.127140 -
Microbiology Spectrum Apr 2022Achromobacter denitrificans is an environmental opportunistic pathogen that is infecting a large number of immunocompromised patients. A more recently identified strain...
Achromobacter denitrificans is an environmental opportunistic pathogen that is infecting a large number of immunocompromised patients. A more recently identified strain from the historical collection of strains of Achromobacter denitrificans is Achromobacter mucicolens. In hosts with a variety of underlying diseases, spp. can induce a wide spectrum of disorders. Because of the bacterium's intrinsic genetic constitution and resistance gained over time, antibiotics are challenged to handle Due to the fact that is rare and its taxonomy is not completely understood, it is difficult to define clinical symptoms, acquisition risk factors, and thus the best therapeutic course of action. To help comprehend this intrinsic and acquired resistance, we analyzed the entire genome of the strain and utilized bioinformatics methods to estimate the strain's probable drug resistance profile. In our study, we have isolated and cultured a clinically important strain and subjected it to antimicrobial susceptibility tests against antibiotics in the Vitek 2 testing system. The strain's genome sequence as well as an investigation of 27 of its phenotypic traits provides important information regarding this pathogen. The genome of this strain possesses a number of antibiotic resistance genes that code for efflux pump systems and other antibiotic-regulating as well as -modifying enzymes. Our research analysis predicted genes involved in drug resistance, including genes for efflux pump systems, antibiotic efflux, antibiotic inactivation, and antibiotic target alteration. studies validated the genomic evidence for its ability to exhibit resistance against a wide range of antibiotics. Our investigation paves the way for more research on understanding the functioning of the key discovered genes that contribute toward the pathogenicity of and hence gives new information and treatment options for this emerging pathogen. species are well-known opportunistic human pathogens that can be found in water and soil and most commonly in hospital settings. They thrive in immunocompromised individuals, producing sporadic cases of pneumonia, septicemia, peritonitis, urinary tract infections, and other illnesses. strains are inherently resistant to a wide spectrum of antibiotics, making them difficult to treat promptly. The strain under study, , was notably resistant to various antibiotics, and the infection could be controlled only after several rounds of prescription medications at different doses. This consumed a lot of time and put the already immunosuppressed leukemic patient through a great ordeal. The study aimed to raise awareness about the importance of the bacterium's lethality, and doctors should evaluate the bacterium's potential for resistance before prescribing antibiotics. Sanitation and other precautions should also be implemented in hospitals and other public places.
Topics: Achromobacter; Achromobacter denitrificans; Anti-Bacterial Agents; Drug Resistance, Microbial; Genomics; Humans; Microbial Sensitivity Tests
PubMed: 35377213
DOI: 10.1128/spectrum.01916-21