Table 3.
Mutations that occurred in 34 genes during airway infections in 29 CF patients
| Gene name† | Gene annotation no. | Gene function | No. of nonsynonymous mutations (nonsense) | No. of synonymous mutations | No. of insertions/deletions (frameshifts and transposon insertions) | No. of intergenic mutations | Total no. of independent mutations‡ | No. of patients with at least one mutated isolate |
|---|---|---|---|---|---|---|---|---|
| mexZ | PA2020 | Transcriptional regulator of multidrug efflux | 13 (5) | 0 | 11 (9) | 0 | 24 | 18 |
| lasR | PA1430 | Transcriptional regulator of quorum sensing | 18 (3) | 0 | 4 (4) | 0 | 22 | 18 |
| PA0313 | Probable permease of ABC transporter | 4 (1) | 0 | 10 (2) | 1 | 15 | 13 | |
| mexA | PA0425 | RND multidrug efflux membrane fusion protein MexA precursor | 13 (4) | 0 | 1 (1) | 0 | 14 | 11 |
| accC | PA4848 | Biotin carboxylase | 6 | 0 | 3 (2) | 0 | 9 | 9 |
| *vfr | PA0652 | Transcriptional regulator | 4 | 0 | 3 (2) | 1 | 8 | 7 |
| mexS | PA2491 | Probable oxidoreductase | 7 | 0 | 1 | 0 | 8 | 6 |
| exsA | PA1713 | Transcriptional regulator of type III secretion | 6 | 0 | 2 (1) | 0 | 8 | 6 |
| PA0506 | Probable acyl-CoA dehydrogenase | 5 | 0 | 1 (1) | 1 | 7 | 7 | |
| *wspF | PA3703 | Probable methylesterase involved in chemosensory signal transduction | 4 (2) | 0 | 2 (1) | 0 | 6 | 6 |
| *rpoN | PA4462 | RNA polymerase σ-54 factor | 2 (1) | 0 | 3 (2) | 0 | 5 | 5 |
| *fleQ | PA1097 | Transcriptional regulator of flagella synthesis | 5 (1) | 0 | 0 | 0 | 5 | 5 |
| mexT | PA2492 | Transcriptional regulator of multidrug efflux | 4 | 0 | 0 | 1 | 5 | 5 |
| *nalD | PA3574 | Probable transcriptional regulator | 1 | 1 | 1 (1) | 1 | 4 | 4 |
| *ampD | PA4522 | β-Lactamase expression regulator | 3 | 0 | 1 | 0 | 4 | 4 |
| PA0366 | Probable aldehyde dehydrogenase | 1 | 0 | 2 (2) | 1 | 4 | 4 | |
| *cyaB | PA3217 | Adenylate cyclase | 2 | 1 | 0 | 0 | 3 | 3 |
| P1-001 | In 45-kb genomic island§ | Hypothetical protein | 1 | 0 | 2 (2) | 0 | 3 | 2 |
| PA3817 | Probable methyltransferase | 2 | 1 | 0 | 0 | 3 | 3 | |
| pilB | PA4526‡ | Type 4 fimbrial biogenesis protein | 1 | 1 | 0 | 0 | 2 | 2 |
| PA1333 | Hypothetical protein | 0 | 0 | 0 | 1 | 1 | 1 | |
| PA3565 | Probable transcriptional regulator | 1 | 0 | 0 | 0 | 1 | 1 | |
| PA2312 | Probable transcriptional regulator | 0 | 1 | 0 | 0 | 1 | 1 | |
| *anr | PA1544 | Transcriptional regulator of anaerobic metabolism | 0 | 0 | 0 | 1 | 1 | 1 |
| *rhlR | PA3477 | Transcriptional regulator of quorum sensing | 0 | 0 | 0 | 1 | 1 | 1 |
| *phoP | PA1179 | Two-component response regulator | 0 | 0 | 0 | 0 | 0 | 0 |
| rhlI | PA3476 | Autoinducer synthesis protein | 0 | 0 | 0 | 0 | 0 | 0 |
| PA4796 | Hypothetical protein | 0 | 0 | 0 | 0 | 0 | 0 | |
| pqsB | PA0997 | Homologous to β-keto-acyl-acyl-carrier protein synthase | 0 | 0 | 0 | 0 | 0 | 0 |
| toxR | PA0707 | Transcriptional regulator | 0 | 0 | 0 | 0 | 0 | 0 |
| PA2435 | Probable cation-transporting P-type ATPase | 0 | 0 | 0 | 0 | 0 | 0 | |
| PA4420 | Hypothetical protein | 0 | 0 | 0 | 0 | 0 | 0 | |
| None§ | Hypothetical protein ORF C/SG114 | 0 | 0 | 0 | 0 | 0 | 0 | |
| PA2121 | Hypothetical protein | 0 | 0 | 0 | 0 | 0 | 0 | |
| Total | 103 (17) | 5 | 47 (30) | 9 | 164 | 143 |
†The 10 gene names that are preceded by an asterisk were candidate genes based on other studies. The remaining 24 genes were mutated in the 96-month isolate of patient 1.
‡Each gene was amplified with PCR and completely sequenced in 91 isolates. Most patients had three representative isolates that had been collected longitudinally. A mutation was defined as any difference in sequence between clonally related isolates from the same patient. When the same mutation was present in multiple isolates from the same patient, we assumed that the mutation occurred once during the infection and was then propagated clonally. Some patients had two isolates with different mutations in the same gene; we considered these as two independent mutations.
§Two genes are not present in all strains: the gene P1-001 is present in isolates from five patients, and gene C/SG114 is present in isolates from 21 patients. pilA and pilB were only partially sequenced because the locus exhibits high strain-to-strain divergence.