Capsules, Toxins and AtxA as Virulence Factors of Emerging Bacillus cereus Biovar anthracis

Abstract

Emerging B. cereus strains that cause anthrax-like disease have been isolated in Cameroon (CA strain) and Côte d’Ivoire (CI strain). These strains are unusual, because their genomic characterisation shows that they belong to the B. cereus species, although they harbour two plasmids, pBCXO1 and pBCXO2, that are highly similar to the pXO1 and pXO2 plasmids of B. anthracis that encode the toxins and the polyglutamate capsule respectively. The virulence factors implicated in the pathogenicity of these B. cereus bv anthracis strains remain to be characterised. We tested their virulence by cutaneous and intranasal delivery in mice and guinea pigs; they were as virulent as wild-type B. anthracis. Unlike as described for pXO2-cured B. anthracis, the CA strain cured of the pBCXO2 plasmid was still highly virulent, showing the existence of other virulence factors. Indeed, these strains concomitantly expressed a hyaluronic acid (HA) capsule and the B. anthracis polyglutamate (PDGA) capsule. The HA capsule was encoded by the hasACB operon on pBCXO1, and its expression was regulated by the global transcription regulator AtxA, which controls anthrax toxins and PDGA capsule in B. anthracis. Thus, the HA and PDGA capsules and toxins were co-regulated by AtxA. We explored the respective effect of the virulence factors on colonisation and dissemination of CA within its host by constructing bioluminescent mutants. Expression of the HA capsule by itself led to local multiplication and, during intranasal infection, to local dissemination to the adjacent brain tissue. Co-expression of either toxins or PDGA capsule with HA capsule enabled systemic dissemination, thus providing a clear evolutionary advantage. Protection against infection by B. cereus bv anthracis required the same vaccination formulation as that used against B. anthracis. Thus, these strains, at the frontier between B. anthracis and B. cereus, provide insight into how the monomorphic B. anthracis may have emerged.

The roles of AtxA orthologs in virulence of anthrax‐like Bacillus cereus G9241

“…However, when the hasACB locus was deleted and pBCXO2 was cured, the toxigenic, but nonencapsulated, mutant was severely attenuated in mice after s.c. challenge with an LD 50 similar to that of Sterne strain 7702. Further, a spontaneous atxA mutant in the pBCXO1+/pBCXO2‐strain produced neither the HA capsule nor the toxin components and was avirulent (Brezillon et al ., ). Oh et al .…”

Assembly and Function of the Bacillus anthracis S-Layer

“…B. cereus G9241 and its close relatives were isolated in North America from humans with severe pneumonia or cutaneous anthrax-like disease (55, 86). pXO1-like plasmids of B. cereus isolates provide for the expression of hyaluronic acid (HA) capsule via the hasACB operon, which is mutated and nonfunctional in B. anthracis (16, 104) (Figure 1). B. cereus biovar anthracis CI produces both HA and PDGA capsular material, as these strains acquired a pXO2-like plasmid (6, 16, 66).…”

“…pXO1-like plasmids of B. cereus isolates provide for the expression of hyaluronic acid (HA) capsule via the hasACB operon, which is mutated and nonfunctional in B. anthracis (16, 104) (Figure 1). B. cereus biovar anthracis CI produces both HA and PDGA capsular material, as these strains acquired a pXO2-like plasmid (6, 16, 66). In contrast, B. cereus G9241 synthesizes HA in addition to another capsular polysaccharide designated BPS ( B .…”

“…cereus exo- p oly s accharide), which requires the expression of the bpsXABCDEFGH genes located on the pBC210 virulence plasmid (104) (Figure 1). B. cereus G9241 and B. cereus biovar anthracis CI express atxA and carry an inactivating mutation in their chromosomal plcR gene that is distinct from that of B. anthracis (6, 16, 125). pBC210 carries an atxA -like gene ( atxA2 ) that contributes to the pathogenesis of anthrax-like disease in B. cereus G9241 (125).…”

The Current Situation on Anthrax in Russia and in the World. Main Trends and Features

“…коэкспрессия гиалуро-новой капсулы как с токсинами, так и полиглутамат-ной капсулой, приводила к системной диссеминации возбудителя и придавала очевидное эволюционное преимущество таким вариантам. исследование этих штаммов, занимающих пограничное положение между B. anthracis и B. cereus, поможет получить новые представления о возникновении и эволюции вида B. anthracis [12]. этому в большой степени спо-собствуют претерпевшие бурное развитие методы молекулярного типирования штаммов возбудителя сибирской язвы и полногеномного секвенирования, что позволяет также сделать более объективной эпидемиологическую интерпретацию молекулярно-генетических данных эпидемиологического рассле-дования [23,24,42].…”