Induction of β-Lactamase Activity and Decreased β-Lactam Susceptibility by CO in Clinical Bacterial Isolates.

Antimicrobial susceptibility testing of clinical isolates is a crucial step toward appropriate treatment of infectious diseases. The clinical isolate 14IUHPL001, recently isolated from a 63-year-old woman with atypical pneumonia, featured decreased susceptibility to β-lactam antibiotics when cultivated in 5% CO. Quantitative β-lactamase assays demonstrated a significant ( < 0.0001) increase in enzymatic activity between bacteria cultivated in 5% CO over those incubated in ambient air. The presence of β-lactamase genes and was detected in the clinical isolate 14IUHPL001 by PCR, and the genes were positively identified by nucleotide sequencing. Expression of and was detected by reverse transcription-PCR during growth at 5% CO but not during growth in ambient air. A statistically significant alkaline shift was observed following cultivation of 14IUHPL001 in both ambient air and 5% CO, allowing desegregation of the previously reported effects of acidic pH from the currently reported effect of 5% CO on and β-lactamases. To ensure that the observed phenomenon was not unique to , we evaluated a clinical isolate of -carrying and found parallel induction of gene expression and β-lactamase activity at 5% CO relative to ambient air. β-Lactamase induction and concurrent β-lactam resistance in respiratory tract pathogens as a consequence of growth in a physiologically relevant level of CO are of clinical significance, particularly given the ubiquity of TEM and SHV β-lactamase genes in diverse bacterial pathogens. This is the first report of β-lactamase induction by 5% CO.