Cryptic genes as evolutionary precursors of antimicrobial resistance: Marine bacterium Cytobacillus oceanisediminis encodes a sequence-divergent highly selective imipenem-degrading enzyme
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The emergence of antimicrobial resistant pathogen has led to increase in mortality rate, longer hospital stays, and need for complex and expensive treatment regimens. However, it is not clear how does the bacteria develop resistance to these synthetic antimicrobial agents which have been integral part of modern medicine. One hypothesis is that non-coding cryptic genes without any vital function or positive contribution to fitness act as versatile endogenous genetic repertoires that help in bacterial adaptation and evolution of new phenotypes when conditions change. This study reports the presence of cryptic metallo beta lactamase gene in the marine bacterium Cytobacillus oceanisediminis isolated from the Gulf of Mannar, India. Using in silico , in vitro and in vivo assay, we demonstrate that the BMBL282 in C. oceanisediminis encodes an enzyme that can cleave only imipenem, has two characteristic domains: HXHXDH and TPGH, but does not share homology with the other reported Metallo-beta-Lactamase genes. The findings underscore the importance for comprehensive screening of cryptic antimicrobial resistance genes to fully address and mitigate the challenges posed by antimicrobial resistance. To the best of our knowledge, this is the first report of presence of cryptic gene in the Marine bacterium C. oceanisediminis that can degrade imipenem but not the other antibiotics of the carbapenem family.
Importance
One fundamental question that needs to be addressed in antimicrobial resistance evolution is, “how does bacteria get the building blocks for the genesis of antimicrobial resistant genes”?. Based on the in silico, in vitro and in vivo assay data, we propose that BMBL282 is a novel antimicrobial resistant cryptic gene with imipenem-degrading ability without any sequence or structure homology to reported ones and might belong to the newly proposed B3b subgroup of Metallo beta lactamase. This work clearly demonstrate that cryptic genes act as versatile endogenous genetic repertoires that help the bacterial in adaptation and evolution when required.
