Role of efflux pumps in reduced susceptibility to tigecycline in Acinetobacter baumannii

Abstract

Acinetobacter baumannii is an important human pathogen responsible for a various type of infections. These bacterial strains are generally resistant to numerous antibiotics. Therefore, eradication of such strains is problematic and related to high mortality. We investigated the effect of cyanide 3-chlorophenylhydrazone (CCCP) efflux pump inhibitor in tigecycline-resistant strains of Acinetobacter baumannii. In a cross-sectional study, from July until the end of February 2017, eighty isolates of A. baumannii were recovered. Antimicrobial susceptibility testing against tigecycline was performed by the disc diffusion method and determination of minimum inhibitory concentration by broth microdilution method, according to Clinical and Laboratory Standards Institute guidelines. Active efflux pumps were detected by CCCP as an efflux pumps inhibitor, and the gene expression of some of the resistance/nodulation/division (RND)-type efflux pumps was measured by semiquantitative RT-PCR (qRT-PCR). Antibiotic susceptibility tests in this study showed that 78 of 80 A. baumannii isolates were resistant to tigecycline. The results of phenotypic detection of efflux pumps revealed that 23.07% of tigecycline-resistant A. baumannii isolates can contain active efflux pumps. On the basis of conventional PCR, genes coding for adeF and adeJ were detected in 76 (98%) A. baumannii isolates. The results of qRT-PCR showed that the transcript level of the adeJ gene increased in 66.6% A. baumannii isolates with CCCP-positive tests and was correlated with tigecycline resistance. The results of this study indicate that RND-type efflux pumps appear to play a significant role in the tigecycline resistance of A. baumannii.

Tetracycline resistance mediated by tet efflux pumps in clinical isolates of Acinetobacter baumannii

“…The results of the present study showed that the MIC for 43 of 47 tetracycline-resistant isolates (91.48%) was significantly reduced, by 4-16-fold in the presence of the efflux pump inhibitor. Similarly, Ardehali et al 27 found that CCCP reduced considerably the MIC of 51.25% of tigecycline-resistant A. baumannii isolates by 2-4-fold. The MICs of isolates resistant to minocycline, doxycycline, and tetracycline in the presence of different efflux pump inhibitors, such as CCCP, phenyl-arginine-β-naphthylamide, 1-(1-naphthylmethyl)-piperazine, reserpine, and verapamil were significantly reduced 28 .…”

<p>Evaluating the antimicrobial resistance patterns among major bacterial pathogens isolated from clinical specimens taken from patients in Mofid Children’s Hospital, Tehran, Iran: 2013–2018</p>

“…44 According to high antibiotic resistance among bacteria, in order to prevent undesirable effects of sepsis and septicemia, as well as in order to reduce the mortality rate due to these infections, precise detection and use of effective antibiotics for an efficient treatment are critical. 8,[45][46][47] Consequently, awareness of the antibiotic resistance patterns among common pathogens, holding workshops to correct prescription of empiric treatment, and changes in antimicrobial use are warranted and highly recommended. Finally, the results of DDM and MIC tests are of great importance, and individuals' free access to antibiotics should be prevented.…”

Efflux pump inhibitory activity of biologically synthesized silver nanoparticles against multidrug‐resistant Acinetobacter baumannii clinical isolates

“…are considered as the multidrug efflux pumps. In general, these efflux pumps can lead to the development of antibiotic‐resistant strains by decreasing the antibiotic concentration inside the cell [4–7]. AdeIJK , AdeABC , and AdeFGH are the most important efflux pumps known in A. baumanii , which belong to RND family [8].…”