title: Genetic Contexts of blaNDM-1 in Patients Carrying Multiple NDM-Producing Strains.
abstract: The carbapenem resistance determinant blaNDM-1 has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize the blaNDM-1 genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carry blaNDM-1 among the six different bacterial species isolated from the four patients. Two of these strains were novel Citrobacter freundii ST 20 and ST 21. The same IncN2-type blaNDM-1 genetic context was found in all four patients and within four different species. The IncA/C-type blaNDM-1 genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carrying blaNDM-1 for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms of blaNDM-1-related spread between bacterial species and genera via plasmids.
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia alexander.wailan@uqconnect.edu.au.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Wailan
authors.affiliation: Health Protection Branch, Department of Health, Queensland Government, Brisbane, Queensland, Australia.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Sartor
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia WHO Collaborating Centre for Infection Prevention and Control and GCC Center for Infection Control, Riyadh, Saudi Arabia.
authors.forename: Hosam M
authors.initials: HM
authors.lastname: Zowawi
authors.affiliation: Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: John D
authors.initials: JD
authors.lastname: Perry
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia Australian Infectious Diseases Research Centre, Brisbane, Australia Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia Pathology Queensland, Brisbane, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Sidjabat
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D010154:Pakistan; D010957:Plasmids / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D001618:beta-Lactamases; C552864:beta-lactamase NDM-1