Chromosomal Loci Associated with Antibiotic Hypersensitivity in Pulmonary Isolates of Pseudomonas aeruginosa

Abstract
492a and 492c were 2 strains of P. aeruginosa isolated from the sputum of a patient with cystic fibrosis. The strains were closely related but expressed different antibiograms. 492c was hypersensitive (10-100 times more sensitive than 492a) to the .beta.-lactam antibiotics carbenicillin, methicillin, flucloxacillin, mecillinam and cefuroxime and the non-.beta.-lactam, nalidixic acid. 492c also showed enhanced sensitivity (4-8 times more sensitive than 492a) to chloroamphenicol, trimethoprim and novobiocin. 492a and PAO8 expressed similar levels of antibiotic resistance, except for trimethoprim, to which 492a was 5 times more sensitive than PAO8. Two genes associated with antibiotic hypersensitivity were mapped in the 30 min region of the chromosome, by means of R68.45-mediated plate matings between a Leu- mutant of 492c and PAO8, followed by transductional analysis using phage F116L. The first of these genes, blsA1, was closely linked to nalB, and in a PAO background was associated with hypersensitivity to the .beta.-lactams and a moderate increase in sensitivity to chloroamphenicol, trimethoprim, nalidixic acid and novobiocin. A further increase in sensitivity to the latter 3 antibiotics was associated with the 2nd gene, tpsA1, which mapped between ser-3 and hisV. This gene could also be transferred to PAO from 492a; thus 492c could have arisen from 492a in vivo following a single chromosomal mutation at the blsA locus. Isolation of a blsA mutant of PAO969 provided further evidence for this theory.