Mycoplasma hyorhinis‐encoded cytidine deaminase efficiently inactivates cytosine‐based anticancer drugs

Mycoplasmas may colonize tumor tissue in patients. The cytostatic activity of gemcitabine was dramatically decreased inMycoplasma hyorhinis‐infected tumor cell cultures compared with non‐infected tumor cell cultures. This mycoplasma‐driven drug deamination could be prevented by exogenous administration of the cytidine deaminase (CDA) inhibitor tetrahydrouridine, but also by the natural nucleosides or by a purine nucleoside phosphorylase inhibitor. TheM. hyorhinis‐encoded CDAHyor gene was cloned, expressed as a recombinant protein and purified. CDAHyor was found to be more catalytically active than its human equivalent and efficiently deaminates (inactivates) cytosine‐based anticancer drugs. CDAHyor expression at the tumor site may result in selective drug inactivation and suboptimal therapeutic efficiency