ClpA and HtpX proteases are involved in intrinsic aminoglycoside resistance of stenotrophomonas maltophilia and are potential aminoglycoside adjuvant targets

The linkage of the protease-chaperon system, SmeYZ pump, and aminoglycoside resistance was assessed in Stenotrophomonas maltophilia. The clpA, clpS, clpP, and htpX genes were upregulated in response to kanamycin exposure. Of these, clpA and htpX were the primary determinants responsible for intrinsic aminoglycoside (AG) resistance. Inactivation of clpA and htpX compromised protease-mediated intrinsic aminoglycoside resistance and weakened SmeYZ pump-mediated aminoglycoside resistance, signifying HtpX and ClpA as potential AG adjuvant targets for treatment of S. maltophilia infections.