The characteristics and expression of laboratory derived chloramphenicol (CM) resistance in P. aeruginosa were examined. Resistant strains exhibiting single cell resistance of 1.5 to 2 mg/mL were readily isolated following one passage in CM at 150 to 1000 (mu)g/mL. Isogenic strains, selected on CM at 150 and 500 (mu)g/mL were chosen for detailed study. Resistance was not a consequence of drug detoxification or altered sensitivity of the target site. The resistant strains exhibited unusual phenotypic properties including pronounced variations in growth rate, CM susceptibility and cell morphology as a function of the composition of the growth medium. Growth in CM also resulted in significant alterations in amino acid transport and respiratory capacity, the extent of which varied with the strain, the growth medium and the concentration of CM. These drug and medium-dependent alterations were determined to reside in an increased and highly specific requirement for Ca('2+), Mg('2+), Mn('2+) or Sr('2+). Manipulation of the divalent cation concentration of a variety of growth media resulted in dramatic alterations in growth rate, resistance and amino acid transport. Ca('2+) was significantly more effective than the latter three ions. The expression of native and plasmid-mediated CM resistance was also modified by the external concentration of divalent cations. In view of the nature and specificity of the cation requirement, it was concluded that (1) divalent cation-mediated alterations of outer membrane permeability are fundamental to the expression of native and acquired CM resistance in P. aeruginosa; (2) laboratory-derived CM resistance involves envelope changes, such that interaction with divalent cations promotes more effective exclusion of CM. The latter conclusion is supported by other divalent cation-dependent alterations in envelope function in the resistant strains.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.71859 |
| Date | January 1983 |
| Creators | Irvin, Jean E. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000183041, proquestno: AAINK66574, Theses scanned by UMI/ProQuest. |
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