Adaptive resistance to the hydrophobic antibiotic novobiocin in Pasteurella multocida
General Material Designation
[Thesis]
First Statement of Responsibility
M. Arif
Subsequent Statement of Responsibility
F. R. Champlin
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
Mississippi State University
Date of Publication, Distribution, etc.
1997
PHYSICAL DESCRIPTION
Specific Material Designation and Extent of Item
56
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
M.S.
Body granting the degree
Mississippi State University
Text preceding or following the note
1997
SUMMARY OR ABSTRACT
Text of Note
Naturally-occurring strains of Pasteurella multocida are atypically susceptible to hydrophobic antibiotics such as novobiocin, despite their typical gram-negative cell envelope ultrastructure. The goal of the present study was to develop a novobiocin resistance model system consisting of parental, adaptively resistant, and deadapted strains of P. multocida. By cultivating two serotype A encapsulated and two nonencapsulated cell surface hydrophobicity variants in the presence of sublethal novobiocin concentrations and sequentially subculturing them in the presence of increasing antibiotic concentrations, four strains were derived which were adaptively resistant to 1000mug/ml of novobiocin. Cross resistance studies revealed the acquisition of novobiocin resistance to be accompanied by a concomitant acquisition of resistance to coumermycin, an antibiotic which shares the DNA gyrase mechanistic target with novobiocin, but not to the functionally disparate antibiotic rifamycin. Acquisition of adaptive resistance in the encapsulated parental strains also occurred concomitantly with a loss of the ability to synthesize capsular material as assessed microscopically with the aid of a polysaccharide-specific, congo red-acid fuchsin staining procedure. A hydrocarbon adherence assay revealed that removal of capsular material from encapsulated parental strains was followed by a concomitant increase in overall cell surface hydrophobicity, while the hydrophobicity values for nonencapsulated parental strains remained essentially the same after both adaptation and deadaptation. Qualitative thin layer chromatography did not reveal detectable changes in overall cell envelope lipid composition in the adaptive resistance model systems. These data suggest that adaptive resistance to novobiocin acquired in this manner is stable, and therefore genotypic rather than physiologic in nature. (Abstract shortened by UMI.)