Discovery of new antimicrobial resistance gene
Identification of a novel metallo-β-lactamase, CAM-1, in clinical Pseudomonas aeruginosa isolates from Canada. Boyd DA*, Lisboa LF, Rennie R, Zhanel GG, Dingle TC, Mulvey MR*. J Antimicrob Chemother 2019 Jun 1; 74(6):1563-7. doi: https://doi.org/10.1093/jac/dkz066
This science story explains the collaborative work to identify and study a novel gene causing antimicrobial resistance (AMR). This work is one example of global public health efforts to better understand, and therefore address AMR. The public health threat of AMR is also the topic of a spotlight report recently issued by Canada’s Chief Public Health Officer.
What was known about this area prior to your work, and why was the research done?
Pseudomonas aeruginosa (P. aeruginosa) causes infections in healthcare settings among critically ill and immunocompromised people. Antibiotics, such as the carbapenem class of drugs, are typically used to treat infections caused by P. aeruginosa. However, P. aeruginosa has been found to rapidly and frequently develop antibiotic resistance to these last-line antibiotics. This study examines a small group of carbapenem-resistant P. aeruginosa isolates that have a novel bacterial enzyme which renders carbapenem drugs ineffective. The isolates did not have any of the most common globally distributed carbapenemase genes. This highlights the need to expand testing beyond standard molecular assays.
What are your most significant findings from this work?
Whole genome sequencing (WGS) methods were used to characterize the P. aeruginosa isolates and bioinformatic analysis was done to identify the potential genome section responsible for the observed antibiotic resistance. The novel class B β-lactamase gene, blaCAM-1 (Central Alberta Metallo-β-lactamase) was found within a section of the genome that can be easily transferred to other bacteria. This method of sharing genes is one way AMR spreads to other strains. However, experiments showed this novel gene could not be transferred between strains. The drug resistance was identified by standard laboratory growth tests but required complex genome analysis to pinpoint the specific gene responsible for drug resistance.
What are the implications or impact of the research?
This study adds important knowledge to the tools and mechanisms used by bacteria to survive under antimicrobial stress, thereby developing resistance. Simple phenotypic tests can confirm carbapenemase production and antibiotic resistance. This is important as some drug-resistant strains may not be identified by standard tests that are specific to the presence of the most common resistance genes. In the spirit of open data, the novel gene sequence identified in this study has been added to publicly available AMR databases.
Additional References of Significance:
- Mataseje LF*, Bryce E, Roscoe D, Boyd DA*, Embree J, Gravel D, Katz, K, Kibsey P, Kuhn M, Mounchili A, Simor A, Taylor G, Turgeon N, Mulvey MR*. Carbapenem-resistant Gram negative bacilli in Canada 2009-10: results from the Canadian Nosocomial Infection Surveillance Program (CNISP). J Antimicrob Chemother 2012 Jun; 67(6):1359-67. doi: https://doi.org/10.1093/jac/dks046
- Mataseje LF*, Abdesselam K, Vachon J, Mitchel R, Bryce E, Roscoe D, Boyd DA*, Embree J, Katz K, Kibsey P, Simor AE, Taylor G, Turgeon N, Langley J, Gravel D, Amaratunga K, Mulvey MR*. Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing Enterobacteriaceae, 2010 to 2014. Antimicrob Agents Chemother 2016 Oct 21; 60(11):6787-94. doi: https://doi.org/10.1128/AAC.01359-16
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