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

FEBS Open Bio. 2015 Aug 3;5:634-9. doi: 10.1016/j.fob.2015.07.007. eCollection 2015.

Abstract

Mycoplasmas may colonize tumor tissue in patients. The cytostatic activity of gemcitabine was dramatically decreased in Mycoplasma 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. The M. 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.

Keywords: (d)Ado, (2′-deoxy)adenosine; (d)Guo, (2′-deoxy)guanosine; (d)Ino, (2′-deoxy)inosine; (d)Urd, (2′-deoxy)uridine; 3TC, 2′,3′-dideoxy-3′-thiacytidine; CDA, cytidine deaminase; Cancer; Cytidine deaminase; Gemcitabine; Imm-H, Immucillin-H; Mycoplasma; NA, nucleoside analogue; Nucleoside analogue; PNP, purine nucleoside phosphorylase; Purine nucleoside phosphorylase; ara-Cyd, cytosine arabinoside; dFdC, gemcitabine; dFdU, 2′,2′-difluoro-2′-deoxyuridine; dThd, thymidine; ddC, 2′,3′-dideoxycytidine.