Super-infection by Bacillus thuringiensis H34 or 3a3b can lead to death in mice infected with the influenza A virus

Abstract

Bacterial super-infections are the main cause of complication and mortality after influenza virus (IAV) infection. Since Bacillus thuringiensis (Bt) is considered non-pathogenic for humans and is widely sprayed in urban areas, the aim of this work was to evaluate the potential pathogenicity of a combined infection Bt-IAV in a mouse model of pneumonia. Bacteria used for super-infections were Bt serotype H34 isolated from human infection and the insecticidal strain 3a3b obtained from a commercial source. Virus strain was A/Scotland/20/74 (H3N2) adapted to BALB/c mice by serial lung passage. Combined infection with 4% of the viral lethal dose 50% (LD(50)) and 10(2) spores of Bt H34 killed 40% of the mice. Mortality rates increased up to 55% and 100% when combined infections were done with respectively 10(4) and 10(7) spores. The insecticidal strain Bt 3a3b was less pathogenic than Bt H34. A dose of 10(4) spores associated with 4% of IAV LD(50) killed 50% of the mice. This inoculum must be compared with the doses usually sprayed in agriculture: 10(11) spores m(-2). Total protection against super-infection was obtained when mice were treated with amantadine. Even if only a few cases of Bt human infection have been reported, these results suggest a possible risk for workers spraying Bt-based biopesticides during flu outbreaks.

Influenza A Virus-Infected Hosts Boost an Invasive Type ofStreptococcus pyogenesInfection in Mice

“…In addition, Locci (23) suggested that secondary bacterial infections, e.g., Staphylococcus aureus, GAS, group B streptococcus, Streptococcus pneumoniae, and Haemophilus influenzae, are closely associated with complications in influenza. Some groups of researchers have also found that infection with bacteria after IAV infection leads to the death of mice (11,14,17,22,24). In the present study, all mice infected with both IAV and GAS developed severe pneumonia (Fig.…”

Early murine immune responses from endotracheal exposures to biotechnology-relatedBacillusstrains

“…In contrast, many strains of the Bc group member Bacillus thuringiensis (Bt) are known to be entomopathic, and some of them have been developed for large-scale commercial use in forestry (e.g., against spruce budworm, gypsy moth), agriculture (e.g., against corn borer, tobacco budworm) and prevention of disease dissemination (e.g., against mosquitos, blackflies). However, there are reports that some Bt strains are infectious to humans, and similar in properties to Bc strains examined (Damgaard et al 1997; Hernandez et al 1998, 1999, 2000; Jackson et al 1995; McIntyre et al 2008; Samples and Buettner 1983). …”

Genomics of the group of organisms

“…The spores are associated with large crystal protein inclusions, which can make up to 25% of the dry weight of the spore preparations. In addition, like B. cereus, B. thuringiensis could be considered an opportunistic pathogen in animals and human [9][10][11]. Upon ingestion by insect larvae, the protoxin crystals solubilize in the mid-gut, where it is cleaved by a gut protease to produce an active toxin (d-endotoxins) of about 60 kDa.…”

“…A few genes encoding cytotoxin K and non-hemolytic enterotoxin C subunit, amongst others, have only been found in B. cereus [47]. While one can only infer the pathogenicity of B. cereus ZK based on its isolation from a dead zebra, the opportunistic pathogenicity of B. thuringiensis 97-27 has been confirmed by infection of both immunosuppressed and immunocompetent mice [9][10][11]. Interestingly, a recent study showed that a fused PlcR-PapR construct was able to restore strong hemolytic activities when introduced in B. anthracis [59], indicating that these genes, while not upregulated, are still fully functional and have not undergone evolutionary decay.…”