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Frontiers in Cellular and Infection... 2022A variety of bacteria have evolved the ability to interact with environmental phagocytic predators such as amoebae, which may have facilitated their subsequent...
A variety of bacteria have evolved the ability to interact with environmental phagocytic predators such as amoebae, which may have facilitated their subsequent interactions with phagocytes in animal hosts. Our recent study found that the animal pathogen can evade predation by the common soil amoeba , survive within, and hijack its complex life cycle as a propagation and dissemination vector. However, it is uncertain whether the mechanisms allowing interactions with predatory amoebae are conserved among species, because divergence, evolution, and adaptation to different hosts and ecological niches was accompanied by acquisition and loss of many genes. Here we tested 9 diverse species in three assays representing distinct aspects of their interactions with . Several human and animal pathogens retained the abilities to survive within single-celled amoeba, to inhibit amoebic plaque expansion, and to translocate with amoebae to the fruiting body and disseminate along with the fruiting body. In contrast, these abilities were partly degraded for the bird pathogen , and for the human-restricted species and . Interestingly, a different lineage of only known to infect sheep retained the ability to interact with , demonstrating that these abilities were lost in multiple lineages independently, correlating with niche specialization and recent rapid genome decay apparently mediated by insertion sequences. has been isolated sporadically from diverse human and environmental sources, has acquired insertion sequences, undergone genome decay and has also lost the ability to interact with amoebae, suggesting some specialization to some unknown niche. A genome-wide association study (GWAS) identified a set of genes that are potentially associated with the ability to interact with . These results suggest that massive gene loss associated with specialization of some species to a closed life cycle in a particular host was repeatedly and independently accompanied by loss of the ability to interact with amoebae in an environmental niche.
Topics: Amoeba; Animals; Bordetella; Bordetella bronchiseptica; Dictyostelium; Genome-Wide Association Study; Sheep
PubMed: 35223538
DOI: 10.3389/fcimb.2022.798317 -
Clinical Microbiology and Infection :... Jun 2022To characterize Alcaligenes faecalis metallo-β-lactamase (MBL) AFM-2 and AFM-3 from clinical Pseudomonas aeruginosa isolates NDTH10366, NDTH9845 and WTJH17.
OBJECTIVES
To characterize Alcaligenes faecalis metallo-β-lactamase (MBL) AFM-2 and AFM-3 from clinical Pseudomonas aeruginosa isolates NDTH10366, NDTH9845 and WTJH17.
METHODS
Clinical isolates were whole-genome sequenced using the Illumina and Oxford Nanopore platforms. MICs of clinical isolates and transformants containing MBL genes were determined using broth microdilution methods. Kinetic parameters of purified AFM and NDM-1 were measured using a spectrophotometer. The AFM structure was modelled with SWISS-MODEL.
RESULTS
NDTH10366 and NDTH9845 were extensively drug-resistant (XDR) isolates carrying bla and multiple copies of bla, whereas WTJH17 was an XDR isolate carrying bla. The plasmid-borne bla and bla genes are associated with a novel ISCR element, ISCR29. AFM-2 and AFM-3, differing from AFM-1 by one amino acid substitution each, shared 86.2% and 86.6% amino acid sequence identity with NDM-1, respectively. Phylogenetic analysis confirmed the close relationship between AFM and NDM. Expression of AFM and NDM-1 under their native promoters in DH5α and PAO1 led to elevated MICs for all tested β-lactams except aztreonam. Comparable catalytic abilities were observed for AFM and NDM-1 when hydrolysing nitrocefin, cefepime, imipenem and biapenem, whereas for other tested β-lactams AFM displayed weaker enzymatic activities. Modelling AFM structure revealed a characteristic αβ/βα fold with two zinc-binding active sites.
CONCLUSIONS
AFM from clinical P. aeruginosa isolates demonstrated β-lactamase activity comparable to NDM-1. Co-carriage of bla and bla renders clinical P. aeruginosa isolates non-susceptible to all antipseudomonal β-lactams. The association of bla genes with translocatable genetic elements and plasmids highlights their concerning potential for dissemination.
Topics: Alcaligenes faecalis; Anti-Bacterial Agents; Humans; Microbial Sensitivity Tests; Phylogeny; Pseudomonas Infections; Pseudomonas aeruginosa; beta-Lactamases; beta-Lactams
PubMed: 34826621
DOI: 10.1016/j.cmi.2021.11.012 -
Microbiology Spectrum Apr 2016Since the first description of Bordetella holmesii in 1995, almost 100 publications have contributed to the increasing knowledge of this emerging bacterium. Although... (Review)
Review
Since the first description of Bordetella holmesii in 1995, almost 100 publications have contributed to the increasing knowledge of this emerging bacterium. Although first reported to induce bacteremia mainly in immunocompromised patients, it has also been isolated in healthy persons and has shown the capacity to induce pertussis-like symptoms and other clinical entities, such as meningitis, arthritis, or endocarditis. Respiratory diseases are generally less severe than those induced by Bordetella pertussis. However, B. holmesii was found to have a higher capacity of invasiveness given the various infection sites in which it was isolated. The diagnosis is difficult, particularly as it is a slow-growing organism but also because respiratory infections are systematically misdiagnosed as B. pertussis. Treatment is delicate, as its susceptibility to macrolides (prescribed in respiratory infections) and ceftriaxone (used in invasive disease) is challenged. Regarding prevention, there is no consensus on prophylactic treatment following index cases and no vaccine is available. Epidemiological data are also sparse, with few prevalence studies available. In this chapter, we provide an overview of the current state of knowledge on B. holmesii.
Topics: Bordetella; Bordetella Infections; Ceftriaxone; Humans; Macrolides
PubMed: 27227292
DOI: 10.1128/microbiolspec.EI10-0003-2015 -
Clinical Infectious Diseases : An... Dec 2016
Topics: Bordetella pertussis; Humans; Infections; Th1 Cells; Th17 Cells; Whooping Cough
PubMed: 27838662
DOI: 10.1093/cid/ciw525 -
The Journal of Clinical Investigation Mar 2023BACKGROUNDTo date, only limited data are available on the mechanisms of protection against colonization with Bordetella pertussis in humans.METHODSIn this study, the... (Clinical Trial)
Clinical Trial
BACKGROUNDTo date, only limited data are available on the mechanisms of protection against colonization with Bordetella pertussis in humans.METHODSIn this study, the cellular responses to B. pertussis challenge were monitored longitudinally using high-dimensional EuroFlow-based flow cytometry, allowing quantitative detection of more than 250 different immune cell subsets in the blood of 15 healthy donors.RESULTSParticipants who were protected against colonization showed different early cellular responses compared with colonized participants. Especially prominent for colonization-protected participants were the early expansion of CD36- nonclassical monocytes on day 1 (D1), natural killer cells (D3), follicular T helper cells (D1-D3), and plasma cells (D3). Plasma cell expansion on D3 correlated negatively with the CFU load on D7 and D9 after challenge. Increased plasma cell maturation on D11-D14 was found in participants with seroconversion.CONCLUSIONThese early cellular immune responses following experimental infection can now be further characterized and potentially linked to an efficient mucosal immune response, preventing colonization. Ultimately, their presence may be used to evaluate whether new B. pertussis vaccine candidates are protective against B. pertussis colonization, e.g., by bacterial challenge after vaccination.TRIAL REGISTRATIONClinicalTrials.gov NCT03751514.FUNDINGInnovative Medicines Initiative 2 Joint Undertaking and the EuroFlow Consortium.
Topics: Humans; Bordetella pertussis; Kinetics; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 36649086
DOI: 10.1172/JCI163121 -
Cell Reports Aug 2023How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical...
How the opportunistic Gram-negative pathogens of the genus Achromobacter interact with the innate immune system is poorly understood. Using three Achromobacter clinical isolates from two species, we show that the type 3 secretion system (T3SS) is required to induce cell death in human macrophages by inflammasome-dependent pyroptosis. Macrophages deficient in the inflammasome sensors NLRC4 or NLRP3 undergo pyroptosis upon bacterial internalization, but those deficient in both NLRC4 and NLRP3 do not, suggesting either sensor mediates pyroptosis in a T3SS-dependent manner. Detailed analysis of the intracellular trafficking of one isolate indicates that the intracellular bacteria reside in a late phagolysosome. Using an intranasal mouse infection model, we observe that Achromobacter damages lung structure and causes severe illness, contingent on a functional T3SS. Together, we demonstrate that Achromobacter species can survive phagocytosis by promoting macrophage cell death and inflammation by redundant mechanisms of pyroptosis induction in a T3SS-dependent manner.
Topics: Humans; Animals; Mice; Pyroptosis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Type III Secretion Systems; Achromobacter; Disease Models, Animal; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins
PubMed: 37598340
DOI: 10.1016/j.celrep.2023.113012 -
Toxins Feb 2023As a tribute to Louis Pasteur on the occasion of the 200th anniversary of his birth, this article summarizes the main contributions of scientists from Pasteur Institutes... (Review)
Review
As a tribute to Louis Pasteur on the occasion of the 200th anniversary of his birth, this article summarizes the main contributions of scientists from Pasteur Institutes to the current knowledge of toxins produced by . The article therefore focuses on publications authored by researchers from Pasteur Institutes and is not intended as a systematic review of toxins. Besides identifying as the causative agent of whooping cough, Pasteurians have made several major contributions with respect to the structure-function relationship of the lipo-oligosaccharide, adenylyl cyclase toxin and pertussis toxin. In addition to contributing to the understanding of these toxins' mechanisms at the molecular and cellular levels and their role in pathogenesis, scientists at Pasteur Institutes have also exploited potential applications of the gathered knowledge of these toxins. These applications range from the development of novel tools to study protein-protein interactions over the design of novel antigen delivery tools, such as prophylactic or therapeutic vaccine candidates against cancer and viral infection, to the development of a live attenuated nasal pertussis vaccine. This scientific journey from basic science to applications in the field of human health matches perfectly with the overall scientific objectives outlined by Louis Pasteur himself.
Topics: Humans; Bordetella pertussis; Whooping Cough; Pertussis Toxin; Virulence Factors, Bordetella; Adenylate Cyclase Toxin; Pertussis Vaccine
PubMed: 36977067
DOI: 10.3390/toxins15030176 -
Chest Aug 2017Pertussis (whooping cough) is a highly infective cause of cough that causes significant morbidity and mortality. Existing case definitions include paroxysmal cough,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pertussis (whooping cough) is a highly infective cause of cough that causes significant morbidity and mortality. Existing case definitions include paroxysmal cough, whooping, and posttussive vomiting, but diagnosis can be difficult. We determined the diagnostic accuracy of clinical characteristics of pertussis-associated cough.
METHODS
We systematically searched CINAHL, Embase, Medline, and SCI-EXPANDED/CPCI-S up to June 2016. Eligible studies compared clinical characteristics in those positive and negative for Bordetella pertussis infection, confirmed by laboratory investigations. Two authors independently completed screening, data extraction, and quality and bias assessments. For each characteristic, RevMan was used to produce descriptive forest plots. The bivariate meta-analysis method was used to generate pooled estimates of sensitivity and specificity.
RESULTS
Of 1,969 identified papers, 53 were included. Forty-one clinical characteristics were assessed for diagnostic accuracy. In adult patients, paroxysmal cough and absence of fever have a high sensitivity (93.2% [CI, 83.2-97.4] and 81.8% [CI, 72.2-88.7], respectively) and low specificity (20.6% [CI, 14.7-28.1] and 18.8% [CI, 8.1-37.9]), whereas posttussive vomiting and whooping have low sensitivity (32.5% [CI, 24.5-41.6] and 29.8% [CI, 8.0-45.2]) and high specificity (77.7% [CI, 73.1-81.7] and 79.5% [CI, 69.4-86.9]). Posttussive vomiting in children is moderately sensitive (60.0% [CI, 40.3-77.0]) and specific (66.0% [CI, 52.5-77.3]).
CONCLUSIONS
In adult patients, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children, posttussive vomiting is much less helpful as a clinical diagnostic test.
Topics: Adult; Bordetella pertussis; Child; Cough; Diagnosis, Differential; Humans; Whooping Cough
PubMed: 28511929
DOI: 10.1016/j.chest.2017.04.186 -
Central European Journal of Public... Dec 2022The aim of the study was to investigate possible emergence of resistance to disinfectants in Bordetella pertussis strains isolated from patients with whooping cough in...
OBJECTIVES
The aim of the study was to investigate possible emergence of resistance to disinfectants in Bordetella pertussis strains isolated from patients with whooping cough in the Czech Republic in 2014 and 2015.
METHODS
In an EN1500-based study, clean and dry fingertips of volunteers were always contaminated with one of the two clinical isolates of B. pertussis. Clinical isolates of B. pertussis were obtained from the National Reference Laboratory for Pertussis and Diphtheria, National Institute of Public Health (NIPH), Prague, Czech Republic. Dry and contaminated fingertips were immersed in 10 ml medium and then rubbed with the fingers for 1 minute. After that, the hands were treated with isopropanol 60% v/v or tested products, and then the fingertips were rubbed again into 10 ml of pure medium for 1 minute. The suspensions obtained were immediately diluted and plated on charcoal medium.
RESULTS
Ethanol-based product A and propanol-based product B showed bactericidal activity after 30 s of contact. The confidence interval limit for product A and B was 0.12 and 0.19, respectively. Quaternary ammonium compound-based product C was found to be ineffective after 30 s of contact. The confidence interval limit for product C was 0.62.
CONCLUSION
Products A and B were assessed as effective against clinical isolates of B. pertussis in accordance with EN 1500. Quaternary ammonium compound-based product C did not comply with the requirements of EN 1500.
Topics: Humans; Bordetella pertussis; Whooping Cough; Hand Sanitizers; Quaternary Ammonium Compounds; Czech Republic
PubMed: 36718925
DOI: 10.21101/cejph.a7141 -
Toxins Jul 2018The adenylate cyclase toxin (CyaA) is one of the major virulence factors of , the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon... (Review)
Review
The adenylate cyclase toxin (CyaA) is one of the major virulence factors of , the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon activation by endogenous calmodulin, it synthesizes massive amounts of cAMP that alters cellular physiology. The CyaA toxin is a 1706 residues-long bifunctional protein: the catalytic domain is located in the 400 amino-proximal residues, whereas the carboxy-terminal 1306 residues are implicated in toxin binding to the cellular receptor, the αβ₂ (CD11b/CD18) integrin, and subsequently in the translocation of the catalytic domain across the cytoplasmic membrane of the target cells. Indeed, this protein is endowed with the unique capability of delivering its N-terminal catalytic domain directly across the plasma membrane of eukaryotic target cells. These properties have been exploited to engineer the CyaA toxin as a potent non-replicating vector able to deliver antigens into antigen presenting cells and elicit specific cell-mediated immune responses. Antigens of interest can be inserted into the CyaA protein to yield recombinant molecules that are targeted in vivo to dendritic cells, where the antigens are processed and presented by the major class I and class II histocompatibility complexes (MHC-I and II). CyaA turned out to be a remarkably effective and versatile vaccine vector capable of inducing all the components of the immune response (T-CD4, T-CD8, and antibody). In this chapter, we summarize the basic knowledge on the adenylate cyclase toxin and then describe the application of CyaA in vaccinology, including some recent results of clinical trials of immunotherapy using a recombinant CyaA vaccine.
Topics: Adenylate Cyclase Toxin; Animals; Antigens; Bioengineering; Bordetella pertussis; Humans; Immunotherapy
PubMed: 30037010
DOI: 10.3390/toxins10070302