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32900.9582Effect of NlpE overproduction on multidrug resistance in Escherichia coli. NlpE, an outer membrane lipoprotein, functions during envelope stress responses in Gram-negative bacteria. In this study, we report that overproduction of NlpE increases multidrug and copper resistance through activation of the genes encoding the AcrD and MdtABC multidrug efflux pumps in Escherichia coli.201020211889
505010.9560Genomic Insights into Drug Resistance Determinants in Cedecea neteri, A Rare Opportunistic Pathogen. Cedecea, a genus in the Enterobacteriaceae family, includes several opportunistic pathogens reported to cause an array of sporadic acute infections, most notably of the lung and bloodstream. One species, Cedecea neteri, is associated with cases of bacteremia in immunocompromised hosts and has documented resistance to different antibiotics, including β-lactams and colistin. Despite the potential to inflict serious infections, knowledge about drug resistance determinants in Cedecea is limited. In this study, we utilized whole-genome sequence data available for three environmental strains (SSMD04, M006, ND14a) of C. neteri and various bioinformatics tools to analyze drug resistance genes in this bacterium. All three genomes harbor multiple chromosome-encoded β-lactamase genes. A deeper analysis of β-lactamase genes in SSMD04 revealed four metallo-β-lactamases, a novel variant, and a CMY/ACT-type AmpC putatively regulated by a divergently transcribed AmpR. Homologs of known resistance-nodulation-cell division (RND)-type multidrug efflux pumps such as OqxB, AcrB, AcrD, and MdtBC were also identified. Genomic island prediction for SSMD04 indicated that tolC, involved in drug and toxin export across the outer membrane of Gram-negative bacteria, was acquired by a transposase-mediated genetic transfer mechanism. Our study provides new insights into drug resistance mechanisms of an environmental microorganism capable of behaving as a clinically relevant opportunistic pathogen.202134442820
749020.9553Effect of Phorate on the Development of Hyperglycaemia in Mouse and Resistance Genes in Intestinal Microbiota. Phorate is a systemic, broad-spectrum organophosphorus insecticide. Although it is commonly used worldwide, phorate, like other pesticides, not only causes environmental pollution but also poses serious threats to human and animal health. Herein, we measured the blood glucose concentrations of high-fat-diet-fed mice exposed to various concentrations of phorate (0, 0.005, 0.05, or 0.5 mg/kg); we also assessed the blood glucose concentrations of high-fat-diet-fed mice exposed to phorate; we also assessed the distribution characteristics of the resistance genes in the intestinal microbiota of these mice. We found that 0.005 and 0.5 mg/kg of phorate induced obvious hyperglycaemia in the high-fat-diet-fed mice. Exposure to phorate markedly reduced the abundance of Akkermansia muciniphila in the mouse intestine. The resistance genes vanRG, tetW/N/W, acrD, and evgS were significantly upregulated in the test group compared with the control group. Efflux pumping was the primary mechanism of drug resistance in the Firmicutes, Proteobacteria, Bacteroidetes, Verrucomicrobia, Synergistetes, Spirochaetes, and Actinobacteria found in the mouse intestine. Our findings indicate that changes in the abundance of the intestinal microbiota are closely related to the presence of antibiotic-resistant bacteria in the intestinal tract and the metabolic health of the host.202236358236
774230.9553The dissimilarity of antibiotic and quorum sensing inhibitor on activated sludge nitrification system: Microbial communities and antibiotic resistance genes. Effects of antibiotics (azithromycin, AZM, 1-40 mg/L) and quorum sensing inhibitor (QSI, 2(5H)-furanone, 1-40 mg/L) combined pollution with environmental concentration of copper on bacterial/archaeal community and antibiotic resistance genes (ARGs) in activated sludge system were explored. QSI inhibited nitrification more obviously than AZM. AZM and QSI were synergistic inhibitions on bacterial diversity, and AZM inhibited bacterial compositions more than QSI. While, QSI had more impacts on archaeal diversity/compositions. Less interactions among bacteria and archaea communities with Aquimonas as keystone genus. Functional differences in bacteria/archaea communities were little, and AZM had more effects on metabolism. AZM mainly affected nitrifying bacteria (Candidatus Nitrospira nitrificans and Nitrosomonas). Specific denitrifying bacteria were enriched by AZM (Brevundimonas, 1.76-31.69%) and QSI (Comamonas, 0.61-9.61%), respectively. AZM enriched ARGs more easily than QSI and they were antagonistic to proliferation of ARGs. Bacteria were main hosts of ARGs (macrolide-lincosamide-streptogramin B, other/efflux, etc.) and archaea (Methanosphaerula, Methanolobus) carried multiple ARGs.202235306131
879840.9536Estrogen mimics induce genes encoding chemical efflux proteins in gram-negative bacteria. Escherichia coli and Pseudomonas aeruginosa are gram-negative bacteria found in wastewater and biosolids. Spanning the inner and outer membrane are resistance-nodulation-cell division superfamily (RND) efflux pumps responsible for detoxification of the cell, typically in response to antibiotics and other toxicity inducing substrates. Here, we show that estrogenic endocrine disruptors, common wastewater pollutants, induce genes encoding chemical efflux proteins. Bacteria were exposed to environmental concentrations of the synthetic estrogen 17α-ethynylestradiol, the surfactant nonylphenol, and the plasticizer bisphenol-A, and analyzed for RND gene expression via q-PCR. Results showed that the genes acrB and yhiV were over-expressed in response to the three chemicals in E. coli, and support previous findings that these two transporters export hormones. P. aeruginosa contains 12 RND efflux pumps, which were differentially expressed in response to the three chemicals: 17α-ethynylestradiol, bisphenol-A, and nonylphenol up-regulated mexD and mexF, while nonylphenol and bisphenol-A positively affected transcription of mexK, mexW, and triC. Gene expression via q-PCR of RND genes may be used to predict the interaction of estrogen mimics with RND genes. One bacterial response to estrogen mimic exposure is to induce gene expression of chemical efflux proteins, which leads to the expulsion of the contaminant from the cell.201525754012
618150.9534Two distinct major facilitator superfamily drug efflux pumps mediate chloramphenicol resistance in Streptomyces coelicolor. Chloramphenicol, florfenicol, and thiamphenicol are used as antibacterial drugs in clinical and veterinary medicine. Two efflux pumps of the major facilitator superfamily encoded by the cmlR1 and cmlR2 genes mediate resistance to these antibiotics in Streptomyces coelicolor, a close relative of Mycobacterium tuberculosis. The transcription of both genes was observed by reverse transcription-PCR. Disruption of cmlR1 decreased the chloramphenicol MIC 1.6-fold, while disruption of cmlR2 lowered the MIC 16-fold. The chloramphenicol MIC of wild-type S. coelicolor decreased fourfold and eightfold in the presence of reserpine and Phe-Arg-beta-naphthylamide, respectively. These compounds are known to potentiate the activity of some antibacterial drugs via efflux pump inhibition. While reserpine is known to potentiate drug activity against gram-positive bacteria, this is the first time that Phe-Arg-beta-naphthylamide has been shown to potentiate drug activity against a gram-positive bacterium.200919687245
524860.9533Antibiotic resistance of heterotrophic bacteria from the sediments of adjoining high Arctic fjords, Svalbard. Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) are now considered major global threats. The Kongsfjorden and Krossfjorden are the interlinked fjords in the Arctic that are currently experiencing the effects of climate change and receiving input of pollutants from distant and regional sources. The present study focused on understanding the prevalence of antibiotic resistance of retrievable heterotrophic bacteria from the sediments of adjacent Arctic fjords Kongsfjorden and Krossfjorden. A total of 237 bacterial isolates were tested against 16 different antibiotics. The higher resistance observed towards Extended Spectrum β-lactam antibiotic (ESBL) includes ceftazidime (45.56%) followed by trimethoprim (27%) and sulphamethizole (24.05%). The extent of resistance was meagre against tetracycline (2.53%) and gentamycin (2.95%). The 16S rRNA sequencing analysis identified that Proteobacteria (56%) were the dominant antibiotic resistant phyla, followed by Firmicutes (35%), Actinobacteria (8%) and Bacteroidetes. The dominant resistant bacterial isolates are Bacillus cereus (10%), followed by Alcaligenes faecalis (6.47%), Cytobacillus firmus (5.75%) Salinibacterium sp. (5%) and Marinobacter antarcticus (5%). Our study reveals the prevalence of antibiotic resistance showed significant differences in both the inner and outer fjords of Kongsfjorden and Krossfjorden (p < 0.05). This may be the input of antibiotic resistance bacteria released into the fjords from the preserved permafrost due to the melting of glaciers, horizontal gene transfer, and human influence in the Arctic region act as a selection pressure for the development and dissemination of more antibiotic resistant bacteria in Arctic fjords.202438767750
617470.9532Genetic Variability of the AcrAB-TolC Multidrug Efflux Pump Underlies SkQ1 Resistance in Gram-Negative Bacteria. SkQ1, a novel antibiotic targeting bacterial bioenergetics, is highly effective against both gram-positive and gram-negative bacteria. However, some gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, are highly resistant to it. In different gram-negative bacteria, this resistance is associated with the identity of their AcrB transporter protein sequence with the sequence of the AcrB protein from E. coli. SkQ1 is expelled from E. coli cells by the AcrAB-TolC multidrug efflux pump. In this study, we demonstrate that SkQ1 resistance in E. coli, in contrast to chloramphenicol resistance, does not depend on the presence of the multidrug efflux pump accessory protein AcrZ.201931993240
309380.9530Prevalence of antibiotic resistance and virulence genes in the biofilms from an aquifer recharged with stormwater. An improved understanding of the diversity and composition of microbial communities carrying antibiotic resistance genes (ARGs) and virulence genes (VGs) in aquifers recharged with stormwater is essential to comprehend potential human health risks from water reuse. A high-throughput functional gene array was used to study the prevalence of ARGs and VGs in aquifer biofilms (n = 27) taken from three boreholes over three months. Bacterial genera annotated as opportunistic pathogens such as Aeromonas, Burkholderia, Pseudomonas, Shewanella, and Vibrio were ubiquitous and abundant in all biofilms. Bacteria from clinically relevant genera, Campylobacter, Enterobacter, Klebsiella, Mycobacterium, Mycoplasma, and Salmonella were detected in biofilms. The mean travel time of stormwater from the injection well to P1 and P3 boreholes was 260 and 360 days respectively. The presence of ARGs and VGs in the biofilms from these boreholes suggest a high spatial movement of ARGs and VGs in the aquifer. The ARGs with the highest abundance were small multidrug resistance efflux pumps (SMR) and multidrug efflux (Mex) followed by β-lactamase C genes. β- lactamase C encoding genes were primarily detected in Enterobacteriaceae, Pseudomonadaceae, Bacillaceae, and Rhodobacteraceae families. The VGs encoding siderophores, including aerobactin (iro and iuc genes), followed by pilin, hemolysin, and type III secretion were ubiquitous. Canonical correspondence analysis suggested that Total Organic Carbon (TOC), Dissolved Organic Carbon (DOC), turbidity, and Fe concentration has a significant impact on the microbial community structure of bacteria carrying ARGs and VGs. Post abstraction treatment of groundwater may be prudent to improve water security and reduce potential health risks.202032798893
450690.9529Molecular profiling of multidrug-resistant river water isolates: insights into resistance mechanism and potential inhibitors. Polluted waters are an important reservoir for antibiotic resistance genes and multidrug-resistant bacteria. This report describes the microbial community, antibiotic resistance genes, and the genetic profile of extended spectrum β-lactamase strains isolated from rivers at, Pune, India. ESBL-producing bacteria isolated from diverse river water catchments running through Pune City were characterized for their antibiotic resistance. The microbial community and types of genes which confer antibiotic resistance were identified followed by the isolation of antibiotic-resistant bacteria on selective media and their genome analysis. Four representative isolates were sequenced using next generation sequencing for genomic analysis. They were identified as Pseudomonas aeruginosa, Escherichia coli, and two isolates were Enterobacter cloacae. The genes associated with the multidrug efflux pumps, such as tolC, macA, macB, adeL, and rosB, were detected in the isolates. As MacAB-TolC is an ABC type efflux pump responsible for conferring resistance in bacteria to several antibiotics, potential efflux pump inhibitors were identified by molecular docking. The homology model of their MacB protein with that from Escherichia coli K12 demonstrated structural changes in different motifs of MacB. Molecular docking of reported efflux pump inhibitors revealed the highest binding affinity of compound MC207-110 against MacB. It also details the potential efflux pump inhibitors that can serve as possible drug targets in drug development and discovery.202031236860
6367100.9528Comparative Drug Resistance Reversal Potential of Natural Glycosides: Potential of Synergy Niaziridin & Niazirin. BACKGROUND: Due to the limited availability of antibiotics, Gram-negative bacteria (GNB) acquire different levels of drug resistance. It raised an urgent need to identify such agents, which can reverse the phenomenon of drug resistance. OBJECTIVE: To understand the mechanism of drug resistance reversal of glycosides; niaziridin and niazirin isolated from the pods of Moringa oleifera and ouabain (control) against the clinical isolates of multidrug-resistant Escherichia coli. METHODS: The MICs were determined following the CLSI guidelines for broth micro-dilution. In-vitro combination studies were performed by broth checkerboard method followed by Time-Kill studies, the efflux pump inhibition assay, ATPase inhibitory activity, mutation prevention concentration and in-silico studies. RESULTS: The results showed that both glycosides did not possess antibacterial activity of their own, but in combination, they reduced the MIC of tetracycline up to 16 folds. Both were found to inhibit efflux pumps, but niaziridin was the best. In real time expression pattern analysis, niaziridin was also found responsible for the down expression of the two important efflux pump acrB & yojI genes alone as well as in combination. Niaziridin was also able to over express the porin forming genes (ompA & ompX). These glycosides decreased the mutation prevention concentration of tetracycline. CONCLUSION: This is the first ever report on glycosides, niazirin and niaziridin acting as drug resistance reversal agent through efflux pump inhibition and modulation of expression pattern drug resistant genes. This study may be helpful in preparing an effective antibacterial combination against the drug-resistant GNB from a widely growing Moringa oleifera.201930977451
6179110.9528Structures of Class I and Class II Transcription Complexes Reveal the Molecular Basis of RamA-Dependent Transcription Activation. Transcription activator RamA is linked to multidrug resistance of Klebsiella pneumoniae through controlling genes that encode efflux pumps (acrA) and porin-regulating antisense RNA (micF). In bacteria, σ(70) , together with activators, controls the majority of genes by recruiting RNA polymerase (RNAP) to the promoter regions. RNAP and σ(70) form a holoenzyme that recognizes -35 and -10 promoter DNA consensus sites. Many activators bind upstream from the holoenzyme and can be broadly divided into two classes. RamA acts as a class I activator on acrA and class II activator on micF, respectively. The authors present biochemical and structural data on RamA in complex with RNAP-σ(70) at the two promoters and the data reveal the molecular basis for how RamA assembles and interacts with core RNAP and activates transcription that contributes to antibiotic resistance. Further, comparing with CAP/TAP complexes reveals common and activator-specific features in activator binding and uncovers distinct roles of the two C-terminal domains of RNAP α subunit.202234761556
4689120.9527Abundant resistome determinants in rhizosphere soil of the wild plant Abutilon fruticosum. A metagenomic whole genome shotgun sequencing approach was used for rhizospheric soil micribiome of the wild plant Abutilon fruticosum in order to detect antibiotic resistance genes (ARGs) along with their antibiotic resistance mechanisms and to detect potential risk of these ARGs to human health upon transfer to clinical isolates. The study emphasized the potential risk to human health of such human pathogenic or commensal bacteria, being transferred via food chain or horizontally transferred to human clinical isolates. The top highly abundant rhizospheric soil non-redundant ARGs that are prevalent in bacterial human pathogens or colonizers (commensal) included mtrA, soxR, vanRO, golS, rbpA, kdpE, rpoB2, arr-1, efrA and ileS genes. Human pathogenic/colonizer bacteria existing in this soil rhizosphere included members of genera Mycobacterium, Vibrio, Klebsiella, Stenotrophomonas, Pseudomonas, Nocardia, Salmonella, Escherichia, Citrobacter, Serratia, Shigella, Cronobacter and Bifidobacterium. These bacteria belong to phyla Actinobacteria and Proteobacteria. The most highly abundant resistance mechanisms included antibiotic efflux pump, antibiotic target alteration, antibiotic target protection and antibiotic inactivation. antimicrobial resistance (AMR) families of the resistance mechanism of antibiotic efflux pump included resistance-nodulation-cell division (RND) antibiotic efflux pump (for mtrA, soxR and golS genes), major facilitator superfamily (MFS) antibiotic efflux pump (for soxR gene), the two-component regulatory kdpDE system (for kdpE gene) and ATP-binding cassette (ABC) antibiotic efflux pump (for efrA gene). AMR families of the resistance mechanism of antibiotic target alteration included glycopeptide resistance gene cluster (for vanRO gene), rifamycin-resistant beta-subunit of RNA polymerase (for rpoB2 gene) and antibiotic-resistant isoleucyl-tRNA synthetase (for ileS gene). AMR families of the resistance mechanism of antibiotic target protection included bacterial RNA polymerase-binding protein (for RbpA gene), while those of the resistance mechanism of antibiotic inactivation included rifampin ADP-ribosyltransferase (for arr-1 gene). Better agricultural and food transport practices are required especially for edible plant parts or those used in folkloric medicine.202337646836
6374130.9526Determining the effect of a new truncated CecropinA-Magenin2 (CE-MA) hybrid peptide on the expression of multidrug-resistant (MDR) Mycobacterium tuberculosis efflux genes. A significant issue in treating bacterial infections is multidrug resistance (MDR) microbes. Drug efflux pumps that reduce cellular drug accumulation are frequently linked to drug resistance. In this study, we set out to determine the effects of CE-MA truncated peptide derivatives against MDR Mycobacterium tuberculosis. Following the assessment of the minimum inhibitory concentrations (MICs) of these peptides against MDR Mycobacterium tuberculosis, a Real-Time PCR was used to examine the expression of six drug efflux pump genes. Next, an MTT assay was performed to test the cytotoxicity of peptides against the A549 cell line. The outcomes demonstrated that CE-MA significantly upregulated gene expression of mmr, and Rv0876c (⩾ 4-fold) than untreated bacteria. Also, under CMt2 stress, significant overexpression of Rv0876c and drrA was seen. However, the results show that upregulation in CMt2-treated bacteria in comparison CE-MA treated bacteria is significantly less for genes tap (P < 0.05), mmr (P < 0.0001), and Rv0876c (P < 0.001). Meanwhile, CMt1 only upregulated the Rv0876c gene and downregulated gene expression of tap, drrA, and mmr. It was also found that all three peptides have no significant effect (P > 0.05) on changing the expression of genes drrC and pstB. Less than 10% of the A549 cell line was susceptible to the toxicity of CMt1 and CMt2 at their MICs range. Our results emphasize the significance of investigating novel peptide-based approaches to combat MDR Mycobacterium tuberculosis and point to these peptides as prospective candidates for additional research.202540178610
1784140.9526Draft genome sequence of a multidrug-resistant emerging pathogenic isolate of Vibrio alginolyticus from the Red Sea. The marine ecosystem is a growing reservoir of antimicrobial-resistant bacteria, and thus an emerging risk to human health. In this study, we report the first draft genome sequence of multidrug-resistant Vibrio alginolyticus strain OS1T-47, isolated from an offshore site in the Red Sea. The draft genome of V. alginolyticus OS1T-47 is 5 157 150 bp in length and has DNA G + C content of 44.83%. Strain OS1T-47 possesses 22 antimicrobial resistance genes, including those associated with multidrug-resistant efflux pumps.202033294196
5747150.9525Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria. Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs) and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT)-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001) and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin) on clinical bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli). The AZT-resistance genes (ermA, ermB, ermC, mefA, and msrA) were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L). When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7-AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus strain synergistically affected by DP7-AZT showed no noteworthy morphological changes, suggesting that a molecular-level mechanism plays an important role in the synergistic action of DP7-AZT. AMP DP7 plus the antibiotic AZT or VAN is more effective, especially against highly antibiotic-resistant strains.201728356719
5134160.9525Genomic analysis and antibiotic resistance of a multidrug-resistant bacterium isolated from pharmaceutical wastewater treatment plant sludge. Pharmaceutical wastewater treatment plants (PWWTPs) serve as reservoirs for antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). In this study, a multiantibiotic-resistant strain of Acinetobacter lwoffii (named N4) was isolated from the dewatered sludge of a PWWTP. N4 exhibited high resistance to both antibiotics and metals, with minimum inhibitory concentrations (MICs) of chloramphenicol and cefazolin reaching 1024 mg·L(-1) and MICs of Cu(2+) and Zn(2+) reaching 512 mg·L(-1). Co-sensitization experiments revealed that when antibiotics are co-existing with heavy metal ions (such as TET and Cd(2+), AMP and Cu(2+)) could enhance the resistance of N4 to them. Whole-genome sequencing of N4 revealed a genome size of 0.37 Mb encoding 3359 genes. Among these, 23 ARGs were identified, including dfrA26, bl2be(CTXM), catB3, qnrB, rosB, tlrC, smeD, smeE, mexE, ceoB, oprN, acrB, adeF, ykkC, ksgA and sul2, which confer resistance through mechanisms such as efflux pumps, enzyme modification and target bypass. Additionally, the N4 genome contained 187 genes associated with human disease and 249 virulence factors, underscoring its potential pathogenicity. Overall, this study provides valuable insights into ARBs in PWWTPs and highlights the potential risks posed by multidrug-resistant strains such as N4.202539626482
5753170.9525Sensitization of Gram-Negative Bacteria to Aminoglycosides with 2-Aminoimidazole Adjuvants. In 2019, five million deaths associated with antimicrobial resistance were reported by The Centers for Disease Control and Prevention (CDC). Acinetobacter baumannii, a Gram-negative bacterial pathogen, is among the list of urgent threats. Previously, we reported 2-aminoimidazole (2-AI) adjuvants that potentiate macrolide activity against A. baumannii. In this study, we identify several of these adjuvants that sensitize A. baumannii to aminoglycoside antibiotics. Lead compounds 1 and 7 lower the tobramycin (TOB) minimum inhibitory concentration (MIC) against the TOB-resistant strain AB5075 from 128 μg/mL to 2 μg/mL at 30 μM. In addition, the lead compounds lower the TOB MIC against the TOB-susceptible strain AB19606 from 4 μg/mL to 1 μg/mL and 0.5 μg/mL, respectively, at 30 μM and 15 μM. The evolution of resistance to TOB and 1 in AB5075 revealed mutations in genes related to protein synthesis, the survival of bacteria under environmental stressors, bacteriophages, and proteins containing Ig-like domains.202337998765
481180.9524Characterization and structure prediction of partial length protein sequences of pcoA, pcoR and chrB genes from heavy metal resistant bacteria from the Klip River, South Africa. The Klip River has suffered from severe anthropogenic effects from industrial activities such as mining. Long-term exposure to heavy metal pollution has led to the development of heavy metal resistant strains of Pseudomonas sp. KR23, Lysinibacillus sp. KR25, and E. coli KR29. The objectives of this study were to characterize the genetics of copper and chromate resistance of the isolates. Copper and chromate resistance determinants were cloned and sequenced. Open reading frames (ORFs) related to the genes CopA and CopR were identified in E. coli KR29, PcoA in Lysinibacillus sp. KR25 and none related to chromate resistance were detected. The 3D-models predicted by I-TASSER disclose that the PcoA proteins consist of β-sheets, which form a part of the cupredoxin domain of the CopA copper resistance family of genes. The model for PcoR_29 revealed the presence of a helix turn helix; this forms part of a DNA binding protein, which is part of a heavy metal transcriptional regulator. The bacterial strains were cured using ethidium bromide. The genes encoding for heavy metal resistance and antibiotic resistance were found to be located on the chromosome for both Pseudomonas sp. (KR23) and E. coli (KR29). For Lysinibacillus (KR25) the heavy metal resistance determinants are suspected to be located on a mobile genetic element, which was not detected using gel electrophoresis.201525837632
6366190.9524Fluorinated Beta-diketo Phosphorus Ylides Are Novel Efflux Pump Inhibitors in Bacteria. BACKGROUND: One of the most important resistance mechanisms in bacteria is the increased expression of multidrug efflux pumps. To combat efflux-related resistance, the development of new efflux pump inhibitors is essential. MATERIALS AND METHODS: Ten phosphorus ylides were compared based on their MDR-reverting activity in multidrug efflux pump system consisting of the subunits acridine-resistance proteins A and B (AcrA and AcrB) and the multidrug efflux pump outer membrane factor TolC (TolC) of Escherichia coli K-12 AG100 strain and its AcrAB-TolC-deleted strain. Efflux inhibition was assessed by real-time fluorimetry and the inhibition of quorum sensing (QS) was also investigated. The relative gene expression of efflux QS genes was determined by real-time reverse transcriptase quantitative polymerase chain reaction. RESULTS: The most potent derivative was Ph(3)P=C(COC(2)F(5))CHO and its effect was more pronounced on the AcrAB-TolC-expressing E. coli strain, furthermore the most active compounds, Ph(3)P=C(COCF(3))OMe, Ph(3)P=C(COC(2)F(5))CHO and Ph(3)P=C(COCF(3))COMe, reduced the expression of efflux pump and QS genes. CONCLUSION: Phosphorus ylides might be valuable EPI compounds to reverse efflux related MDR in bacteria.201627815466