Resistance to a new catecholic cephem, BO-1341, in Pseudomonas aeruginosa PAO

Two distinct types of mutant resistant to the catecholic cephem BO-1341 were isolated spontaneously from Pseudomonas aeruginosa PAO2146: (i) a mutant (CCB5-type) which produced beta-lactamase constitutively, and which appeared to result from a mutation in the regulatory gene (blaI at 41 min) controlling the structural gene (blaP at 25 min); (ii) a mutant (CCB7-type) with specific resistance to BO-1341. Induction of beta-lactamase production in strain CCB7 by BO-1341 was diminished markedly when compared with that in the parent strain. This was not the case for ceftazidime or cefoxitin, suggesting impaired uptake of BO-1341 as an explanation for the resistance. Electrophoretic analysis demonstrated increased production of a 55 kDa protein in the periplasmic space and a 84 kDa outer membrane protein. These data suggested that specific resistance to BO-1341 might involve quantitative alterations in the composition of the outer membrane and periplasmic proteins.