TABLE 5.
Summary of hypothesized chemical triggers and of transcriptomic, metabolomic, and mutant susceptibility evidence for stress response or metabolic activities influencing ciprofloxacin tolerance in P. aeruginosa biofilmsa
| Chemical triggerb | Activityc | Gene overexpressiond | Mutant evidence |
|---|---|---|---|
| O2 depletion | O2 downshift | 38/117 (32) | Not tested |
| Hypoxic growth | 43/159 (27) | Not tested | |
| Anr+ regulon | Not significant | Not tested | |
| Denitrification | 7/9 (78) | nirS, norB | |
| Stationary phase | 148/250 (59) | Not tested | |
| Stringent response | Not mapped | ΔrelA ΔspoT | |
| RpoS+ regulon | 108/423 (26) | ΔrpoS | |
| Unknown | PSL biosynthesis | 0/12 (0) | ΔpslA |
| PEL biosynthesis | 0/7 (0) | pelA | |
| Alginate biosynthesis | 0/12 (0) | algD | |
| AHL accumulation | AHL quorum sensing | 25/72 (35) | Not tested |
| Rhamnolipid production | 6.7 FC | rhlB | |
| Lectin production | 29.7, 60.4 FC | lecA, lecB | |
| PQS accumulation | Pyocyanin biosynthesis | 7/17 (41) | phzS |
| MvfR+ regulon | 50/115 (43) | Not tested | |
| Zn depletion | Zn limitation | 26/44 (59) | Not tested |
| Osmotic stress | Osmotic stress response | 12/56 (21) | osmE |
| Unknown | Glyoxylate shunt | 1/2 (50) | aceA |
| Isocitrate lyase | 3.4 FC | aceA | |
| Malate synthase | 1.06 FC | Not tested | |
| Mistranslated proteins? | Membrane stress | 1/14 (7) | amgR |
Light shading indicates logical concordance with the identified chemical trigger, annotated activity, or effect on biofilm antimicrobial susceptibility, whereas dark shading indicates a contradiction of the hypothesis that the upregulated gene affords protection from killing by ciprofloxacin.
AHL, acyl-homoserine lactone; PQS, Pseudomonas quinolone signal.
PSL and PEL, polysaccharide synthesis locus and pellicle polysaccharides, respectively. Plus signs with regulons indicate positive regulation.
Given as the number of overexpressed genes on the current study list/number of genes on the target activity list (percentage of target list genes that are overexpressed in the current study) or as the fold change (FC) in expression. The current study list has a total of 449 genes.