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Ever-Adapting RND Efflux Pumps in Gram-Negative Multidrug-Resistant Pathogens: A Race against Time

RND Efflux Systems Contribute to Resistance and Virulence of Aliarcobacter butzleri

CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal
National Reference Laboratory for Gastrointestinal Infections, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, Av. Padre Cruz, 1649-016 Lisbon, Portugal
Author to whom correspondence should be addressed.
Academic Editors: Isabelle Broutin, Attilio V Vargiu, Henrietta Venter and Gilles Phan
Received: 31 May 2021 / Revised: 1 July 2021 / Accepted: 5 July 2021 / Published: 6 July 2021
Aliarcobacter butzleri is an emergent enteropathogen that can be found in a range of environments. This bacterium presents a vast repertoire of efflux pumps, such as the ones belonging to the resistance nodulation cell division family, which may be associated with bacterial resistance, as well as virulence. Thus, this work aimed to evaluate the contribution of three RND efflux systems, AreABC, AreDEF and AreGHI, in the resistance and virulence of A. butzleri. Mutant strains were constructed by inactivation of the gene that encodes the inner membrane protein of these systems. The bacterial resistance profile of parental and mutant strains to several antimicrobials was assessed, as was the intracellular accumulation of the ethidium bromide dye. Regarding bacterial virulence, the role of these three efflux pumps on growth, strain fitness, motility, biofilm formation ability, survival in adverse conditions (oxidative stress and bile salts) and human serum and in vitro adhesion and invasion to Caco-2 cells was evaluated. We observed that the mutants from the three efflux pumps were more susceptible to several classes of antimicrobials than the parental strain and presented an increase in the accumulation of ethidium bromide, indicating a potential role of the efflux pumps in the extrusion of antimicrobials. The mutant strains had no bacterial growth defects; nonetheless, they presented a reduction in relative fitness. For the three mutants, an increase in the susceptibility to oxidative stress was observed, while only the mutant for AreGHI efflux pump showed a relevant role in bile stress survival. All the mutant strains showed an impairment in biofilm formation ability, were more susceptible to human serum and were less adherent to intestinal epithelial cells. Overall, the results support the contribution of the efflux pumps AreABC, AreDEF and AreGHI of A. butzleri to antimicrobial resistance, as well as to bacterial virulence. View Full-Text
Keywords: Aliarcobacter butzleri; RND efflux pumps; virulence; resistance Aliarcobacter butzleri; RND efflux pumps; virulence; resistance
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MDPI and ACS Style

Mateus, C.; Nunes, A.R.; Oleastro, M.; Domingues, F.; Ferreira, S. RND Efflux Systems Contribute to Resistance and Virulence of Aliarcobacter butzleri. Antibiotics 2021, 10, 823.

AMA Style

Mateus C, Nunes AR, Oleastro M, Domingues F, Ferreira S. RND Efflux Systems Contribute to Resistance and Virulence of Aliarcobacter butzleri. Antibiotics. 2021; 10(7):823.

Chicago/Turabian Style

Mateus, Cristiana, Ana R. Nunes, Mónica Oleastro, Fernanda Domingues, and Susana Ferreira. 2021. "RND Efflux Systems Contribute to Resistance and Virulence of Aliarcobacter butzleri" Antibiotics 10, no. 7: 823.

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