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Antibiotic Efflux

Pierre Dehoux, Jean Christophe Marvaud, Amr Abouelleil, Ashlee M Earl, Thierry Lambert, Catherine Dauga
BACKGROUND: Clostridium bolteae and Clostridium clostridioforme, previously included in the complex C. clostridioforme in the group Clostridium XIVa, remain difficult to distinguish by phenotypic methods. These bacteria, prevailing in the human intestinal microbiota, are opportunistic pathogens with various drug susceptibility patterns. In order to better characterize the two species and to obtain information on their antibiotic resistance genes, we analyzed the genomes of six strains of C...
October 21, 2016: BMC Genomics
Narges Abdali, Jerry Matthew Parks, Keith Haynes, Julie L Chaney, Adam T Green, David Wolloscheck, John K Walker, Valentin V Rybenkov, Jerome Yves Baudry, Jeremy C Smith, Helen I Zgurskaya
Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for development of effective EPIs, especially in light of constantly emerging resistance. Here, we describe EPIs that interact with periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel...
October 21, 2016: ACS Infectious Diseases
Çiğdem Yılmaz, Gülay Özcengiz
The discovery of penicillin followed by streptomycin, tetracycline, cephalosporins and other natural, semi-synthetic and synthetic antimicrobials completely revolutionized medicine by reducing human morbidity and mortality from most of the common infections. However, shortly after they were introduced to clinical practice, the development of resistance was emerged. The decreasing interest from antibiotic industry in spite of rapid global emergence of antibiotic resistance is a tough dilemma from the pointview of public health...
October 17, 2016: Biochemical Pharmacology
Sandrine Alibert, Joannah N'Gompazza Diarra, Jessica Hernandez, Aurélien Stutzmann, Marwa Fouad, Gérard Boyer, Jean-Marie Pagès
Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed...
October 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
Adrian Low, Charmaine Ng, Jianzhong He
Urban watersheds from point sources are potential reservoirs of antibiotic resistance genes (ARGs). However, few studies have investigated urban watersheds of non-point sources. To understand the type of ARGs and bacteria that might carry such genes, we investigated two non-point source urban watersheds with different land-use profiles. Antibiotic resistance levels of two watersheds (R1, R3) were examined using heterotrophic plate counts (HPC) as a culturing method to obtain counts of bacteria resistant to seven antibiotics belonging to different classes (erythromycin, kanamycin, lincomycin, norfloxacin, sulfanilamide, tetracycline and trimethoprim)...
September 20, 2016: Water Research
Wanida Phetsang, Ruby Pelingon, Mark S Butler, Sanjaya Kc, Miranda E Pitt, Geraldine Kaeslin, Matthew A Cooper, Mark A T Blaskovich
Reduced susceptibility to antimicrobials in Gram-negative bacteria may result from multiple resistance mechanisms, including increased efflux pump activity or reduced porin protein expression. Up-regulation of the efflux pump system is closely associated with multidrug resistance (MDR). To help investigate the role of efflux pumps on compound accumulation, a fluorescence-based assay was developed using fluorescent derivatives of trimethoprim (TMP), a broad-spectrum synthetic antibiotic that inhibits an intracellular target, dihydrofolate reductase (DHFR)...
October 14, 2016: ACS Infectious Diseases
Zhe-Xian Tian, Xue-Xian Yi, Anna Cho, Fergal O'Gara, Yi-Ping Wang
Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified upstream of the mexA promoter in all genome-sequenced P. aeruginosa strains. CpxR is required to enhance mexAB-oprM expression and drug resistance, in the absence of repressor MexR, in P...
October 2016: PLoS Pathogens
Angeliki Mavroidi, Maria Katsiari, Eleftheria Palla, Sofia Likousi, Zoi Roussou, Charikleia Nikolaou, Evangelia D Platsouka
A rapid increase was observed in the incidence of extensively drug-resistant Acinetobacter baumannii (XDR Aba) isolates in a Greek hospital during 2014. To investigate the causes of this rise, the antimicrobial resistance profiles of all carbapenem-resistant (CARB-R) Aba isolates recovered during 2014-2015 were determined. Selected XDR Aba isolates (n = 13) were characterized by molecular methods. XDR Aba (48 isolates) represented 21.4% of the 224 CARB-R Aba recovered during the study period. The 13 selected XDR Aba isolates were positive for the blaOXA-23, the intrinsic blaOXA-51, and the adeB gene of the AdeABC efflux pump, and all belonged to the 3LST ST101, corresponding to the international clone II...
October 11, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
Yanmei Sun, Yue-Xiao Shen, Peng Liang, Jizhong Zhou, Yunfeng Yang, Xia Huang
Wastewater treatment plants are thought to be potential reservoirs of antibiotic resistance genes. In this study, GeoChip was used for analyzing multiple antibiotic resistance genes, including four multidrug efflux system gene groups and three β-lactamase genes in ten large-scale membrane bioreactors (MBRs) for municipal wastewater treatment. Results revealed that the diversity of antibiotic genes varied a lot among MBRs, but about 40% common antibiotic resistance genes were existent. The average signal intensity of each antibiotic resistance group was similar among MBRs, nevertheless the total abundance of each group varied remarkably and the dominant resistance gene groups were different in individual MBR...
September 30, 2016: Bioresource Technology
Yasemin Cag, Hulya Caskurlu, Yanyan Fan, Bin Cao, Haluk Vahaboglu
By definition, the terms sepsis and septic shock refer to a potentially fatal infectious state in which the early administration of an effective antibiotic is the most significant determinant of the outcome. Because of the global spread of resistant bacteria, the efficacy of antibiotics has been severely compromised. S. pneumonia, Escherichia coli (E. coli), Klebsiella, Acinetobacter, and Pseudomonas are the predominant pathogens of sepsis and septic shock. It is common for E. coli, Klebsiella, Acinetobacter and Pseudomonas to be resistant to multiple drugs...
September 2016: Annals of Translational Medicine
Max R Schroeder, David S Stephens
Streptococcus pneumoniae is a common commensal and an opportunistic pathogen. Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Macrolides are bacteriostatic antibiotics and inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread use of macrolides is associated with increased macrolide resistance in S. pneumoniae, and the treatment of pneumococcal infections with macrolides may be associated with clinical failures. In S...
2016: Frontiers in Cellular and Infection Microbiology
Manuel Alcalde-Rico, Sara Hernando-Amado, Paula Blanco, José L Martínez
Multidrug efflux pumps can be involved in bacterial resistance to antibiotics at different levels. Some efflux pumps are constitutively expressed at low levels and contribute to intrinsic resistance. In addition, their overexpression may allow higher levels of resistance. This overexpression can be transient, in the presence of an effector (phenotypic resistance), or constitutive when mutants in the regulatory elements of the expression of efflux pumps are selected (acquired resistance). Efflux pumps are present in all cells, from human to bacteria and are highly conserved, which indicates that they are ancient elements in the evolution of different organisms...
2016: Frontiers in Microbiology
Nopphasul Sirijant, Rasana W Sermswan, Surasakdi Wongratanacheewin
Burkholderia pseudomallei, the causative agent of melioidosis, has been found to increase its resistance to antibiotics when growing as a biofilm. The resistances are related to several mechanisms. One of the possible mechanisms is the efflux pump. Using bioinformatics analysis, it was found that BPSL1661, BPSL1664 and BPSL1665 were orthologous genes of the efflux transporter encoding genes for biofilm related antibiotic resistance PA1874-PA1877 genes in Pseudomonas aeruginosa strain PAO1. Expressions of selected encoding genes for the efflux transporter system during biofilm formation were investigated...
September 30, 2016: Journal of Medical Microbiology
Ganesh Krishnamoorthy, David Wolloscheck, Jon W Weeks, Cameron Croft, Valentin V Rybenkov, Helen I Zgurskaya
In Gram-negative bacteria, a synergistic relationship between slow passive uptake of antibiotics across the outer membrane and active efflux transporters creates a permeability barrier, which efficiently reduces effective concentrations of antibiotics in cells and hence, their activities. To analyze the relative contributions of the active efflux and the passive barrier in activities of antibiotics, we constructed Escherichia coli strains with controllable permeability of the outer membrane. The strains express a large pore that does not discriminate compounds based on their hydrophilicity and sensitizes cells to a variety of antibacterial agents...
October 3, 2016: Antimicrobial Agents and Chemotherapy
Paula Blanco, Sara Hernando-Amado, Jose Antonio Reales-Calderon, Fernando Corona, Felipe Lira, Manuel Alcalde-Rico, Alejandra Bernardini, Maria Blanca Sanchez, Jose Luis Martinez
Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy...
February 16, 2016: Microorganisms
Corina G Heidrich, Sanya Mitova, Andreas Schedlbauer, Sean R Connell, Paola Fucini, Judith N Steenbergen, Christian Berens
Omadacycline is an aminomethylcycline antibiotic with potent activity against many Gram-positive and Gram-negative pathogens, including strains carrying the major efflux and ribosome protection resistance determinants. This makes it a promising candidate for therapy of severe infectious diseases. Omadacycline inhibits bacterial protein biosynthesis and competes with tetracycline for binding to the ribosome. Its interactions with the 70S ribosome were, therefore, analyzed in great detail and compared with tigecycline and tetracycline...
2016: Antibiotics
Meixia Li, Chao Cai, Juan Chen, Changwei Cheng, Guofu Cheng, Xueying Hu, Cuiping Liu
Streptococcus gallolyticus subsp. pasteurianus is an under-recognized pathogen and zoonotic agent causing opportunistic infections in humans. Despite increasing recognition of this subspecies as a cause for human infectious diseases, limited information is known about its antibiotic resistance mechanism. In this study, we aim to identify the molecular mechanism underlying the high macrolide resistance of six S. gallolyticus subsp. pasteurianus isolates from dead ducklings collected in several natural outbreaks in China during 2010-2013...
2016: International Journal of Molecular Sciences
Debarati Choudhury, Deepjyoti Paul, Anindya Sundar Ghosh, Anupam Das Talukdar, Manabendra Dutta Choudhury, Anand Prakash Maurya, Debadatta Dhar Chanda, Atanu Chakravarty, Amitabha Bhattacharjee
The therapeutic option of a carbapenem antibiotic is compromised in Pseudomonas aeruginosa owing both to acquired and intrinsic resistance mechanisms. In recent years, New Delhi metallo-β-lactamase has been the focus as a predominant carbapenem resistance determinant. However, it is unclear which of the mechanisms might be adopted by a P. aeruginosa strain possessing both blaNDM-1 and an overexpressed MexAB-OprM system during carbapenem therapy. This study investigated the interplay of both mechanisms in clinical isolates of P...
September 15, 2016: Journal of Global Antimicrobial Resistance
Cláudia Gomes, Sandra Martínez-Puchol, Lidia Ruiz-Roldán, Maria J Pons, Juana Del Valle Mendoza, Joaquim Ruiz
The objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-β-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37...
September 26, 2016: Scientific Reports
Hong Yao, Zhangqi Shen, Yang Wang, Fengru Deng, Dejun Liu, Gaowa Naren, Lei Dai, Chih-Chia Su, Bing Wang, Shaolin Wang, Congming Wu, Edward W Yu, Qijing Zhang, Jianzhong Shen
UNLABELLED: Bacterial antibiotic efflux pumps are key players in antibiotic resistance. Although their role in conferring multidrug resistance is well documented, the emergence of "super" efflux pump variants that enhance bacterial resistance to multiple drugs has not been reported. Here, we describe the emergence of a resistance-enhancing variant (named RE-CmeABC) of the predominant efflux pump CmeABC in Campylobacter, a major zoonotic pathogen whose resistance to antibiotics is considered a serious antibiotic resistance threat in the United States...
2016: MBio
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