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Antibiotic Efflux

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https://www.readbyqxmd.com/read/28625995/novel-antibiotic-resistance-determinants-from-agricultural-soil-exposed-to-antibiotics-widely-used-in-human-medicine-and-animal-farming
#1
Calvin Ho-Fung Lau, Kalene van Engelen, Stephen Gordon, Justin Renaud, Edward Topp
Antibiotic resistance has emerged globally as one of the biggest threats to human and animal health. Although the excessive use of antibiotics is recognized for accelerating the selection for resistance, there is a growing body of evidence suggesting that natural environments are "hotspots" for the development of both ancient and contemporary resistance mechanisms. Given that pharmaceuticals can be entrained onto agricultural land through anthropogenic activities, this could be a potential driver for the emergence and dissemination of resistance in soil bacteria...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28621579/optimization-of-antimicrobial-photodynamic-therapy-in-biofilms-by-inhibiting-efflux-pump
#2
Tatiana Maria Starck Fogaça de Aguiar Coletti, Laura Marise de Freitas, Ana Marisa Fusco Almeida, Carla Raquel Fontana
BACKGROUND: One of the main mechanisms of microbial resistance is given by efflux pumps, which reduce the effectiveness of antimicrobials by decreasing their intracellular concentration. OBJECTIVE AND METHODS: Considering that efflux pump inhibitors are promising adjuvant molecules for antibiotics in infections, in this study, using XTT test and colony forming unit (CFU) counting, we evaluated the association between the pump inhibitor verapamil (VP) and the antimicrobial photodynamic therapy (aPDT) mediated by methylene blue (MB) in biofilms of Escherichia coli and Staphylococcus aureus to optimize the bacterial reduction...
June 15, 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/28618136/amphiphilic-cargo-loaded-nanocarrier-enhances-antibiotic-uptake-and-perturbs-efflux-effective-synergy-for-mitigation-of-methicillin-resistant-staphylococcus-aureus
#3
Durairaj Thiyagarajan, Gopal Das, Ramesh Aiyagari
A pyridinium amphiphile-loaded Poly(lactic-co-glycolic acid) (PLGA) nanocarrier (C1-PNC) was developed as an adjuvant in order to break the resistance and restore susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) cells to therapeutic antibiotics. Notably, against a clinical MRSA strain, C1-PNC could render 8 × and 6 × reduction of the minimum biofilm eradication concentration (MBEC90) of gentamicin and ciprofloxacin, respectively. Mechanistic studies on MRSA planktonic cells revealed that in case of gentamicin, C1-PNC promoted enhanced cellular uptake of the antibiotic, while the propensity of C1-PNC to inhibit efflux pump activity could be leveraged to enhance cellular accumulation of ciprofloxacin leading to effective killing of MRSA cells...
June 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28614259/global-regulator-soxr-is-a-negative-regulator-of-efflux-pump-gene-expression-and-affects-antibiotic-resistance-and-fitness-in-acinetobacter-baumannii
#4
Henan Li, Qi Wang, Ruobing Wang, Yawei Zhang, Xiaojuan Wang, Hui Wang
SoxR is a global regulator contributing to multidrug resistance in Enterobacteriaceae. However, the contribution of SoxR to antibiotic resistance and fitness in Acinetobacter baumannii has not yet been studied. Comparisons of molecular characteristics were performed between 32 multidrug-resistant A. baumannii isolates and 11 susceptible isolates. A soxR overexpression mutant was constructed, and its resistance phenotype was analyzed. The impact of SoxR on efflux pump gene expression was measured at the transcription level...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28605582/assessing-antibiotic-permeability-of-gram-negative-bacteria-via-nanofluidics
#5
SoonGweon Hong, Tobias J Moritz, Christopher M Rath, Pramila Tamrakar, Philip Lee, Thomas Krucker, Luke P Lee
While antibiotic resistance is increasing rapidly, drug discovery has proven to be extremely difficult. Antibiotic resistance transforms some bacterial infections into deadly medical conditions. A significant challenge in antibiotic discovery is designing potent molecules that enter Gram-negative bacteria and also avoid active efflux mechanisms. Critical analysis in rational drug design has been hindered by the lack of effective analytical tools to analyze the bacterial membrane permeability of small molecules...
June 16, 2017: ACS Nano
https://www.readbyqxmd.com/read/28596758/a-functional-metagenomic-analysis-of-tetracycline-resistance-in-cheese-bacteria
#6
Ana B Flórez, Lucía Vázquez, Baltasar Mayo
Metagenomic techniques have been successfully used to monitor antibiotic resistance genes in environmental, animal and human ecosystems. However, despite the claim that the food chain plays a key role in the spread of antibiotic resistance, metagenomic analysis has scarcely been used to investigate food systems. The present work reports a functional metagenomic analysis of the prevalence and evolution of tetracycline resistance determinants in a raw-milk, blue-veined cheese during manufacturing and ripening...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28594170/pharmaceutical-approaches-to-target-antibiotic-resistance-mechanisms
#7
Domenico Schillaci, Virginia Spanò, Barbara Parrino, Anna Carbone, Alessandra Montalbano, Paola Barraja, Patrizia Diana, Girolamo Cirrincione, Stella Cascioferro
There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections...
June 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28584156/the-role-of-axyz-transcriptional-regulator-in-the-overproduction-of-axyxy-oprz-multidrug-efflux-system-in-achromobacter-spp-mutants-selected-by-tobramycin
#8
Julien Bador, Catherine Neuwirth, Nadège Grangier, Marie Muniz, Leslie Germé, Jérémy Bonnet, Vignesh-Guru Pillay, Catherine Llanes, Claire de Curraize, Lucie Amoureux
AxyXY-OprZ is an RND-type efflux system that confers innate aminoglycoside resistance to Achromobacter spp. We investigated here about a putative TetR family transcriptional regulator encoded by the axyZ gene located upstream of axyXY-oprZ In-frame axyZ gene deletion assay led to increased MICs of antibiotic substrates of the efflux system: aminoglycosides, cefepime, fluoroquinolones, tetracyclines and erythromycin, indicating that the product of axyZ negatively regulates expression of axyXY-oprZ Moreover we identified an amino-acid substitution at position 29 of AxyZ (V29G) in a clinical Achromobacter strain that occurred during the course of chronic respiratory tract colonization in a cystic fibrosis (CF) patient...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28584154/pa3225-is-a-transcriptional-repressor-of-antibiotic-resistance-mechanisms-in-pseudomonas-aeruginosa
#9
Clayton W Hall, Li Zhang, Thien-Fah Mah
The tssABC1 locus is part of the Hcp secretion island (HSI) -I type VI secretion system (T6SS) in Pseudomonas aeruginosa Previous work has implicated the tssC1 gene in P. aeruginosa biofilm-specific antibiotic resistance, and tssC1 is preferentially expressed in biofilms compared to planktonic cells. Using a DNA-dependent protein pulldown approach, we discovered PA3225, an uncharacterised LysR-type transcriptional regulator that specifically bound to the tssABC1 upstream regulatory region. Deletion of PA3225 led to a two-fold decrease in tssA1 expression in planktonic cells compared to wild-type, and tssA1 expression was slightly reduced in ΔPA3225 biofilms compared to wild-type biofilms...
June 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28578196/organic-compounds-stimulate-horizontal-transfer-of-antibiotic-resistance-genes-in-mixed-wastewater-treatment-systems
#10
Ya-Nan Jiao, Hong Chen, Rui-Xia Gao, Yong-Guan Zhu, Christopher Rensing
Domestic wastewater treatment plants as a reservoir of antibiotic resistance genes (ARGs) have received much attention, but the effect of dyes on the propagation of ARGs has rarely been investigated. In this study, we investigated the differences in distributions of ARGs and microbial communities using high-throughput qPCR and 16S rRNA gene sequencing, respectively, between mixed (dyeing and domestic) wastewater and domestic sewage. The relative abundance of ARGs in inflows of mixed wastewater (IW2 and IW3) was higher than that of domestic wastewater (IW1)...
May 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/28560883/a-deletion-mutation-in-nfxb-of-in-vitro-induced-moxifloxacin-resistant-pseudomonas-aeruginosa-confers-multidrug-resistance
#11
Van Chi Thai, Hoang Vy Pham, Duc Nhat Minh Nguyen, Peter Lambert, Thi Thu Hoai Nguyen
The modulation of efflux pump functions under fluoroquinolone (FQ) exposure is of great concern as it could result in occurrence of multidrug-resistant (MDR) bacterial strains. In this study, MDR mechanism in Pseudomonas aeruginosa induced via moxifloxacin (MOX) pressure was investigated. After serial MOX [concentration of 0.5 × the minimum inhibitory concentration (MIC)] exposure, the fully susceptible P. aeruginosa ATCC 9027 strain has increased its MIC not only toward MOX (1→128 mg/L) but also to other antibiotics...
May 31, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/28549490/whole-genome-analysis-reveals-new-insights-into-macrolide-resistance-in-mycoplasma-pneumoniae
#12
Shao Li Li, Hong Mei Sun, Bao Li Zhu, Fei Liu, Han Qing Zhao
OBJECTIVE: Mutations in 23S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae (M. pneumoniae). However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. METHODS: The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina HiSeq2000 platform...
May 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28533232/potentiation-of-antibiotic-activity-by-a-novel-cationic-peptide-potency-and-spectrum-of-activity-of-spr741
#13
David Corbett, Andrew Wise, Tara Langley, Kirsty Skinner, Emily Trimby, Stephen Birchall, Alain Dorali, Stephanie Sandiford, Jennifer Williams, Peter Warn, Martti Vaara, Troy Lister
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii Of 35 antibiotics tested, the MICs of eight were reduced 32- to 8,000-fold against E...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28533185/the-small-molecule-iitr08027-restores-the-antibacterial-activity-of-fluoroquinolones-against-multidrug-resistant-acinetobacter-baumannii-by-efflux-inhibition
#14
Tapas Bhattacharyya, Atin Sharma, Jawed Akhter, Ranjana Pathania
Efflux pumps are one of the major determinants of multiple drug resistance. In this study, AbeM, a multidrug efflux pump in Acinetobacter baumannii, was cloned into a multicopy plasmid (pUC18) and was transformed into an efflux-deficient mutant of Escherichia coli (KAM32). The elevated resistance profile of the recombinant E. coli for ciprofloxacin was utilised to screen a small-molecule library of 8000 molecules to identify IITR08027, a small molecule that is not inhibitory on its own but that could potentiate the activity of ciprofloxacin...
May 19, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28530279/bifunctional-antimicrobial-conjugates-and-hybrid-antimicrobials
#15
REVIEW
P Klahn, M Brönstrup
Covering: up to the end of 2016Novel antimicrobial drugs are continuously needed to counteract bacterial resistance development. An innovative molecular design strategy for novel antibiotic drugs is based on the hybridization of an antibiotic with a second functional entity. Such conjugates can be grouped into two major categories. In the first category (antimicrobial hybrids), both functional elements of the hybrid exert antimicrobial activity. Due to the dual targeting, resistance development can be significantly impaired, the pharmacokinetic properties can be superior compared to combination therapies with the single antibiotics, and the antibacterial potency is often enhanced in a synergistic manner...
May 22, 2017: Natural Product Reports
https://www.readbyqxmd.com/read/28529506/roles-of-regulatory-rnas-for-antibiotic-resistance-in-bacteria-and-their-potential-value-as-novel-drug-targets
#16
REVIEW
Petra Dersch, Muna A Khan, Sabrina Mühlen, Boris Görke
The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28528649/metal-resistance-and-its-association-with-antibiotic-resistance
#17
Chandan Pal, Karishma Asiani, Sankalp Arya, Christopher Rensing, Dov J Stekel, D G Joakim Larsson, Jon L Hobman
Antibiotic resistance is recognised as a major global threat to public health by the World Health Organization. Currently, several hundred thousand deaths yearly can be attributed to infections with antibiotic-resistant bacteria. The major driver for the development of antibiotic resistance is considered to be the use, misuse and overuse of antibiotics in humans and animals. Nonantibiotic compounds, such as antibacterial biocides and metals, may also contribute to the promotion of antibiotic resistance through co-selection...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28528648/copper-and-antibiotics-discovery-modes-of-action-and-opportunities-for-medicinal-applications
#18
Alex G Dalecki, Cameron L Crawford, Frank Wolschendorf
Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28516210/antibiotic-resistance-genes-in-surface-water-of-eutrophic-urban-lakes-are-related-to-heavy-metals-antibiotics-lake-morphology-and-anthropic-impact
#19
Yuyi Yang, Chen Xu, Xinhua Cao, Hui Lin, Jun Wang
Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86...
May 17, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28516003/mode-of-action-of-the-2-phenylquinoline-efflux-inhibitor-pqq4r-against-escherichia-coli
#20
Diana Machado, Laura Fernandes, Sofia S Costa, Rolando Cannalire, Giuseppe Manfroni, Oriana Tabarrini, Isabel Couto, Stefano Sabatini, Miguel Viveiros
Efflux pump inhibitors are of great interest since their use as adjuvants of bacterial chemotherapy can increase the intracellular concentrations of the antibiotics and assist in the battle against the rising of antibiotic-resistant bacteria. In this work, we have described the mode of action of the 2-phenylquinoline efflux inhibitor (4-(2-(piperazin-1-yl)ethoxy)-2-(4-propoxyphenyl) quinolone - PQQ4R), against Escherichia coli, by studding its efflux inhibitory ability, its synergistic activity in combination with antibiotics, and compared its effects with the inhibitors phenyl-arginine-β-naphthylamide (PAβN) and chlorpromazine (CPZ)...
2017: PeerJ
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