Artículo
Disbalancing Envelope Stress Responses as a Strategy for Sensitization of Escherichia coli to Antimicrobial Agents
Autor/es | Recacha Villamor, Esther
Fox, Valeria Díaz Díaz, Sara García Duque, Ana Docobo Pérez, Fernando Pascual Hernández, Álvaro Rodríguez Martínez, José Manuel |
Departamento | Universidad de Sevilla. Departamento de Microbiología |
Fecha de publicación | 2021 |
Fecha de depósito | 2022-03-29 |
Publicado en |
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Resumen | Disbalancing envelope stress responses was investigated as a strategy for sensitization of Escherichia coli to antimicrobial agents. Seventeen isogenic strains were selected from the KEIO collection with deletions in genes ... Disbalancing envelope stress responses was investigated as a strategy for sensitization of Escherichia coli to antimicrobial agents. Seventeen isogenic strains were selected from the KEIO collection with deletions in genes corresponding to the σE, Cpx, Rcs, Bae, and Psp responses. Antimicrobial activity against 20 drugs with different targets was evaluated by disk diffusion and gradient strip tests. Growth curves and time-kill curves were also determined for selected mutant-antimicrobial combinations. An increase in susceptibility to ampicillin, ceftazidime, cefepime, aztreonam, ertapenem, and fosfomycin was detected. Growth curves for Psp response mutants showed a decrease in optical density (OD) using sub-MIC concentrations of ceftazidime and aztreonam (ΔpspA and ΔpspB mutants), cefepime (ΔpspB and ΔpspC mutants) and ertapenem (ΔpspB mutant). Time-kill curves were also performed using 1xMIC concentrations of these antimicrobials. For ceftazidime, 2.9 log10 (ΔpspA mutant) and 0.9 log10 (ΔpspB mutant) decreases were observed at 24 and 8 h, respectively. For aztreonam, a decrease of 3.1 log10 (ΔpspA mutant) and 4 log1010 (ΔpspB mutant) was shown after 4–6 h. For cefepime, 4.2 log10 (ΔpspB mutant) and 2.6 log10 (ΔpspC mutant) decreases were observed at 8 and 4 h, respectively. For ertapenem, a decrease of up to 6 log10 (ΔpspB mutant) was observed at 24 h. A deficient Psp envelope stress response increased E. coli susceptibility to beta-lactam agents such as cefepime, ceftazidime, aztreonam and ertapenem. Its role in repairing extensive inner membrane disruptions makes this pathway essential to bacterial survival, so that disbalancing the Psp response could be an appropriate target for sensitization strategies. |
Agencias financiadoras | Ministerio de Economía y Competitividad (MINECO). España Instituto de Salud Carlos III Ministerio de Economia, Industria y Competitividad (MINECO). España |
Identificador del proyecto | PI14/00940, PI17/01501, PI20/00239, RD16/0016/0001, and REIPI RD16/0016/0009
REIPI RD12/0015 and RD16/0016 |
Cita | Recacha Villamor, E., Fox, V., Díaz Díaz, S., García Duque, A., Docobo Pérez, F., Pascual Hernández, Á. y Rodríguez Martínez, J.M. (2021). Disbalancing Envelope Stress Responses as a Strategy for Sensitization of Escherichia coli to Antimicrobial Agents. Frontiers in Microbiology, 12, 653479. |
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