scholarly journals Identification of binding residues between periplasmic adapter protein (PAP) and RND efflux pumps explains PAP-pump promiscuity and roles in antimicrobial resistance

2019 ◽  
Vol 15 (12) ◽  
pp. e1008101 ◽  
Author(s):  
Helen E. McNeil ◽  
Ilyas Alav ◽  
Ricardo Corona Torres ◽  
Amanda E. Rossiter ◽  
Eve Laycock ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Efflux Pumps ◽  
Adapter Protein ◽  
Rnd Efflux Pumps ◽  
Binding Residues

scholarly journals Multidrug Resistance Efflux Pumps in Acinetobacter spp.: An Update

2021 ◽  
Author(s):  
Vanessa Kornelsen ◽  
Ayush Kumar
Keyword(s):  
Multidrug Resistance ◽  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
Clinical Importance ◽  
Efflux Pumps ◽  
Major Facilitator Superfamily ◽  
Small Multidrug Resistance ◽  
Resistance Nodulation Division ◽  
Rnd Efflux Pumps ◽  
Major Facilitator

Acinetobacter spp. have become of increased clinical importance as studies have shown the antimicrobial resistant potential of these species. Efflux pumps can lead to reduced susceptibility to a variety of antibiotics and are present in large number across Acinetobacter spp. There are six families of efflux pumps that have been shown to be of clinical relevance: the Major Facilitator Superfamily (MFS), Small Multidrug Resistance (SMR) family, ATP-binding cassette (ABC) family, Multidrug and Toxic Compound Extrusion (MATE) family, Proteobacterial Antimicrobial Compound Efflux (PACE) family and Resistance-Nodulation-Division (RND) family. A lot of work has been done on understanding and characterizing the roles that these efflux pumps play in relation to antimicrobial resistance and the physiology of these bacteria. RND efflux pumps, with their expansive substrate profiles, are a major component of Acinetobacter spp. antimicrobial resistance. New discoveries over the last decade have shed a lot of light on to the complex regulation of these efflux pumps leading to greater understanding and potential of slowing the reduced susceptibility seen by these bacterial species.

scholarly journals Interplay between Two RND Systems Mediating Antimicrobial Resistance in Brucella suis

2009 ◽  
Vol 191 (8) ◽  
pp. 2530-2540 ◽  
Author(s):  
Fernando A. Martin ◽  
Diana M. Posadas ◽  
Mariela C. Carrica ◽  
Silvio L. Cravero ◽  
David O'Callaghan ◽  
...  
Keyword(s):  
Crystal Violet ◽  
Pathogenic Bacteria ◽  
Regulatory Protein ◽  
Efflux Pumps ◽  
Reading Frame ◽  
Membrane Fusion Protein ◽  
Physiological Processes ◽  
Defective Mutant ◽  
Brucella Suis ◽  
Rnd Efflux Pumps

ABSTRACT The RND-type efflux pumps are responsible for the multidrug resistance phenotype observed in many clinically relevant species. Also, RND pumps have been implicated in physiological processes, with roles in the virulence mechanisms of several pathogenic bacteria. We have previously shown that the BepC outer membrane factor of Brucella suis is involved in the efflux of diverse drugs, probably as part of a tripartite complex with an inner membrane translocase. In the present work, we characterize two membrane fusion protein-RND translocases of B. suis encoded by the bepDE and bepFG loci. MIC assays showed that the B. suis ΔbepE mutant was more sensitive to deoxycholate (DOC), ethidium bromide, and crystal violet. Furthermore, multicopy bepDE increased resistance to DOC and crystal violet and also to other drugs, including ampicillin, norfloxacin, ciprofloxacin, tetracycline, and doxycycline. In contrast to the ΔbepE mutant, the resistance profile of B. suis remained unaltered when the other RND gene (bepG) was deleted. However, the ΔbepE ΔbepG double mutant showed a more severe phenotype than the ΔbepE mutant, indicating that BepFG also contributes to drug resistance. An open reading frame (bepR) coding for a putative regulatory protein of the TetR family was found upstream of the bepDE locus. BepR strongly repressed the activity of the bepDE promoter, but DOC released the repression mediated by BepR. A clear induction of the bepFG promoter activity was observed only in the BepDE-defective mutant, indicating a regulatory interplay between the two RND efflux pumps. Although only the BepFG-defective mutant showed a moderate attenuation in model cells, the activities of both bepDE and bepFG promoters were induced in the intracellular environment of HeLa cells. Our results show that B. suis harbors two functional RND efflux pumps that may contribute to virulence.

Efflux Pumps in Neisseria gonorrhoeae: Contributions to Antimicrobial Resistance and Virulence

2016 ◽  
pp. 439-469 ◽  
Author(s):  
William M. Shafer ◽  
Edward W. Yu ◽  
Corinne Rouquette-Loughlin ◽  
Daniel Golparian ◽  
Ann E. Jerse ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Efflux Pumps

scholarly journals Landscape of Resistance-Nodulation-Cell Division (RND)-Type Efflux Pumps in Enterobacter cloacae Complex

2016 ◽  
Vol 60 (4) ◽  
pp. 2373-2382 ◽  
Author(s):  
François Guérin ◽  
Claire Lallement ◽  
Christophe Isnard ◽  
Anne Dhalluin ◽  
Vincent Cattoir ◽  
...  
Keyword(s):  
Cell Division ◽  
Antimicrobial Resistance ◽  
Galleria Mellonella ◽  
Acquired Resistance ◽  
Enterobacter Cloacae ◽  
Efflux Pumps ◽  
Wild Type ◽  
Content Type ◽  
Active Efflux

ABSTRACTIn Gram-negative bacteria, the active efflux is an important mechanism of antimicrobial resistance, but little is known about theEnterobacter cloacaecomplex (ECC). It is mediated primarily by pumps belonging to the RND (resistance-nodulation-cell division) family, and only AcrB, part of the AcrAB-TolC tripartite system, was characterized in ECC. However, detailed genome sequence analysis of the strainE. cloacaesubsp.cloacaeATCC 13047 revealed to us that 10 other genes putatively coded for RND-type transporters. We then characterized the role of all of these candidates by construction of corresponding deletion mutants, which were tested for their antimicrobial susceptibility to 36 compounds, their virulence in the invertebrateGalleria mellonellamodel of infection, and their ability to form biofilm. Only the ΔacrBmutant displayed significantly different phenotypes compared to that of the wild-type strain: 4- to 32-fold decrease of MICs of several antibiotics, antiseptics, and dyes, increased production of biofilm, and attenuated virulence inG. mellonella. In order to identify specific substrates of each pump, we individually expressed intransall operons containing an RND pump-encoding gene into the ΔacrBhypersusceptible strain. We showed that three other RND-type efflux systems (ECL_00053-00055, ECL_01758-01759, and ECL_02124-02125) were able to partially restore the wild-type phenotype and to superadd to and even enlarge the broad range of antimicrobial resistance. This is the first global study assessing the role of all RND efflux pumps chromosomally encoded by the ECC, which confirms the major role of AcrB in both pathogenicity and resistance and the potential involvement of other RND-type members in acquired resistance.

scholarly journals Molecular characterization of antimicrobial resistance in non-typhoidal salmonellae associated with systemic manifestations from India

2010 ◽  
Vol 59 (12) ◽  
pp. 1477-1483 ◽  
Author(s):  
G. A. Menezes ◽  
M. A. Khan ◽  
B. N. Harish ◽  
S. C. Parija ◽  
W. Goessens ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Antimicrobial Susceptibility ◽  
Pcr Amplification ◽  
Efflux Pumps ◽  
Resistance Mutations ◽  
Pcr Screening ◽  
Extended Spectrum ◽  
Class 1 ◽  
Screening And Identification ◽  
Systemic Manifestations

Extended-spectrum cephalosporins and fluoroquinolones are essential antimicrobials for treating invasive salmonellosis, although emerging resistance to these antimicrobials is of growing concern, especially in India. Therefore, a study was conducted to characterize the antimicrobial susceptibility phenotypes, types of extended-spectrum β-lactamase (ESBL) gene plasmids and serological relationships of 21 non-typhoidal Salmonella isolates from patients who attended three different hospitals in India from 2006 to 2008. The isolates were cultured from stool, blood and cerebrospinal fluid samples obtained from patients presenting with diarrhoea and accompanying systemic manifestations such as fever, vomiting and meningism. Non-typhoidal Salmonella isolates were investigated using serotyping and antimicrobial susceptibility testing. PCR screening was also performed to detect the β-lactamase, qnr and aac(6′)-Ib-cr genes and class 1 integrons. Sequencing for quinolone resistance mutations and plasmid replicon typing were also performed. An antimicrobial resistance microarray was used for preliminary screening and identification of bla TEM and bla SHV genes, and phenotypic testing for the presence of efflux pumps was also performed. Ten out of 21 isolates (48 %) possessed the extended-spectrum cephalosporin resistance phenotype, with PCR amplification and sequencing revealing that isolates possessed TEM-1, SHV-12, DHA-1, OXA-1-like and CTX-M-15 ESBL genes. FIIs plasmid replicons were detected in seven isolates (33 %). The involvement of efflux pumps was detected in four isolates (19 %) resistant to ciprofloxacin. It was concluded that SHV-12-carrying Salmonella serotype Agona may play an important role in ESBL-mediated resistance in non-typhoidal salmonellae in India. The very high percentage (48 %) of ESBL-producing non-typhoidal salmonellae isolated from these patients represents a real and immediate challenge to the effective antimicrobial therapy of Salmonella infections associated with systemic manifestations. Continued surveillance for the presence of ESBL-producing (non-typhoidal) salmonellae in India is essential.

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