Systems-level analysis of NalD mutation, a recurrent driver of rapid drug resistance in acute Pseudomonas aeruginosa infection
Fig 3
Whole-genome sequencing of eight P. aeruginosa isolates pinpointed the mutation NalDF198L responsible for aztreonam resistance detected one day before the patient died.
(A) A genome-based phylogenetic tree shows that the eight sepsis isolates are highly related to each other compared to other clinical isolates and type strains. (B) Genomic analysis revealed that the aztreonam-resistant isolate (D+7bld) had only two unique variations compared to aztreonam-sensitive isolates. Vertical dashed lines highlight the common presence of a given variation across multiple isolates. (C) Aztreonam MIC confirmed the clinical laboratory results for the eight sepsis isolates. (D) Experimental validation in PA14 showed that mutation in NalD but not in peg.4653 (PA14_50010) confers aztreonam resistance. “-”and “+” denote absence or presence of mutation found in D+7bld; “Δ” denotes deletion of the 10th alpha helix in NalD protein. (**, p-value<0.01).