Combinations of mutations inenvZ,ftsI,mrdA,acrBandacrRcan cause high-level carbapenem resistance inEscherichia coli

• DOI: 10.1093/jac/dkv475
• Publication Date: 2016-02-12T04:40:43Z
• Authors: Marlen Adler; Mehreen Anjum; Dan I. Andersson; Linus Sandegren
• Keywords: Ertapenem; Carbapenem

The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use carbapenems, the group β-lactams with broadest spectrum activity. Bacterial resistance carbapenems is mainly due acquired carbapenemases or a combination ESBL production and reduced drug influx via loss outer-membrane porins. Here, we have studied development carbapenem in Escherichia coli absence β-lactamases.We selected mutants high-level through repeated serial passage presence increasing concentrations meropenem ertapenem for ∼60 generations. Isolated clones were whole-genome sequenced, order which identified mutations arose was determined passaged populations. Key reconstructed, bacterial growth rates populations isolated levels 23 antibiotics measured.High-level resulted from downstream effects envZ mutation target AcrAB-TolC-mediated export, together PBP genes [mrdA (PBP2) after exposure ftsI (PBP3) exposure].Our results show that antibiotic evolution can occur several parallel pathways new mechanisms may appear most common (i.e. β-lactamases porins) been eliminated. These findings suggest strategies commonly observed might be hampered by appearance previously unknown resistance.