Table 2.
Virulence of Y. pestis with Fe, Mn, or Zn mutations in mouse models of bubonic, septicemic, and pneumonic plague.
| Strain or mutation (Function) | Bubonic plague LD50sa | Septicemic plague LD50sa | Pneumonic plague LD50sa | Reference |
|---|---|---|---|---|
| Parent strain | 25 | <14 | 329 | 8, 55 |
| Fe transport mutants | ||||
| Psn (Fe3+-Ybt uptake) | >2.6 × 107 (>1.13 × 106-fold) | <14 | 1.1 × 104 (33-fold) | 8, 55 |
| irp2 (Ybt synthesis) | >1.3 × 107 (>5.2 × 105-fold) | ∼48 | 2.6 × 105 (790-fold) | 8, 55 |
| ΔfeoB (Fe2+ uptake) | 55 (NS) | Not tested | 211 (NS) | 26 |
| ΔyfeAB (Fe & Mn uptake) | 205 (9-fold; NS) 74.3 (8-fold) | Not tested | 139 (NS) | 24, 26 |
| ΔyfeAB ΔfeoB (Fe2+ & Mn uptake) | 2,035 (89-fold) | Not tested | 407 (NS) | 26 |
| Δpgm (Ybt-Fet-Flp-; Fe3+-Ybt & Fe2+uptake) | > 107 | < 6 (NS)b | >3.9 × 106 (>1.2 × 104-fold) | 8, 22, 55 |
| Δpgm ΔyfeAB (Ybt- Fet-Flp-; Fe3+ & Fe2+uptake) | Not tested | > 1.7 × 107b (>1.2 × 106-fold) | Not tested | 22 |
| ΔhmuP'RSTUV Delta;hasRADE (heme uptake) | <4.2 (NS) | Not tested | 273 (NS)c | 20 (unpublished) |
| Mn transport mutants | ||||
| ΔmntH (Mn uptake) | 36 (delayed TTD) | Not tested | Not tested | 11 |
| ΔyfeAB ΔmntH (Mn & Feuptake) | 3,068 (133-fold) | Not tested | 142 (NS) | 11 |
| Zn transport mutants | ||||
| znu (Zn uptake) | 266 ± 149 (NS)d | ∼11 ± 5 | 1,113 ± 1,376 (NS)d | 8, 60 |
| psn ΔznuBC (Fe3+-Ybt & Zn uptake) | Not tested | ∼40 (delayed TTD) | Not tested | 8 |
| irp2 znu (Ybt synthesis & Zn uptake) | Not tested | ∼6.0 × 106 (>4.3 × 105-fold) | Not tested | 8 |
| Δpgm znu (Ybt- Fet-Flp-; Fe3+, Fe2+ & Zn uptake) | Not tested | 5.7 × 106 (>9.5 × 105-fold) | Not tested | 8 |
All studies used outbred Swiss Webster mice. Bubonic plague – subcutaneous injection; Septicemic plague – retro-orbital injection; Pneumonic plague – intranasal instillation; delayed TTD – delayed time-to-death at low doses compared to parent/wild-type strain except for the psn ΔznuBC mutant which was compared to the znu mutant. NS – not significantly different from the wild-type strain.
The Δpgm and Δpgm ΔyfeAB mutants have a jopJ∷Mud Δpsa background. A combination of ΔyfeAB and genes encoded within the pgm locus could contribute to the large virulence loss in the Δpgm ΔyfeAB mutant.
Unpublished data – Swiss Webster mice were infected by intranasal instillation with Y. pestis cells grown as described in other studies on pneumonic plague. All mouse experiments in Table 2 were conducted in accordance with the Animal Welfare Act and approved by the University of Kentucky Institutional Animal Care and Use Committee.
Standard deviations are shown only for the znu mutant because of high variations. For clarity, standard deviations are not show for all other mutants tested.