Mutational basis of Meropenem resistance in Pseudomonas aeruginosa

About authors

Pirogov Russian National Research Medical University, Moscow, Russia

Ostrovityanova, 1, Moscow, 117997, Russia: Correspondence should be addressed: Igor V. Chebotar

About paper

Funding: the study was supported by the Russian Science Foundation (project No. 20-15-00235).

Acknowledgements: the authors thank the Center of Precision Genome Editing and Genetic Technologies for Biomedicine of the Pirogov Russian National Research Medical University for their advice on the research methods.

Author contribution: Chebotar IV — concept, manuscript writing; Bocharova YuA — methods, formal analysis; Chaplin AV — formal analysis of sequencing data; Savinova TA — formal analysis of sequencing data; Vasiliadis YuA — methods, sequencing; Mayansky NA — concept, manuscript editing.

Compliance with ethical standards: the study was performed in full compliance with the principles of the Declaration of Helsinki and the standards for handling opportunistic pathogens.

Received: 2022-11-25 Accepted: 2022-12-11 Published online: 2022-12-28
Fig. 1. The dynamics of P. aeruginosa propagation across the surface of semi-solid agar towards the higher concentrations of meropenem. The images were acquired after incubation for 48, 72, 96, 120, 144, 168, 192, 216, 240 h from the start of the experiment. The dashed lines refer to the boundaries which divide sectors А, B, C, D, E with various meropenem concentrations (0, 0,2, 20, 200, 2000 μg/mL, respectively) in the lower layer of solid growth medium (see Methods). Asterisk refers to the starting point (inoculation of the culture of P. aeruginosa ATCC 27853)
Fig. 2. Topology of P. aeruginosa clones on the surface of semi-solid agar with the increasing meropenem concentrations after 240 h of incubation. The numbers refer to meropenem MICs (μg/mL) of isolates collected from the sites designated with the numbers. White arrows demonstrate the oprD-L238P clone propagation, black arrows demonstrate the oprD-G307D clone propagation
Table 1.Genes and gene combinations where nonsynonymous mutations were found
Table 2.Meropenem resistant phenotypes of P. aeruginosa and genes that can possibly determine carbapenem resistance