Ampicillin resistance in Haemophilus influenzae: identification of resistance mechanisms.
The incidence and mechanisms of ampicillin resistance (MIC greater than 1 mg/l) were investigated in 105 clinical isolates of Haemophilus influenzae collected in Edinburgh during 1983/4. Fifteen (14.3%) ampicillin-resistant strains were identified and these were non-serotypable and comprised six biotypes. Isoelectric focusing and beta-lactamase-inhibition studies demonstrated that production of the TEM-1 beta-lactamase was the principal mechanism of resistance in nine (60%) strains. Radiolabelling revealed that one beta-lactamase-positive strain also had an unusual penicillin-binding protein (PBP) profit. No beta-lactamase activity was detected in the other six (40%) ampicillin-resistant strains. Two beta-lactamase-negative ampicillin-resistant strains had atypical PBP profiles. SDS-PAGE analysis showed that four beta-lactamase-negative ampicillin-resistant strains, including one with altered PBPs, exhibited outer membrane protein profiles which differed from those of sensitive strains of the same biotype. The ampicillin-resistance mechanism of the remaining strain could not be determined. Thus, several resistance mechanisms, either acting individually or in combination, are implicated in ampicillin resistance in H. influenzae.
D000667:Ampicillin / Q000494:pharmacology*; D000668:Ampicillin Resistance; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D002511:Cephalosporins / Q000494:pharmacology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology; D006602:Hexosyltransferases; D007525:Isoelectric Focusing; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D001618:beta-Lactamases / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D046915:Penicillin-Binding Proteins; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; C021720:nitrocefin