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bacterial efflux

Jack Wright, Stephen P Muench, Adrian Goldman, Alison Baker
Transport of molecules and ions across biological membranes is an essential process in all organisms. It is carried out by a range of evolutionarily conserved primary and secondary transporters. A significant portion of the primary transporters belong to the ATP-binding cassette (ABC) superfamily, which utilise the free-energy from ATP hydrolysis to shuttle many different substrates across various biological membranes, and consequently, are involved in both normal and abnormal physiology. In humans, ABC transporter-associated pathologies are perhaps best exemplified by multidrug-resistance transporters that efflux many xenobiotic compounds due to their remarkable substrate polyspecificity...
December 4, 2018: Biochemical Society Transactions
Jian Li, Kristen Kolberg, Ulrich Schlecht, Robert P St Onge, Ana Maria Aparicio, Joe Horecka, Ronald W Davis, Maureen E Hillenmeyer, Colin Jb Harvey
Multidrug resistance is highly conserved in mammalian, fungal, and bacterial cells, is characterized by resistance to several unrelated xenobiotics, and poses significant challenges to managing infections and many cancers. Eukaryotes use a highly conserved set of drug efflux transporters that confer pleiotropic drug resistance (PDR). To interrogate the regulation of this critical process, here we developed a small molecule-responsive biosensor that couples transcriptional induction of PDR genes to growth rate in the yeast Saccharomyces cerevisiae...
December 4, 2018: Journal of Biological Chemistry
Hui Lin, Stephen J Chapman, Thomas E Freitag, Carol Kyle, Junwei Ma, Yuyi Yang, Zulin Zhang
This study provided an assessment of the environmental fate of antibiotic resistance genes (ARGs) in a Scottish grassland field repeatedly treated with different organic fertilizers. The impacts of manure, biosolids and municipal food-derived compost on the relative abundances of tetracycline ARGs (tetA, tetB, tetC, tetG and tetW), sulfonamide ARGs (sul1 and sul2) and class 1 integron-integrase gene (IntI1) in soils were investigated, with inorganic fertilizer (NPK) as a comparison. The background soil with a history of low intensity farming showed a higher total relative abundance of tet ARGs over sul ARGs, with tetracycline efflux genes occurring in a higher frequency...
December 1, 2018: Ecotoxicology and Environmental Safety
Patrick T LaBreck, Gregory K Rice, Adrian C Paskey, Emad M Elassal, Regina Z Cer, Natasha N Law, Carey D Schlett, Jason W Bennett, Eugene V Millar, Michael W Ellis, Theron Hamilton, Kimberly A Bishop-Lilly, D Scott Merrell
Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTI). Some S. aureus strains harbor plasmids that carry genes that affect resistance to biocides. Among these genes, qacA encodes the QacA Multidrug Efflux Pump that imparts decreased susceptibility to chlorhexidine, a biocide used ubiquitously in healthcare facilities. Furthermore, chlorhexidine has been considered as a S. aureus decolonization strategy in community settings. We previously conducted a chlorhexidine-based SSTI prevention trial among Ft...
2018: Frontiers in Microbiology
Jiao Li, Donghong Liu, Xiaojun Tian, Shigenobu Koseki, Shiguo Chen, Xingqian Ye, Tian Ding
Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious bacterial pathogen that induces high mortality and morbidity. Due to the emergence of multiple resistance, antibiotic treatments are rapidly becoming ineffective for the related infections. Natural products, especially those derived from plants, have been proven to be effective agents with unique antibacterial properties through different mechanisms. This review interprets the resistance mechanisms of MRSA with the aim to conquer public health threat...
December 3, 2018: Critical Reviews in Food Science and Nutrition
Akinwale Ajayi David, Shang Eun Park, Keykavous Parang, Rakesh Kumar Tiwari
The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria develop resistance to antibiotics by one or more combination of resistance mechanisms namely, efflux pump activation thereby reducing bacteria intracellular antibiotic concentration, synthesizing a protein that protects target site causing poor antibiotic affinity to the binding site, or mutations in DNA and topoisomerase gene coding that alters residues in the binding sites...
November 29, 2018: Current Topics in Medicinal Chemistry
Oluwagbemiga Sewanu Soyingbe, Nkoana Ishmael Mongalo, Tshepiso Jan Makhafola
BACKGROUND: Compounds having both anticancer and antimicrobial activity have promising therapeutic potential due to their selective cytotoxicity and their potential to reduce the occurrence of bacterial and fungal infections in immune-compromised cancer patients. In our quest to find new antimicrobial agents with potent anticancer activity, the biological potential of leaves from the three medicinal plants Centella asiatica, Warburgia salutaris and Curtisia dentata as used by Zulu traditional healers for the treatment of cancer is investigated...
November 29, 2018: BMC Complementary and Alternative Medicine
Ramkumar Iyer, Samir H Moussa, Ruben Tommasi, Alita A Miller
The susceptibility of small molecules to Gram-negative bacterial efflux is typically evaluated using an antibacterial activity-based efflux ratio, which is computed as the ratio of the antibacterial activity for a wild-type strain and its isogenic efflux mutant (typically lacking genes encoding major efflux pumps). The magnitude of the ratio is often used as an efflux index. However, early in drug discovery, hits with sub-optimal physicochemical properties often lack whole cell inhibition against wild-type strains, which makes efflux ratios indeterminable...
November 29, 2018: ACS Infectious Diseases
Hans Prochnow, Verena Fetz, Sven-Kevin Hotop, Mariel García Rivera, Axel Heumann, Mark Brönstrup
Infections by Gram-negative pathogens represent a major health care issue of growing concern due to a striking lack of novel antibacterial agents over the course of the last decades. The main scientific problem behind the rational optimization of novel antibiotics is our limited understanding of small molecule translocation into, and their export from the target compartments of Gram-negative species. To address this issue, a versatile, label-free assay to determine the intracellular localization and concentration of a given compound has been developed for Escherichia coli and its efflux-impaired ΔTolC mutant...
November 28, 2018: Analytical Chemistry
Anca D Petrescu, Jessica Kain, Victoria Liere, Trace Heavener, Sharon DeMorrow
The Hypothalamic-Pituitary-Adrenal (HPA) axis has an important role in maintaining the physiological homeostasis in relation to external and internal stimuli. The HPA axis dysfunctions were extensively studied in neuroendocrine disorders such as depression and chronic fatigue syndrome but less so in hepatic cholestasis, cirrhosis or other liver diseases. The HPA axis controls many functions of the liver through neuroendocrine forward signaling pathways as well as negative feedback mechanisms, in health and disease...
2018: Frontiers in Endocrinology
Corinne E Rouquette-Loughlin, Jennifer L Reimche, Jacqueline T Balthazar, Vijaya Dhulipala, Kim M Gernert, Ellen N Kersh, Cau D Pham, Kevin Pettus, A Jeanine Abrams, David L Trees, Sancta St Cyr, William M Shafer
Recent reports suggest that mosaic-like sequences within the mtr ( m ultiple t ransferable r esistance) efflux pump locus of Neisseria gonorrhoeae , likely originating from commensal Neisseria sp. by transformation, can increase the ability of gonococci to resist structurally diverse antimicrobials. Thus, acquisition of numerous nucleotide changes within the mtrR gene encoding the transcriptional repressor (MtrR) of the mtrCDE efflux pump-encoding operon or overlapping promoter region for both along with those that cause amino acid changes in the MtrD transporter protein were recently reported to decrease gonococcal susceptibility to numerous antimicrobials, including azithromycin (Azi) (C...
November 27, 2018: MBio
Vipin Chandra Kalia, Sanjay K S Patel, Yun Chan Kang, Jung-Kul Lee
The mechanisms through which microbes communicate using signal molecules has inspired a great deal of research. Microbes use this exchange of information, known as quorum sensing (QS), to initiate and perpetuate infectious diseases in eukaryotic organisms, evading the eukaryotic defense system by multiplying and expressing their pathogenicity through QS regulation. The major issue to arise from such networks is increased bacterial resistance to antibiotics, resulting from QS-dependent mediation of the formation of biofilm, the induction of efflux pumps, and the production of antibiotics...
November 22, 2018: Biotechnology Advances
Pei Zhang, Bo Li, Jihua Wu, Shuijin Hu
Invasive plants affect soil biota through litter and rhizosphere inputs, but the direction and magnitude of these effects are variable. We conducted a meta-analysis to examine the different effects of litter and rhizosphere of invasive plants on soil communities and nutrient cycling. Our results showed that invasive plants increased bacterial biomass by 16%, detritivore abundance by 119% and microbivore abundance by 89% through litter pathway. In the rhizosphere, invasive plants reduced bacterial biomass by 12%, herbivore abundance by 55% and predator abundance by 52%, but increased AM fungal biomass by 36%...
November 20, 2018: Ecology Letters
Kelly N Chacón, Jonathan Perkins, Zachary Mathe, Katherine Alwan, Ethan N Ho, Melek N Ucisik, Kenneth M Merz, Ninian J Blackburn
Escherichia coli CusCBAF represents an important class of bacterial efflux pump exhibiting selectivity towards Cu(I) and Ag(I). The complex is comprised of three proteins: the CusA transmembrane pump, the CusB soluble adaptor protein, and the CusC outer-membrane pore, and additionally requires the periplasmic metallochaperone CusF. Here we used spectroscopic and kinetic tools to probe the mechanism of copper transfer between CusF and CusB using selenomethionine labeling of the metal-binding Met residues coupled to RFQ-XAS at the Se and Cu edges...
2018: Communications biology
Katarzyna Markowska, Anna Maria Grudniak, Barbara Milczarek, Krystyna Izabella Wolska
Listeria monocytogenes is Gram-positive bacterial pathogen, a causative agent of food poisoning and systemic disease - listeriosis. This species is still susceptible to several conventionally used antibiotics but an increase in its resistance has been reported. For this reason the search for new, alternative therapies is an urgent task. Silver nanoparticles seem to be the promising antibacterial agent. Minimal inhibitory concentration of silver nanoparticles was determined. Sublethal concentrations were used in study of nanosilver effect on cells lysis by estimation of the number of cells surviving the treatment with 0...
2018: Polish Journal of Microbiology
Tsukasa Kusakizako, Derek P Claxton, Yoshiki Tanaka, Andrés D Maturana, Teruo Kuroda, Ryuichiro Ishitani, Hassane S Mchaourab, Osamu Nureki
Multidrug and toxic compound extrusion (MATE) transporters efflux toxic compounds using a Na+ or H+ gradient across the membrane. Although the structures of MATE transporters have been reported, the cation-coupled substrate transport mechanism remains controversial. Here we report crystal structures of VcmN, a Vibrio cholerae MATE transporter driven by the H+ gradient. High-resolution structures in two distinct conformations associated with different pHs revealed that the rearrangement of the hydrogen-bonding network around the conserved Asp35 induces the bending of transmembrane helix 1, as in the case of the H+ -coupled Pyrococcus furiosus MATE transporter...
October 30, 2018: Structure
Fatma Ibrahim Sonbol, Tarek El-Said El-Banna, Ahmed Ahmed Abd El-Aziz, Engy El-Ekhnawy
AIM: Analysing the effect of step-wise exposure of Escherichia coli isolates to sub lethal concentrations of triclosan (TCS) that is widely used as antiseptic, preservative and disinfectant. METHODS AND RESULTS: The analysis included the changes in the tolerance to the biocide itself and the cross-resistance to clinically important antibiotics. The involvement of efflux mechanism was studied as well as the possible implication of modifications in cytoplasmic membrane properties including integrity, permeability, potential and depolarization in the resistance mechanisms...
November 15, 2018: Journal of Applied Microbiology
Shujian Zhang, Mukesh Jain, Laura A Fleites, Patricia Rayside, Dean Gabriel
Xylella fastidiosa infects a wide range of plant hosts and causes Pierce's disease (PD) of grapevines. The Type 1 multidrug resistance (MDR) efflux system is essential for pathogenicity and survival of bacterial pathogens in planta. X. fastidiosa, with a single MDR system, is significantly more vulnerable to inhibition by small molecule treatments than most bacterial pathogens that typically carry redundant MDR systems. A high throughput cell viability assay using a GFP-marked strain of X. fastidiosa Temecula 1 was developed to screen two Prestwick combinatorial small molecule libraries of FDA and EMA approved drugs and phytochemicals (1600 chemicals in total) for cell growth inhibition...
November 8, 2018: Phytopathology
Weichang Hu, Xiuting Hua, Qing Zhang, Jianping Wang, Qiaochu Shen, Xingtan Zhang, Kai Wang, Qingyi Yu, Yann-Rong Lin, Ray Ming, Jisen Zhang
BACKGROUND: The SWEET (Sugars Will Eventually be Exported Transporters) gene family is a recently identified group of sugar transporters that play an indispensable role in sugar efflux, phloem loading, plant-pathogen interaction, nectar secretion, and reproductive tissue development. However, little information on Saccharum SWEET is available for this crop with a complex genetic background. RESULTS: In this study, 22 SWEET genes were identified from Saccharum spontaneum Bacterial Artificial Chromosome libraries sequences...
November 7, 2018: BMC Plant Biology
Elora G Demers, Amy R Biermann, Sawyer Masonjones, Alex W Crocker, Alix Ashare, Jason E Stajich, Deborah A Hogan
Management of the limited number of antimicrobials currently available requires the identification of infections that contain drug-resistant isolates and the discovery of factors that promote the evolution of drug resistance. Here, we report a single fungal infection in which we have identified numerous subpopulations that differ in their alleles of a single gene that impacts drug resistance. The diversity at this locus was markedly greater than the reported heterogeneity of alleles conferring antibiotic resistance in bacterial infections...
November 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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