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PubMed1978

[Protection against infection with Bordetella pertussis by an oligopeptide from Bordetella pertussis (author's transl)].

We have isolated from Bordetella pertussis an oligopeptide with characteristic amino acid composition. This peptide was applied to mice in standardized tests for pertussis immunization. In three tests with three independent isolates of peptide, a significant and dose dependent protection was observed. One microgram of peptide per mouse produces the same protective effect as 0.1 IU of pertussis vaccine. It is important to note that similar peptides can be isolated from other bacteria and other DNA containing cellular organisms which have specific amino acid compositions and which are antigens specific for the organism from which they were isolated. The antigens are very potent, e.g., one ng of Mycobacterium tuberculosis peptide is equivalent to one unit of tuberculin. It is conceivable that immunizing effects such as those observed for pertussis are common to the peptides of this group. Since all such peptides are isolated from a group of low molecular weight ribonucleoproteins, as first reported by WILHELM, we propose the term nucleopeptides for this group. Oligopeptides of the nucleopeptide group are now available for sequence analysis. We expect that synthetic peptides of this group will become available in time for diagnosis, prophylaxis and therapy of a number of diseases.

Animals↗

PubMed2026

Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study.

BACKGROUND: Bordetella pertussis continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant B pertussis strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global B pertussis diagnostic capability and genomic surveillance. METHODS: We did a nationwide genomic epidemiology study of B pertussis RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant B pertussis-specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant B pertussis genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated. FINDINGS: 255 respiratory specimens positive for B pertussis were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete B pertussis genomes through tNGS. Seven co-circulating lineages of B pertussis were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant B pertussis with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for B pertussis was 4% (eight of 188). INTERPRETATION: tNGS can recover near-complete B pertussis genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow. FUNDING: NSW Health Prevention Research Support Program.

Macrolides↗

PubMed2025

Proteomic comparison of epidemic Australian Bordetella pertussis biofilm cells.

Bordetella pertussis causes whooping cough, a severe respiratory infectious disease. Studies have compared the currently dominant single nucleotide polymorphism (SNP) cluster I (pertussis toxin promoter allele, ptxP3) and previously dominant SNP cluster II (ptxP1) strains as planktonic cells. Since biofilm formation is linked with B. pertussis pathogenesis in vivo, this study compared the biofilm formation capabilities of representative strains of cluster I and cluster II. Confocal laser scanning microscopy found that the cluster I strain had a denser biofilm structure compared to the cluster II strain. Differences in protein abundance of the biofilm cells were then compared using tandem mass tagging and high-resolution multiple reaction monitoring. In total, 1,453 proteins were identified, of which 40 proteins had significant differential abundance between the two strains in biofilm conditions. Of particular interest was a large increase in the abundance of energy metabolism proteins (cytochrome proteins PetABC and BP3650) in the cluster I strain. When the abundance of these proteins was compared between six additional strains from each cluster, it was found that the protein abundance varied between all strains. These findings suggest that there are large levels of individual proteomic diversity between B. pertussis strains in biofilm conditions despite the highly conserved genome of the species. Overall, this study revealed visual differences in biofilm structure between B. pertussis strains and highlighted strain-specific variation in protein abundance that dominates potential cluster-specific changes that may be linked with the dominance of cluster I strains.IMPORTANCEBordetella pertussis causes whooping cough. The currently circulating cluster I strains have taken over previously dominant cluster II strains. It is important to understand the reasons behind this evolution to develop new strategies against the pathogen. Recent studies have shown that B. pertussis can form biofilms during infection. This study compared the biofilm formation capabilities of a cluster I and a cluster II strain and identified visual differences in the biofilms. The protein abundance between these strains grown in biofilms was compared, and proteins identified with varied abundance were measured with additional strains from each cluster. It was found that despite the highly conserved genetics of the species, there was varied protein abundance between the additional strains. This study highlights that strain-specific variation in protein abundance during biofilm conditions may dominate the cluster-specific changes that may be linked to the dominance of cluster I strains.

Bordetella pertussis↗

PubMed1976

The effect of pertussis and beta adrenergic-blocking agents on mast cells.

Pertussis vaccine injected ip in doses known to cause hypersensitization resulted in a marked decrease in the number of mast cells from the peritoneal washings of rats and mice. A significant reduction was obtained as early as one day after pertussis injection of ten billion cells in rats and was marked after 5 to 7 days. A maximum reduction in the number of mast cells was obtained by a dose of 20 billion cells. There was no detectable histamine biological activity in the supernatant from peritoneal washings obtained after 10 min, 60 min, and 24 hr from control and pertussis-treated rats, indicating that pertussis did not cause degranulation of mast cells in vivo. The histamine content in the precipitated mast cell pellets from control rats was much higher than the corresponding histamine content from pertussis-treated rats. In rats and mice, propranolol and other beta adrenergic-blocking agents caused degranulation of mast cells in the peritoneal washings in vitro. Practolol was the least effective beta adrenergic-blocking agent in degranulating mast cells. Catecholamines, histamine, 6-hydroxydopamine, methacholine, and pertussis failed to cause any degranulation. Isoproterenol protected the mast cell against the degranulation induced by propranolol. Propranolol caused bluing in rat and mice skin when injected id. Mast cells from control and pertussis-injected rats were equally sensitive to propranolol in vitro. The low recovery of mast cells from the peritoneal washings of rats and mice is thought to be due to mobilization of mast cells away from the peritoneum.

Adrenergic beta-Antagonists↗

PubMed1975

Use of pertussis vaccine in an epidemic involving hospital staff.

An epidemic of pertussis occurred among hospital staff caring for paediatric patients. Eight physicians and five nurses were affected. Pertussis developed in six newborn infants exposed to infected hospital staff in the nursery. Erythromycin prophylaxis was used to control the epidemic. Clinical pertussis developed in five adults infected with Bordetella pertussis before erythromycin was used, whereas symptoms developed in only one of the eight adults who became infected after erythromycin prophylaxis was started. Pertussis vaccine was given to adult volunteers in the hospital, and in 77% of two hundred and eighty-six vaccinees there was a fourfold rise in pertussis agglutinins. Local reactions were common, and in two vaccinees generalised rashes developed. One of these required treatment with corticosteroids. The risk of pertussis occurring in adults providing medical care for children should be recognised, and employees with symptoms should be removed from the hospital environment.

Adolescent↗

PubMed1976

The effects of Bordetella pertussis vaccine on cerebral vascular permeability.

The effect of Bordetella pertussis vaccine on the cerebral vascular permeability in the mouse was studied by a radio-isotope method (131I-labelled HSA). Intravenous injection of 4 x 1010 heat-killed pertussis organisms caused a measurable increase in permeability in normal mice. Cryoinjury to the cerebral hemispheres resulted in a striking increase in vascular permeability at 24 h. This declined within 48 h and stabilized at a level fractionally higher than normal at 7 days ("healed lesion"). When pertussis organisms were injected into mice bearing ("healed lesion"). When pertussis organisms were injected into mice bearing "healed lesions" the increase in permeability was similar in magnitude to that in uninjured brain. The effect was increased by a second administration of pertussis 24 h after the first. The action of pertussis on a newly inflicted cryoinjury was protective. It is suggested that permeability changes in the cerebral vessels may be involved in the evolution of the encephalopathy attributed to the use of Bordetella pertussis vaccine in man.

Animals↗

PubMed1976

Histamine hypersensitivity in mice induced by Bordetella pertussis or pharmacologic beta adrenergic blockade. Effects of adrenergic, cholinergic, and other drugs.

The effects of prostaglandin E1, E2, F2alpha (PGE2 PGF2alpha), isoproterenol, epinephrine, norepinephrine, salbutamol, practolol, atropine, aminophylline, and corticosterone on the hypersensitivity to anaphylaxis, histamine, and serotonin in Bordetella pertussis-treated mice and propranolol-treated mice were investigated. Female HLA-SW (ICR) mice, 27-29 gm, were injected with pertussis vaccine intravenously 4 days before challenge with antigen, histamine, or serotonin. Alternatively, instead of pertussis vaccine, propranolol was injected intraperitoneally 45 min before histamine challenge. Test drugs were administered intraperitoneally 15 min before challenge. PGE1 and PGE2 at a narrow range of between 10 and 100 mug and epinephrine at 100 mug protected both pertussis- and propranolol-treated mice. Isoproterenol (25 mug) and aminophilline (800 mug) protected beta-blocked mice, but did not protect pertussis-treated mice even with very high doses (1,000 and 3,2000 mug, respectively), although salbutamol (500 mug) did. PGF2alpha, norepinephrine, and atropine were not protective at all. Practolol, a beta 1-blocker, given intraperitoneally 30 min before histamine neither sensitized normal mice nor changed the effect of isoproterenol or salbutamol in pertussis-treated mice. Corticosterone 10 mg/kg reduced the number of deaths from histamine in beta-blocked mice, but not in pertussis-treated mice. The protective effect is discussed in connection with probable effects of the drugs on intracellular cyclic adenosine monophosphate (cAMP) levels.

Adrenergic beta-Antagonists↗

PubMed1979

Pertussis vaccine--an analysis of benefits, risks and costs.

Using decision analysis, we estimated the benefits, risks and costs of routine childhood immunization against pertussis. Without an immunization program, we predict that there would be a 71-fold increase in cases and an almost fourfold increase in deaths (2.0 to 7.6) per cohort of one million children. With a vaccination program, we predict 0.1 case of encephalitis associated with pertussis and five cases of post-vaccination encephalitis; without a program, there would be only 2.3 cases of encephalitis associated with pertussis. Community vaccination would reduce by 61 per cent the costs related to pertussis. Our analysis supports continuation of vaccination in routine childhood immunization programs, but suggests the need for more reliable data on complications from the vaccine, further study of the epidemiology of pertussis and development of a less toxic vaccine.

Child↗

PubMed1978

Bordetella pertussis does not induce beta-adrenergic blockade.

Bordetella pertussis organisms induce histamine sensitivity and diminish the normal hyperglycemic response to epinephrine in experimental animals. These effects have been attributed to beta-adrenergic blockade. However, under conditions in which the decrease in epinephrine-induced hyperglycemia after B. pertussis administration was demonstrable, there was no change in rat reticulocyte beta-adrenergic receptor number or affinity measured by iodohydroxybenzylpindolol binding or in isoproterenol-stimulated adenylate cyclase activity. Therefore, there was no generalized beta-adrenergic blockade induced by B. pertussis. The observed effects can be explained by the hypersecretion of insulin resulting from B. pertussis administration.

Adenylyl Cyclases↗

PubMed2005

Bordetella pertussis risA, but not risS, is required for maximal expression of Bvg-repressed genes.

Expression of virulence determinants by Bordetella pertussis, the primary etiological agent of whooping cough, is regulated by the BvgAS two-component regulatory system. The role of a second two-component regulatory system, encoded by risAS, in this process is not defined. Here, we show that mutation of B. pertussis risA does not affect Bvg-activated genes or proteins. However, mutation of risA resulted in greatly diminished expression of Bvg-repressed antigens and decreased transcription of Bvg-repressed genes. In contrast, mutation of risS had no effect on the expression of Bvg-regulated molecules. Mutation of risA also resulted in decreased bacterial invasion in a HeLa cell model. However, decreased invasion could not be attributed to the decreased expression of Bvg-repressed products, suggesting that mutation of risA may affect the expression of a variety of genes. Unlike the risAS operons in B. parapertussis and B. bronchiseptica, B. pertussis risS is a pseudogene that encodes a truncated RisS sensor. Deletion of the intact part of the B. pertussis risS gene does not affect the expression of risA-dependent, Bvg-repressed genes. These observations suggest that RisA activation occurs through cross-regulation by a heterologous system.

Bacterial Adhesion↗

PubMed1975

Immunologic and biochemical properties of the histamine-sensitizing factor from Bordetella pertussis.

A highly potent extract of the histamine sensitizing factor (HSF) of Bordetella pertussis was isolated by extraction of bacterial cells with urea buffer and subsequent gel filtration. This preparation of HSF also contained leukocytosis-promoting activity and adjuvant activity for reaginic and hemagglutinating antibodiesl Digestion of this extract with pronase or trypsin partially destroyed histamine-sensitizing activity, leukocytosis-promoting activity, and adjuvant activity for reaginic antibody, but did not affect adjuvant activity for hemagglutinating antibody. Antisera to HSF was prepared by immunizing rabbits with either whole bacteria or partially purfied extract. These antisera contained several precipitating antibodies to Bordetella pertussis extract demonstrated by immunodiffusion and immunoelectrophoresis. Antisera added in vitro to Bordetella pertussis extracts or passively administered in vivo to mice, reduced or abolished all biologic activities except adjuvant activity for hemagglutinating antibody. These results suggest that HSF might be an antigenic component of Bordetella pertussis which also possesses leukocytosis-promoting activity and adjuvant activity for reaginic antibody.

Adjuvants, Immunologic↗

PubMed1976

The effect of Bordetella pertussis on the antibody response in mice to type III pneumococcal polysaccharide.

The effect of an i.p. injection of Bordetella pertussis on the primary humoral immune response in mice to the thymus-independent antigen SIII has been studied. Suppression of the antibody response occurred when pertussis cells were injected at the same time as an optimal immunizing dose of SIII. In contrast, the antibody response to high doses of SIII was enhanced by B. pertussis. When SIII alone was injected, only 19S antibody was detected. However, when B. pertussis was administered with either optimal or high doses of SIII, 7S as well as 19S antibody against SIII was produced.

Animals↗

PubMed1975

Taxonomic distribution of the antigen eliciting bactericidal antibody for Bordetella pertussis.

Strains of Bordetella pertussis varied in their ability to elicit (in mice) an antibody bactericidal for an antiserum-sensitive strain of B. pertussis, although antibody was usually detectable after only one injection. High titres were produced by a course of seven injections with all strains of B. pertussis tested (six of phase I and three of phase IV) but not with three strains of other Bordetella species nor with two unrelated organisms, a finding of possible taxonomic value. Preliminary investigations have not revealed whether strain vaiations are due to quantitative or qualitative differences in either the bacterial lipopolysaccharide or the carrier protein necessary for antibody production, or whether they may be due to differences in heat lability of 'bactericidal antigen'.

Adjuvants, Immunologic↗

PubMed1975

The antibody responses to myelin basic protein (BP) in Lewis rats: the effects of Bordetella pertussis.

A time-course study was made of the systemic humoral immune response of Lewis rats to myelin basic protein (BP) as influenced by the dosage of ancillary pertussis adjuvant. Peak activities were observed 5 to 7 weeks after injection. When injected proximal to BP and Mycobacterium butyricum in complete Freund's adjuvant (CFA), Bordetella pertussis at the level of 4 billion organisms doubled the antibody-binding activity of rat sera for 125I-labeled BP as compared to activities obtained with 0, 2, 6, or 8 billion. The severity of clinical symptoms of experimental allergic encephalomyelitis (EAE) at the end of the 2nd week was greatest in rats receiving 64 billion organisms, the very same rats that displayed a severely dampened humoral immune response to BP 5 weeks later. When pertussis was injected i.p. rather than proximal to the CFA mixture, the time-course of the humoral immune response displayed a different profile--unusually high binding activities at the time of onset of EAE that fluctuated back and forth from high to low and that eventually dampened to an intermediate level.

Animals↗

PubMed1976

The influence of growth medium on the interactions between Bordetella pertussis and Staphylococcus aureus.

Previous observers showed that many strains of Staphylococcus aureus stimulated the growth of Bordetella pertussis but we have found the reverse: the growth of all available strains of B. pertussis on charcoal-agar medium was inhibited by a standard strain of S. aureus; and 17 of 18 strains of S. aureus (as well as several other organisms) inhibited the growth of a standard strain of B. pertussis. All inhibiting colonies had an unusual brown colouration on the charcoal agar used in the investigation. Both the brown colouration and the inhibitory property were caused by acid production, probably from the starch in the medium. We therefore suggest that media containing starch and blood should not be used in studies of bacterial interference.

Agar↗

PubMed1977

[Complications of pertussis immunization (author transl)].

16 cases of neurological disease and/or death shortly after pertussis immunization are reported. Eight patients had convulsions, six with ensuing permanent defects. Severe polymyositis was observed in one case. Five infants died 12 h to 4 days after vaccination: two after acute encephalopathy and three in the form of a sudden unexpected death (SID). In two fatal cases the morphological changes in the brain corresponded to those of pertussis encephalopathy: neuronal degeneration in various parts of the cortex, especially in the region of the ammons horn, and in the cerebellum. There were no signs of inflammation. Three cases underwent forensic autopsy and death was attributed to bronchopulmonary infection. Complete neuropathological work-up was only done in one case, in which the brain was normal. The critique of episodical reports and the demand for prospective studies is appreciated. Knowledge of all possible forms of complications, however, is indispensable for future investigations. Polymyositis and SID have so far not been listed as abnormal reactions to immunization. The majority of our cases became known accidentally from hospital sheets or from discussions with collegues. For a detection of all possible cases a greater awareness of doctors for the problem of pertussis immunization appears necessary. Only another 23 cases have been reported to the health authorities of the state of Lower Saxony during the last 6 to 7 years. Of those, nine were either harmless reactions or diseases probably unrelated to vaccination. Two were cases of SID, 12 and 72 h after vaccination. It is concluded that only a minor proportion of possible complications is presently reported to the health authorities.

Brain↗

PubMed1977

Adenyl cyclase in Bordetella pertussis vaccines.

Brodetella pertussis organisms have a large amount of extracytoplasmic adenyl cyclase, part of which is found in the supernatant culture medium during exponential growth. The enzyme differs from previously studied bacterial adenyl cyclases in biochemical characteristics as well as in location. Several commercial pertussis vaccines were found to contain adenyl cyclase activity; this activity is probably due to the extracytoplasmic enzyme associated with and released from the whole cells in the vaccine.

Adenylyl Cyclases↗

PubMed1976

Isolation and properties of the leukocytosis- and lymphocytosis-promoting factor of Bordetella pertussis.

The leukocytosis- and lymphocytosis-promoting factor (LPF) of Bordetella pertussis has been isolated to near homogeneity by physical, chemical, and electron microscopical criteria. LPF contains 14.5% nitrogen and is lipid and carbohydrate free. It is apparently composed of four polypeptide subunits. LPF caused leukocytosis and lymphocytosis in "nude" as well as in normal mice. In addition, purified LPF also induced histamine sensitization and hypoglycemia and refractoriness to the hyperglycemic effect of epinephrine. A monospecific LPF antiserum blocked these reactions as well as leukocytosis and lymphocytosis. LPF is clearly distinct from the hemagglutinating pili of B. pertussis.

Amino Acids↗