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PreprintCC BY-NCbioRxiv

Cryptic Genes as Building Blocks of Antimicrobial Resistance: Evidence from a Novel Marine Imipenem-Hydrolyzing Metallo-β-Lactamase

  1. 1CSIR-Central Drug Research Institute

Abstract

The emergence of antimicrobial resistant pathogens has led to increase in mortality rate, longer hospital stays, and need for complex and expensive treatment regimens. However, it is not very clear from where does the bacteria get the building blocks to 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 putative 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 putative cryptic metallo beta lactamase 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 putative cryptic antimicrobial resistance genes to fully address and mitigate the challenges posed by antimicrobial resistance.

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BibTeX
@misc{gupta2026cryptic,
  title = {{Cryptic Genes as Building Blocks of Antimicrobial Resistance: Evidence from a Novel Marine Imipenem-Hydrolyzing Metallo-β-Lactamase}},
  author = {P. Gupta and P. Yadav and J. Kishan and S. Gupta and S. Shaw and K. Goswami and V. C. Tripathi and K. Mitra and J. V. Pratap and J. Arockiaraj and M. Pasupuleti},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.09.750327},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750327v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - Cryptic Genes as Building Blocks of Antimicrobial Resistance: Evidence from a Novel Marine Imipenem-Hydrolyzing Metallo-β-Lactamase
AU  - P. Gupta
AU  - P. Yadav
AU  - J. Kishan
AU  - S. Gupta
AU  - S. Shaw
AU  - K. Goswami
AU  - V. C. Tripathi
AU  - K. Mitra
AU  - J. V. Pratap
AU  - J. Arockiaraj
AU  - M. Pasupuleti
PY  - 2026
DA  - 2026/09/09
PB  - bioRxiv
DO  - 10.64898/2026.09.09.750327
UR  - https://www.biorxiv.org/content/10.64898/2026.09.09.750327v1
AB  - The emergence of antimicrobial resistant pathogens has led to increase in mortality rate, longer hospital stays, and need for complex and expensive treatment regimens. However, it is not very clear from where does the bacteria get the building blocks to 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 putative 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 putative cryptic metallo beta lactamase 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 putative cryptic antimicrobial resistance genes to fully address and mitigate the challenges posed by antimicrobial resistance.
ER  -