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

antimicrobial agents and chemotherapy

ClpA and HtpX Proteases Are Involved in Intrinsic Aminoglycoside Resistance of Stenotrophomonas maltophilia and Are Potential Aminoglycoside Adjuvant Targets