Systems-level analysis of NalD mutation, a recurrent driver of rapid drug resistance in acute Pseudomonas aeruginosa infection
Fig 4
NalD mutation contributes to a general signature of antibiotic resistance.
(A) A signature of aztreonam resistance obtained with LASSO regression shows only two transcriptional regulators, including NalD, and explains >60% of the variation in aztreonam MIC. The coefficients have units of fold-change. (B) Antibiotic inhibitions zones were measured using the disk assay for 8 antibiotics from several classes. The inhibition zone indices (shows as normalized areas of inhibition disk) show that the 8 sepsis isolates are resistant to multiple antibiotics. A resistance index computed from combining the negative values of the inhibition zone indices shows that the 8 sepsis isolates rank higher in multi-drug resistant than any other isolate tested. (C) The signature of multi-antibiotic resistance has six transcriptional regulators, including NalD, and explains >80% of the variation in the multi-drug resistance index. The coefficients have units of integrated fold-change across all the 8 antibiotics.