Cytotoxic Bacillus anthracis, Bacillus pacificus and Scardovia wiggsiae strains associated with Noma in Senegal
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Background
Noma is a deadly gangrenous disease that affects the mouth and face, mainly in children from tropical and subtropical regions living in extreme poverty. An infectious etiology is strongly suspected, but no causative microorganism has yet been identified. We therefore conducted an age- and sex-matched case-control culturomics study to isolate bacterial species associated with noma and assess their cytotoxicity, their genomic toxin content, and their antibiotic susceptibility.
Methods
A case-control study was conducted in 2023 in the Diourbel region (Senegal) among children aged 5 to 9 years. Gingival plaque samples were analyzed by microbial culturomics. In addition, cytotoxic tests were performed on MRC5 cells, followed by analysis of the toxin and antimicrobial resistance genomic content.
Results
A total of five cases of noma and five age- and sex-matched controls were included. 102 species were isolated, including five previously unknown species. The cariogenic species Streptococcus mutans and Scardovia wiggsiae were only detected in cases. Interestingly, all seven strains of S. wiggsiae were cytotoxic. Similarly, eight strains of the Bacillus cereus group were only identified in cases, including six cytotoxic strains. After genomic sequencing, six strains of Bacillus pacificus and two strains of Bacillus anthracis ( pXO1 and pXO2 negative) were identified. Genes encoding typical toxins ( hbl , nhe , ces , entFM , bceT , hlyIII ) and penicillin-specific β-Lactamase ( bla2 ) were found in all eight strains of the B. cereus group, but the bla gene and the necrotizing cytotoxins K1 ( cytK-1 ) and K2 ( cytK-2 ) were only identified in the two B. anthracis strains. Among the five new species, Ferdinandcohnia sokhnae sp. nov. was isolated from a child with noma and was cytotoxic. Overall, at least one cytotoxic strain was isolated from each case, but none were found in the controls. B. anthracis, B. pacificus and F. sokhnae strains were all susceptible to clindamycin and vancomycin but resistant to amoxicillin, amoxicillin/ clavulanic acid and metronidazole. In contrast, all S. wiggsiae strains were susceptible to amoxicillin and amoxicillin-clavulanic acid, but resistant to metronidazole.
Conclusion
A microbial specificity was observed in noma characterized by cytotoxic strains with the unexpected isolation of B. anthracis whose genome encoded a previously described necrotizing toxin gene ( CytK1 ). Antimicrobial resistance results did not support the use of amoxicillin nor metronidazole. Microbiota analysis using microbial culturomics was instrumental in these findings, which opens new avenues for understanding the mechanisms of the disease, and for improving WHO and UNICEF guidelines. Future precision medicine based on microbiological knowledge and diagnosis may improve its future clinical management.
