AI Article Synopsis
- * Whole-genome sequencing identified that the strain belonged to sequence type ST274 and featured significant genetic mutations, including a nonsense mutation affecting the carbapenem porin OprD and alterations in the efflux pump regulator NfxB and MexD.
- * Research using mutant strains showed that these genetic changes led to the resistance against novel cephalosporin-β-lactamase inhibitors due to a modification in the substrate specificity of the MexD
Article Abstract
A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. Through the construction of mutants and complementation assays with wild-type , it was evidenced that resistance to the novel cephalosporin-β-lactamase inhibitor combinations was caused by the modification of MexD substrate specificity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284450 | PMC |
| http://dx.doi.org/10.1128/AAC.00089-21 | DOI Listing |
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