For more information check out the paper.

This was a great team effort led by Fabrice Graf from LSTM and it's great to see it finally published!

Together this shows:

(i) that antibiotic susceptibility can re-emerge after an antibiotic stops being used

(ii) that genetic context should be included in AMR databases

(iii) that chloramphenicol could be reintroduced in certain contexts (e.g critically ill with ESBL-E)

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We then used co-occurrence analysis on a larger dataset of short-read E. coli and K. pneumoniae genomes (n=772) which showed that the catB3∆443–633 (i.e. catB4 in figure) and catB3 genes nearly always co-occurred with aac(6')-Ib-cr, blaOXA-1 and the ESBL gene blaCTX-M-15.

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Another IS element, IS5, was found to insert into the promoter region of catA1, again knocking out its function. This shows how it is important to consider the gene environment along with the gene presence or absence in AMR gene detection and surveillance.

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This truncated catB3 gene (catB3∆443–633) appears as catB4 in some AMR gene databases, even though it doesn't confer phenotypic resistance this results in false positives and genotype-phenotype mismatches.

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Using functional studies and genomics, we found that IS elements were part of the molecular mechanisms driving the rise in chloramphenicol susceptibility. IS26 was found to truncate the chloramphenicol resistance gene catB3, knocking out its function.

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