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Antibiotic Efflux

Inga V Leus, Jon W Weeks, Vincent Bonifay, Lauren Smith, Sophie Richardson, Helen I Zgurskaya
Antibiotic resistant Acinetobacter baumannii causes infections that are extremely difficult to treat. A significant role in these resistance profiles is attributed to multidrug efflux pumps, especially those belonging to Resistance-Nodulation-cell Division (RND) superfamily of transporters. In this study, we analyzed functions and properties of RND efflux pumps in A. baumannii ATCC 17978. This strain is susceptible to antibiotics and does not contain mutations that are commonly selected upon exposure to high concentrations of antibiotics...
April 16, 2018: Journal of Bacteriology
Xi Liu, Shu Yang, Yangqing Wang, He-Ping Zhao, Liyan Song
Landfill is important reservoirs of residual antibiotics and antibiotic resistance genes (ARGs), but the mechanism of landfill application influence on antibiotic resistance remains unclear. Although refuse decomposition plays a crucial role in landfill stabilization, its impact on the antibiotic resistance has not been well characterized. To better understand the impact, we studied the dynamics of ARGs and the bacterial community composition during refuse decomposition in a bench-scale bioreactor after long term operation (265d) based on metagenomics analysis...
April 12, 2018: Science of the Total Environment
Claire de Curraize, Catherine Neuwirth, Julien Bador, Angélique Chapuis, Lucie Amoureux, Eliane Siebor
Objectives: To characterize the structure of Salmonella genomic islands 1 (SGI1s) from two clinical Proteus mirabilis isolates: one producing an ESBL and the other a penicillinase. Methods: WGS completed by PCR and Sanger sequencing was performed to determine sequences of SGI1s from Pm2CHAMA and Pm37THOMI strains. Results: Two new variants of SGI1 named SGI1-Pm2CHAMA (53.6 kb) and SGI1-K7 (55.1 kb) were identified. The backbone of SGI1-Pm2CHAMA shared 99...
April 11, 2018: Journal of Antimicrobial Chemotherapy
Mariana Papalia, Germán Traglia, Melina Ruggiero, Marisa Almuzara, Carlos Vay, Gabriel Gutkind, Soledad María Ramírez, Marcela Radice
OBJECTIVES: The aim of this study was to characterize OXA-258 variants and other features that may contribute to the carbapenem resistant in Achromobacter ruhlandii. METHODS: Kinetic parameters for purified OXA-258a and OXA-258b were determined measuring the rate of hydrolysis of a representative group of antibiotics. Whole-genome shotgun sequencing was performed on A. ruhlandii 38 (producing OXA-258a) and A. ruhlandii 319 (producing OXA-258b) and in silico analysis of antimicrobial resistant determinants was conducted...
April 9, 2018: Journal of Global Antimicrobial Resistance
Manlu Zhu, Xiongfeng Dai
Environmental stresses often co-occur when bacteria encounter antibiotic treatment inside the human body. The cellular response to environmental stressors can alter the global gene expression pattern of bacteria. However, the relationship between the cellular stress response and antibiotic susceptibility remains poorly understood. Here we studied the effect of high salt, an important environmental stress condition inside the human body, on bacterial susceptibility to antibiotics. We found that high salt reduces the susceptibility of Escherichia coli to tetracycline and chloramphenicol, leading to a cross-protection effect...
April 25, 2018: MSphere
Abigail J Sporer, Christopher Beierschmitt, Anastasia Bendebury, Katherine E Zink, Alexa Price-Whelan, Marisa C Buzzeo, Laura M Sanchez, Lars E P Dietrich
The activities of critical metabolic and regulatory proteins can be altered by exposure to natural or synthetic redox-cycling compounds. Many bacteria, therefore, possess mechanisms to transport or transform these small molecules. The opportunistic pathogen Pseudomonas aeruginosa PA14 synthesizes phenazines, redox-active antibiotics that are toxic to other organisms but have beneficial effects for their producer. Phenazines activate the redox-sensing transcription factor SoxR and thereby induce the transcription of a small regulon, including the operon mexGHI-opmD, which encodes an efflux pump that transports phenazines, and PA14_35160 (pumA), which encodes a putative monooxygenase...
April 9, 2018: Microbiology
Yinfang Shen, Jiehao Cai, Mark R Davies, Chi Zhang, Kun Gao, Dan Qiao, Haoqin Jiang, Weilei Yao, Yuefang Li, Mei Zeng, Mingliang Chen
Streptococcus pyogenes , also known as group A Streptococcus (GAS), is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ) non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS...
2018: Frontiers in Microbiology
Leonardo N Andrade, Thiago E S Siqueira, Roberto Martinez, Ana Lucia C Darini
Bacterial resistance to antibiotics is concern in healthcare-associated infections. On the other hand, bacterial tolerance to other antimicrobials, like heavy metals, has been neglected and underestimated in hospital pathogens. Silver has long been used as an antimicrobial agent and it seems to be an important indicator of heavy metal tolerance. To explore this perspective, we searched for the presence of acquired silver resistance genes ( sil operon: silE, silS, silR, silC, silF, silB, silA , and silP ) and acquired extended-spectrum cephalosporin and carbapenem resistance genes ( bla CTX-M and bla KPC ) in Enterobacter cloacae Complex (EcC) ( n = 27) and Enterobacter aerogenes ( n = 8) isolated from inpatients at a general hospital...
2018: Frontiers in Microbiology
Vijaya Bharathi Srinivasan, Govindan Rajamohan
In this study, we present the genome sequence of Serratia marcescens SM03, recovered from a human gut in India. The final assembly consists of 26 scaffolds (4620 coding DNA sequences, 5.08 Mb, 59.6% G + C ratio) and 79 tRNA genes. Analysis identified novel genes associated with lactose utilization, virulence, P-loop GTPases involved in urease production, CFA/I fimbriae apparatus and Yersinia - type CRISPR proteins. Antibiotic susceptibility testing indicated drug tolerant phenotype and inhibition assays demonstrated involvement of extrusion in resistance...
April 5, 2018: Genomics
Reza Ghotaslou, Mina Yekani, Mohammad Yousef Memar
The resistance of Bacteroides fragilis to the most antimicrobial agents has been reported in the world. Identification of the microbial resistance mechanisms can play an important role in controlling these resistances. Currently, B. fragilis is resistant to most antibiotics. The multi-drug efflux pumps have been shown to underlie the antimicrobial resistance in B. fragilis strains. Two types of these efflux pumps including RND and MATE can be regarded as main structures responsible for antibiotic resistance...
May 2018: Microbiological Research
Zhangqi Shen, Yang Wang, Qijing Zhang, Jianzhong Shen
Campylobacter is a major foodborne pathogen and has become increasingly resistant to clinically important antimicrobials. To cope with the selection pressure from antimicrobial use in both veterinary and human medicine, Campylobacter has developed multiple mechanisms for antibiotic resistance, including modification or mutation of antimicrobial targets, modification or inactivation of antibiotics, and reduced drug accumulation by drug efflux pumps. Some of these mechanisms confer resistance to a specific class of antimicrobials, while others give rise to multidrug resistance...
April 2018: Microbiology Spectrum
Fabian Lentz, Norbert Reiling, Ana Martins, Joseph Molnár, Andreas Hilgeroth
The number of effective first-line antibiotics for the treatment of Mycobacterium tuberculosis infection is strongly limited to a few drugs. Due to emerging resistance against those drugs, second- and third-line antibiotics have been established in therapy with certain problems and also increasing mycobacterial resistance. An alternative to such novel drugs or combined therapeutic regimes which may reduce resistance development is finding enhancers of mycobacterial drug effectiveness, especially enhancers that counteract causative resistance mechanisms...
April 4, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
María Blanca Sánchez, José Luis Martínez
Cotrimoxazole is one of the antimicrobials of choice for treating Stenotrophomonas maltophilia infections. Most works on the molecular epidemiology of resistance to this drugs combination are based in the analysis of sul genes. Nevertheless, the existence of clinical cotrimoxazole resistant S. maltophilia isolates that do not harbor sul genes has been reported. To investigate potential mutations that can reduce the susceptibility of S. maltophilia to cotrimoxazole, spontaneous S. maltophilia cotrimoxazole resistant mutants isolated under different cotrimoxazole concentrations were studied...
April 2, 2018: Antimicrobial Agents and Chemotherapy
Benjamin K Chan, Paul E Turner, Samuel Kim, Hamid R Mojibian, John A Elefteriades, Deepak Narayan
Management of prosthetic vascular graft infections caused by Pseudomonas aeruginosa can be a significant challenge to clinicians. These infections often do not resolve with antibiotic therapy alone due to antibiotic resistance/tolerance by bacteria, poor ability of antibiotics to permeate/reduce biofilms and/or other factors. Bacteriophage OMKO1 binding to efflux pump proteins in P. aeruginosa was consistent with an evolutionary trade-off: wildtype bacteria were killed by phage whereas evolution of phage-resistance led to increased antibiotic sensitivity...
2018: Evolution, Medicine, and Public Health
Shimon Schuldiner
Multidrug transporters function in a coordinated mode to provide an essential first-line defense mechanism that prevents antibiotics fromreaching lethal concentrations, until a number of stable efficient adaptations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. The close interaction between the two types of transporters ensures handling of a wide range of xenobiotics and prevents rapid leak of the hydrophobic substrates back into the cell...
March 21, 2018: Research in Microbiology
Takehiko Kenzaka, Katsuji Tani
Migratory birds serve as vectors by transmitting antibiotic-resistant bacteria across large distances. Here, we isolated a multidrug-resistant Stenotrophomonas pavanii strain, BWK1, from Mareca penelope feces. Analysis of the draft genome sequence of the isolated strain indicated that BWK1 harbors a class A beta-lactamase, metallo-beta-lactamase, and several multidrug efflux pumps.
March 22, 2018: Genome Announcements
Takehiko Kenzaka, Katsuji Tani
Migratory birds are potential vehicles of antibiotic-resistant bacteria. Here, we isolated the multidrug-resistant Pseudomonas fluorescens strain BWKM6 from the feces of Mareca penelope The strain's draft genome sequence indicates that it harbors a metallo-beta-lactamase, a class C beta-lactamase, and several multidrug efflux pumps.
March 22, 2018: Genome Announcements
Carly Logan, Amber L LaCrosse, Lori A Knackstedt
Cocaine use disorder is a chronically relapsing disease without FDA-approved treatments. Using a rodent model of cocaine relapse, we and others have previously demonstrated that the beta-lactam antibiotic ceftriaxone attenuates cue- and cocaine-primed reinstatement of cocaine-seeking. Ceftriaxone restores cocaine-induced deficits in both system xc- and GLT-1 expression and function in the nucleus accumbens core (NAc). We recently demonstrated that restoration of GLT-1 expression in the NAc is necessary for ceftriaxone to attenuate reinstatement of cocaine-seeking...
March 19, 2018: Neuropharmacology
Xuan Qin, Chuan Zhou, Danielle M Zerr, Amanda Adler, Amin Addetia, Shuhua Yuan, Alexander L Greninger
Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability. Pseudomonas aeruginosa isolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains ( n = 224 from 56 CF patients, n = 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CF P...
March 2018: MSphere
Jiaoe Chen, Liping Ye, Liangmin Jin, Xuehua Xu, Peisong Xu, Xianjun Wang, Hongzhang Li
BACKGROUND: Clarithromycin (CLR) resistance has become a predominant factor for treatment failure of Helicobacter pylori eradication. Although the molecular mechanism of CLR resistance has been clearly understood in H. pylori, it is lack of evidence of other genes involved in drug resistance. Furthermore, the molecular mechanism of phenotype susceptible to CLR while genotype of 23S rRNA is mutant with A2143G is unclear. Here, we characterized the mutations of CLR-resistant and -susceptible H...
March 22, 2018: Annals of Clinical Microbiology and Antimicrobials
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