The impacts of L1 promoter variation and L2 clavulanate susceptibility on ticarcillin-clavulanate susceptibility of Stenotrophomonas maltophilia [Mechanisms of Resistance]

Inducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactam for S. maltophilia treatment. Clavulanate (CA) is a β-lactamase inhibitor which specifically targets to Class A, C, and D β-lactamases. In view of the presence of class B L1 β-lactamase, it is of interest to elucidate why TIM is valid for S. maltophilia treatment. The L1, L2 allelic variation and TIM susceptibility from 22 clinical isolates were established. According to L1 and L2 protein sequences and TIM susceptibility, three L1-based phylogenetic clusters (L1-A, L1-B, and L1-C) and three L2-based phylogenetic clusters (L2-A, L2-B1, and L2-B2) were classified. The contribution of each L1- and L2-based phylogenetic cluster to ticarcillin (TIC) and TIM susceptibility was investigated. All L1s and L2s tested contributed to TIC resistance. L1s tested were inert to CA; nevertheless, the sensitivities of L2s toward CA were greatly different. In addition, the genetic organizations upstream of the L1 gene much varied in these isolates. At least three different L1 promoter structure (K279a-type, D457-type, and none) were found from the 22 isolates assayed. The difference in the L1 promoter structure made a great impact on the TIC-induced L1 β-lactamase activities. Collectively, the L1 promoter activity responding to TIC challenge and L2 susceptibility toward CA are critical factors determining TIM susceptibility in S. maltophilia.

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