TABLE 2.
Candidate colistin resistance genes identified as significant by Fisher’s exact test of daily populationsa
| Gene by functionb | No. of mutation events | Function | P value | Comments |
|---|---|---|---|---|
| LPS modification | ||||
| pmrB | 19 | Sensor kinase of two-component system, PmrAB | 4.41E−22 | Also identified in Fisher’s exact test of endpoint isolates |
| PA0011 | 9 | Probable 2-OH-lauroyltransferase | 3.19E−10 | Also identified in Fisher’s exact test of endpoint isolates |
| pmrA | 4 | Response regulator of two-component system, PmrAB | 2.15E−04 | Involved in polymyxin resistance (54) |
| Biofilm synthesis | ||||
| pelA | 13 | Modification and secretion system for Pel polysaccharide-dependent biofilm | 6.44E−10 | Mutations in Pel polysaccharide genes also identified previously (10, 12) |
| pslA | 8 | Psl polysaccharide synthesis and biofilm formation | 2.85E−07 | Also identified in Fisher’s exact test of endpoint isolates |
| pslN | 4 | Involved in Psl biosynthesis | 9.81E−04 | Part of operon containing pslA |
| Unknown role | ||||
| wspA | 9 | Probable chemotaxis transducer | 5.53E−08 | |
| PA1336 | 8 | Probable two-component sensor | 2.24E−06 | |
| PA3272 | 11 | Probable ATP-dependent DNA helicase | 4.02E−06 | Mutation in PA3272 also identified previously (12) |
| ostA | 9 | Organic solvent tolerance protein | 4.28E−06 | |
| vfr | 5 | Transcriptional regulator | 1.04E−05 | |
| PA4133 | 6 | Cytochrome c oxidase subunit (cbb3 type) | 4.17E−05 | |
| PA4021 | 6 | Probable transcriptional regulator | 2.13E−04 | |
| PA4873 | 5 | Probable heat shock protein | 2.42E−04 | |
| pqqD | 3 | Pyrroloquinoline quinone biosynthesis protein D | 2.58E−04 | |
| exbB1 | 4 | Transport protein ExbB | 2.89E−04 | |
| PA2802 | 4 | Probable transcriptional regulator | 2.89E−04 | |
| ureD | 4 | Urease accessory protein | 5.19E−04 | |
| pqqF | 6 | Pyrroloquinoline quinone biosynthesis protein F | 5.64E−04 | |
| hitB | 5 | Iron (III) transport system permease | 5.83E−04 | |
| PA0181 | 4 | Probable transcriptional regulator | 7.55E−04 | |
| PA4180 | 5 | Probable acetolactate synthase large subunit | 7.82E−04 | |
| PA3900 | 4 | Probable transmembrane sensor | 8.20E−04 | |
| PA0041 | 13 | Probable hemagglutinin | 8.20E−04 | |
| PA2511 | 4 | Probable transcriptional regulator | 9.81E−04 | |
a
Genes within the Pf4 phage encoded region identified by this test were excluded from this table. Genes encoding hypothetical proteins identified by this test are listed in Table S2. Genes migA and algP were identified as significant but were also identified in the control population evolved in the absence of colistin. Hence, those genes are considered to be involved in adaptation to the bioreactor rather than the drug.
b
LPS, lipopolysaccharide.