Characterization of RaeE-RaeF-RopN, a putative RND efflux pump system in Riemerella anatipestifer

The emergence and transmission of novel antimicrobial resistance genes pose a great threat to public health globally. Recently, the plasmid-encoding RND efflux pump TMexCD1-TOprJ1 in Klebsiella pneumoniae was reported to reduce the sensitivity of multiple antimicrobials. Herein, we identified a pandrug-resistant Proteus mirabilis isolate, which harbored the novel tmexCD3-toprJ3 gene cluster located on SXT/R391 ICE. This study expands current knowledge in transfer mechanism of tmexCD1-toprJ1-like gene clusters among P. mirabilis and warrant further genomic epidemiology investigations.

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Screening of Natural Products and Derivatives for the Identification of RND Efflux Pump Inhibitors

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207319666160720101502 ◽

2016 ◽

Vol 19 (9) ◽

pp. 705-713 ◽

Cited By ~ 9

Author(s):

Debarati Choudhury ◽

Anupam Talukdar ◽

Pankaj Chetia ◽

Amitabha Bhattacharjee ◽

Manabendra Choudhury

Keyword(s):

Natural Products ◽

Efflux Pump ◽

Rnd Efflux Pump ◽

Efflux Pump Inhibitors

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New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action

Antibiotics ◽

10.3390/antibiotics10060709 ◽

2021 ◽

Vol 10 (6) ◽

pp. 709

Author(s):

Marta Jorba ◽

Marina Pedrola ◽

Ouldouz Ghashghaei ◽

Rocío Herráez ◽

Lluis Campos-Vicens ◽

...

Keyword(s):

Inhibitory Concentration ◽

Efflux Pump ◽

Synergistic Effects ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Detailed Characterization ◽

Low Concentrations ◽

Pump Activity ◽

Bacteriological Evaluation ◽

Kinetics Of

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported.

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Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

BMC Microbiology ◽

10.1186/s12866-021-02250-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixing Liu ◽

Renchi Fang ◽

Ying Zhang ◽

Lijiang Chen ◽

Na Huang ◽

...

Keyword(s):

Lipid A ◽

Efflux Pump ◽

Resistance Mechanism ◽

Carbapenem Resistance ◽

Enterobacter Cloacae ◽

Resistance Mechanisms ◽

Colistin Resistance ◽

Carbapenem Resistant ◽

Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00456-12 ◽

2012 ◽

Vol 56 (8) ◽

pp. 4450-4458 ◽

Cited By ~ 59

Author(s):

Mark Veleba ◽

Paul G. Higgins ◽

Gerardo Gonzalez ◽

Harald Seifert ◽

Thamarai Schneiders

Keyword(s):

Multidrug Resistance ◽

Klebsiella Pneumoniae ◽

Efflux Pump ◽

Content Type ◽

Resistance Phenotype ◽

Serratia Proteamaculans ◽

Virulence Potential ◽

Article Type ◽

Acrab Efflux Pump

ABSTRACTTranscriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes.Klebsiella pneumoniaeis a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription oframAis associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466–4467, 2012). Bioinformatic analyses of the availableKlebsiellagenome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded inK. pneumoniae,Enterobactersp. 638,Serratia proteamaculans568, andEnterobacter cloacae. We show that the overexpression ofrarAresults in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show thatrarA(MGH 78578 KPN_02968) and its neighboring efflux pump operonoqxAB(KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest thatrarAoverexpression upregulates theoqxABefflux pump. Additionally, it appears thatoqxR, encoding a GntR-type regulator adjacent to theoqxABoperon, is able to downregulate the expression of theoqxABefflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.

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FarRRegulates the farAB-Encoded Efflux Pump of Neisseriagonorrhoeae via an MtrR RegulatoryMechanism

Journal of Bacteriology ◽

10.1128/jb.185.24.7145-7152.2003 ◽

2003 ◽

Vol 185 (24) ◽

pp. 7145-7152 ◽

Cited By ~ 53

Author(s):

E.-H. Lee ◽

C. Rouquette-Loughlin ◽

J. P. Folster ◽

W. M. Shafer

Keyword(s):

Regulatory Mechanism ◽

Efflux Pump ◽

Regulatory Protein ◽

Transcriptional Repressors ◽

Sequence Database ◽

Mobility Shift ◽

Pump System ◽

Regulatory Cascade ◽

Genome Sequence Database ◽

Gel Mobility Shift

ABSTRACT The farAB operon of Neisseria gonorrhoeae encodes an efflux pump which mediates gonococcal resistance to antibacterial fatty acids. It was previously observed that expression of the farAB operon was positively regulated by MtrR, which is a repressor of the mtrCDE-encoded efflux pump system (E.-H. Lee and W. M. Shafer, Mol. Microbiol. 33:839-845, 1999). This regulation was believed to be indirect since MtrR did not bind to the farAB promoter. In this study, computer analysis of the gonococcal genome sequence database, lacZ reporter fusions, and gel mobility shift assays were used to elucidate the regulatory mechanism by which expression of the farAB operon is modulated by MtrR in gonococci. We identified a regulatory protein belonging to the MarR family of transcriptional repressors and found that it negatively controls expression of farAB by directly binding to the farAB promoter. We designated this regulator FarR to signify its role in regulating the farAB operon. We found that MtrR binds to the farR promoter, thereby repressing farR expression. Hence, MtrR regulates farAB in a positive fashion by modulating farR expression. This MtrR regulatory cascade seems to play an important role in adjusting levels of the FarAB and MtrCDE efflux pumps to prevent their excess expression in gonococci.

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