Characterization of a Unique Bordetella bronchiseptica vB_BbrP_BB8 Bacteriophage and Its Application as an Antibacterial Agent.

Bordetella bronchiseptica, an emerging zoonotic pathogen, infects a broad range of mammalian hosts. B. bronchiseptica-associated atrophic rhinitis incurs substantial losses to the pig breeding industry. The true burden of human disease caused by B. bronchiseptica is unknown, but it has been postulated that some hypervirulent B. bronchiseptica isolates may be responsible for undiagnosed respiratory infections in humans. B. bronchiseptica was shown to acquire antibiotic resistance genes from other bacterial genera, especially Escherichia coli. Here, we present a new B. bronchiseptica lytic bacteriophage-vB_BbrP_BB8-of the Podoviridae family, which offers a safe alternative to antibiotic treatment of B. bronchiseptica infections. We explored the phage at the level of genome, physiology, morphology, and infection kinetics. Its therapeutic potential was investigated in biofilms and in an in vivo Galleria mellonella model, both of which mimic the natural environment of infection. The BB8 is a unique phage with a genome structure resembling that of T7-like phages. Its latent period is 75 ± 5 min and its burst size is 88 ± 10 phages. The BB8 infection causes complete lysis of B. bronchiseptica cultures irrespective of the MOI used. The phage efficiently removes bacterial biofilm and prevents the lethality induced by B. bronchiseptica in G. mellonella honeycomb moth larvae.

Bordetella holmesii: Still Emerging and Elusive 20 Years On.

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.

Dysregulated macrophage-inflammatory protein-2 expression drives illness in bacterial superinfection of influenza.

Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR(+) inflammatory chemokine MIP-2 (CXCL2/GRO-beta) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza.

Treatment of mice with IL-12 DNA constructs leads to augmented NK activity in lungs but low IFN-gamma release -- implications for Bordetella pertussis infections following aerosol challenge.

Interleukin-12 protein has been widely used experimentally in therapeutic and adjuvant settings in the treatment of different diseases including intra-cellular bacterial infections. The in vivo clearance of Bordetella pertussis infections in naive mice and in animals vaccinated with whole cell vaccine is considered to be a Th-1 dependent mechanism. Furthermore, the addition of IL-12 protein to an acellular pertussis vaccine increases the efficacy of this vaccine. Whilst the use of IL-12 protein is often beneficial, a number of problems there are associated with this cytokine including toxicities and down regulation of normal immune functions. The use of DNA constructs encoding this cytokine may be a way of achieving maximum therapeutic benefit with minimum toxicity. The aims of this study were to optimise the effects of two IL-12 DNA constructs, especially with respect to augmenting pulmonary immune responsiveness and to compare the effect of IL-12 DNA and IL-12 protein on bacterial colonisation of lungs following aerosol challenge with B. pertussis. We found that IL-12 DNA constructs augmented the activity of pulmonary NK cells but had little effect on the course of B. pertussis infections in mice. In contrast to IL-12 protein, the DNA constructs had no immunosuppressive effects on splenic lymphocyte mitogen responses.

Bordetella bronchiseptica infection in the cat.

Feline Bordetella bronchiseptica infection had received little consideration until recent years when it has been increasingly documented in association with respiratory disease. This article reviews current knowledge on the organism; its epidemiology, pathogenesis, and clinical, diagnostic and therapeutic features.

Isolation of a Bordetella avium-like organism from a human specimen.

The isolation of a strain of Bordetella for which the species could not be determined but which most closely resembled Bordetella avium is reported. The strain was isolated in mixed culture from an ear swab of a patient suffering from chronic otitis media. The bacterium showed the typical biochemical reactions of Bordetella avium but differed in antimicrobial resistance pattern, protein and fatty acid composition, and DNA-DNA and DNA-rRNA hybridization. Further studies will clarify the taxonomic status of this strain within the Bordetella-Alcaligenes ribosomal RNA cluster.

Effect of human immunoglobulin preparations on experimental Bordetella pertussis infection in mice.

The effects of four kinds of human immunoglobulin preparations for intravenous use [pH-4-treated (IG-100), polyethyleneglycol-treated (PEG-G), sulfonated (S-G) and pepsin-treated (Pep-G)] on intracerebral (i.c.) Bordetella pertussis infection in mice, and on B. pertussis vaccine-induced leukocytosis-promoting factor (LPF) and histamine-sensitizing factor (HSF) were compared with those of human immunoglobulin preparation for intramuscular use (GGN). A prophylactic potential against i.c. B. pertussis challenge was demonstrated in IG-100, PEG-G and GGN. A prophylactic potential was also demonstrated in S-G and Pep-G, although to a lesser extent. Neutralizing activity for LPF was in the following order: GGN = IG-100 = PEG-G greater than S-G = Pep-G; for HSF it was as follows: IG-100 greater than PEG-G greater than GGN = S-G greater than Pep-G. There were no significant differences in antibody titers of the various preparations against B. pertussis antigens. These results suggest that the Fc part of the immunoglobulin molecule is important for protecting against i.c. B. pertussis infection and for neutralizing B. pertussis toxins.