PENICILLIN-BINDING PROTEINS OF RHODOCOCCUS-EQUI - POTENTIAL ROLE IN RESISTANCE TO IMIPENEM

Rhodococcus equi is a gram-positive coccobacillus which, like other me mbers of the order Actinomycetales, is increasingly reported as an opp ortunistic pathogen in patients with AIDS. The use of combinations of antibiotics that include imipenem (IMP) has been suggested for the tre atment of patients infected with R. equi. An antagonism between IMP, m eropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin and other beta-lactams, such as penicillin, amoxicillin, cephalothin, and ticarc illin, was detected in vitro both on Mueller-Hinton agar and in broth for all 10 IMP-susceptible R. equi strains examined. To study the mech anism of the antagonism between beta-lactams, a mutant with decreased susceptibility to IMP (isolate IpR) was selected in vitro from a susce ptible clinical isolate of R. equi (isolate IpS). IpR exhibited decrea sed susceptibility to IMP, meropenem, cefoxitin, ceftriaxone, moxalact am, and oxacillin but not to penicillin, amoxicillin, cephalothin, or ticarcillin. No beta-lactamase was found in IpS, IpS cultured with ant agonistic beta-lactams, or IpR strains. Labeling of penicillin-binding proteins (PBPs) revealed four PBPs with molecular masses of ca. 59, 5 6, 43, and 26 kDa in IpS. In IpR, PBP 3 disappeared and was replaced b y PBP 3a of 40 kDa. The 50% saturation of PBP 3 and PBP 3a by the carb apenems correlated with the MICs of these antibiotics, respectively, f or IpS and IpR strains. However, PBP 3a was not detected in IpS when I pS was cultured in the presence of 13-lactams, with which antagonism w as observed. The present work describes the PBPs of R. equi and report s that IMP resistance in R. equi is related to an altered PBP pattern.