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Antibiotic Efflux

Tommaso Felicetti, Rolando Cannalire, Maria Giulia Nizi, Oriana Tabarrini, Serena Massari, Maria Letizia Barreca, Giuseppe Manfroni, Bryan D Schindler, Violetta Cecchetti, Glenn W Kaatz, Stefano Sabatini
The alarming and rapid spread of antimicrobial resistance among bacteria represents a high risk for global health. Targeting factors involved in resistance to restore the activity of failing antibiotics is a promising strategy to overcome this urgent medical need. Efflux pump inhibitors are able to increase antibiotic concentrations in bacteria, thus they can be considered true antimicrobial resistance breakers. In this work, continuing our studies on inhibitors of the Staphylococcus aureus NorA pump, we designed, synthesized and biologically evaluated novel 2-phenylquinoline derivatives starting from our hits 1 and 2...
June 6, 2018: European Journal of Medicinal Chemistry
Sravan Kumar Miryala, Sudha Ramaiah
In the present study, we have constructed an interaction network of 29 antibiotic resistant genes along with 777 interactions in E. coli O157:H7. Gene ontology analysis reveals that 94, 89 and 67 genes have roles in the cellular process, biological process and molecular function respectively. Gene complexes related to tripartite efflux pumps mdtEF-tolC and ABC family efflux pump macAB-tolC play key roles in multidrug efflux systems. It is noteworthy to mention that, 19 genes are involved in multi-efflux pumps and they play a significant role in multidrug resistance (MDR); while 18 genes are vital for fatty acid synthesis...
June 13, 2018: Genomics
Ji Lu, Min Jin, Son Hoang Nguyen, Likai Mao, Jie Li, Lachlan J M Coin, Zhiguo Yuan, Jianhua Guo
Antibiotic resistance poses a major threat to public health. Overuse and misuse of antibiotics are generally recognized as the key factors contributing to antibiotic resistance. However, whether non-antibiotic, anti-microbial (NAAM) chemicals can directly induce antibiotic resistance is unclear. We aim to investigate whether the exposure to a NAAM chemical triclosan (TCS) has an impact on inducing antibiotic resistance on Escherichia coli. Here, we report that at a concentration of 0.2 mg/L TCS induces multi-drug resistance in wild-type Escherichia coli after 30-day TCS exposure...
June 11, 2018: Environment International
Jana L Markley, Timothy A Wencewicz
Tetracyclines have been foundational antibacterial agents for more than 70 years. Renewed interest in tetracycline antibiotics is being driven by advancements in tetracycline synthesis and strategic scaffold modifications designed to overcome established clinical resistance mechanisms including efflux and ribosome protection. Emerging new resistance mechanisms, including enzymatic antibiotic inactivation, threaten recent progress on bringing these next-generation tetracyclines to the clinic. Here we review the current state of knowledge on the structure, mechanism, and inhibition of tetracycline-inactivating enzymes...
2018: Frontiers in Microbiology
Supeng Yin, Ping Chen, Bo You, Yulong Zhang, Bei Jiang, Guangtao Huang, Zichen Yang, Yu Chen, Jing Chen, Zhiqiang Yuan, Yan Zhao, Ming Li, Fuquan Hu, Yali Gong, Yizhi Peng
Pseudomonas aeruginosa is the leading cause of infection in burn patients. The increasing carbapenem resistance of P. aeruginosa has become a serious challenge to clinicians. The present study investigated the molecular typing and carbapenem resistance mechanisms of 196 P. aeruginosa isolates from the bloodstream and wound surface of patients in our burn center over a period of 6 years. By multilocus sequence typing (MLST), a total of 58 sequence types (STs) were identified. An outbreak of ST111, a type that poses a high international risk, occurred in 2014...
2018: Frontiers in Microbiology
Nicholas P Greene, Elise Kaplan, Allister Crow, Vassilis Koronakis
The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space...
2018: Frontiers in Microbiology
Corinne E Rouquette-Loughlin, Vijaya Dhulipala, Jennifer L Reimche, Erica Raterman, Afrin A Begum, Ann E Jerse, William M Shafer
The gonococcal NorM efflux pump exports substrates with a cationic moiety including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (Ts) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed herein contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly-T tract, the same transcriptional start site (TSS) was used for expression of norM Interestingly, the T-6 tract correlated with a higher level of both norM expression and gonococcal resistance to NorM substrates BE and EB...
June 11, 2018: Antimicrobial Agents and Chemotherapy
Andrew P-A Karalewitz, Samuel I Miller
Acinetobacter baumannii is a Gram negative organism that is a cause of hospital acquired multidrug resistant (MDR) infections. A. baumannii has a unique cell surface compared to many other Gram-negative pathogens in that it can live without LPS and it has a high content of cardiolipin in the outer membrane. Therefore, to better understand the cell envelope and mechanisms of A. baumannii MDR, we screened a transposon library for mutants with defective permeability barrier function, as defined as a deficiency in the ability to exclude the phosphatase chromogenic substrate, 5-Bromo-4-chloro-3-indolyl phosphate (XP)...
June 11, 2018: Antimicrobial Agents and Chemotherapy
Lemian Liu, Jian-Qiang Su, Yunyan Guo, David M Wilkinson, Zhengwen Liu, Yong-Guan Zhu, Jun Yang
Antibiotic resistance genes (ARGs) are widespread in aquatic environments, but we know little about their biogeographical distribution and occurrence at national scales. Here we analyzed the patterns of ARGs from 42 natural waterbodies (natural lakes and reservoirs) across China using high-throughput approaches. The major ARGs were multidrug genes and the main resistance mechanism was the efflux pump. Although the absolute abundance of ARGs (gene copies/L) in the south/central waterbodies was similar to the northern waterbodies, the normalized abundance of ARGs (ARGs/16S rRNA gene copy number) was higher in the south/central waterbodies than in the north (mainly because of the aminoglycoside and multidrug resistance genes)...
August 2018: Environment International
Abigail L Reens, Amy L Crooks, Chih-Chia Su, Toni A Nagy, David L Reens, Jessica D Podoll, Madeline E Edwards, Edward W Yu, Corrella S Detweiler
Bacterial efflux pumps transport small molecules from the cytoplasm or periplasm outside the cell. Efflux pump activity is typically increased in multi-drug resistant (MDR) pathogens; chemicals that inhibit efflux pumps may have potential for antibiotic development. Using an in-cell screen, we identified three efflux pump modulators (EPMs) from a drug diversity library. The screening platform uses macrophages infected with the human Gram-negative pathogen Salmonella enterica (Salmonella) to identify small molecules that prevent bacterial replication or survival within the host environment...
June 7, 2018: PLoS Pathogens
Deepti P Karumathil, Meera Surendran Nair, James Gaffney, Anup Kollanoor-Johny, Kumar Venkitanarayanan
Multi-drug resistant (MDR) Acinetobacter baumannii is a major nosocomial pathogen causing a wide range of clinical conditions with significant mortality rates. A. baumannii strains are equipped with a multitude of antibiotic resistance mechanisms, rendering them resistant to most of the currently available antibiotics. Thus, there is a critical need to explore novel strategies for controlling antibiotic resistance in A. baumannii . This study investigated the efficacy of two food-grade, plant-derived antimicrobials (PDAs), namely trans -cinnamaldehyde (TC) and eugenol (EG) in decreasing A...
2018: Frontiers in Microbiology
Cátia Pacífico, Pedro Fernandes, Carla C C R de Carvalho
Mycobacterium vaccae , a bacterium found in soil, has been receiving attention as adjuvant to antituberculosis treatment, vaccines and immunotherapies and even as antidepressant. This bacterium is also able to degrade several pollutants, including aromatic compounds. The increasing presence of organic solvents in the environment may lead to M. vaccae adapted populations. A possible relationship between solvent tolerance and decreased susceptibility to other types of chemicals, including antibiotics, may pose a problem during opportunistic infections...
2018: Frontiers in Microbiology
Luisa Sandner-Miranda, Pablo Vinuesa, Alejandro Cravioto, Rosario Morales-Espinosa
Serratia marcescens , a member of the Enterobacteriaceae family, was long thought to be a non-pathogenic bacterium prevalent in environmental habitats. Together with other members of this genus, it has emerged in recent years as an opportunistic nosocomial pathogen causing various types of infections. One important feature of pathogens belonging to this genus is their intrinsic and acquired resistance to a variety of antibiotic families, including β-lactam, aminoglycosides, quinolones and polypeptide antibiotics...
2018: Frontiers in Microbiology
Günter Kampf
Benzalkonium chloride (BAC) is a commonly used active agent in healthcare, e.g. in surface disinfectants, disinfectant cleaners or sometimes also in skin antiseptics. Aim of the review was to evaluate the potential of bacteria to adapt to low level BAC exposure. A maximum 4-fold MIC increase was found in most of the 57 evaluated bacterial species. A strong adaptive, mostly stable, MIC change was described in strains or isolates of Pantoea spp, Enterobacter spp., S. saprophyticus or E. coli (up to 500-fold, 300-fold, 200-fold or 100-fold, respectively)...
May 31, 2018: Journal of Hospital Infection
Xu Chen, Yanan Liu, Ange Lin, Na Huang, Liquan Long, Ye Gang, Jie Liu
Efflux pump system-mediated bacterial multidrug resistance is one of the main causes of antibiotic failure. Therefore, it is necessary to develop a novel nanocarrier that could effectively inhibit drug-resistant bacteria by increasing the intake and retention time of antibiotics. Herein, we constructed a pH-responsive nanocarrier (MSN@FA@CaP@FA) with double folic acid (FA) and calcium phosphate (CaP) covered on the surface of mesoporous silica (MSN) by electrostatic attraction and biomineralization, respectively...
May 31, 2018: Biomaterials Science
Manlu Zhu, Xiongfeng Dai
No abstract text is available yet for this article.
June 27, 2018: MSphere
Manju Suresh, N Nithya, P R Jayasree, K P Vimal, P R Manish Kumar
The present study deals with membrane-bound efflux pumps, MexAB-OprM and MexXY and their respective regulatory genes mexR, nalC, nalD and mexZ in multidrug resistant (MDR) Pseudomonas aeruginosa. Following antibiotic sensitivity testing and detection of various beta-lactamases, hyperexpression of efflux pump genes, mexB and mexY in the isolates was investigated using semi-quantitative and real-time reverse transcription-PCR. Amplicons from regulatory genes were sequenced and subjected to mutational and phylogenetic analysis...
May 30, 2018: World Journal of Microbiology & Biotechnology
Di Wang, Kunpeng Xie, Dan Zou, Meizhu Meng, Mingjie Xie
Bacterial multidrug resistance efflux systems serve an important role in antimicrobial resistance. Thus, identifying novel and effective efflux pump inhibitors that are safe with no adverse side effects is urgently required. Silybin is a flavonolignan component of the extract from the milk thistle seed. To order to investigate the mechanism by which silybin inhibits the efflux system of methicillin‑resistant Staphylococcus aureus (MRSA), antimicrobial susceptibility testing and the double‑plate method were used to evaluate the effect of silybin on MRSA41577...
May 16, 2018: Molecular Medicine Reports
Hongna Li, Binxu Li, Zhiguo Zhang, Yunlong Tian, Jing Ye, Xiwu Lv, Changxiong Zhu
The performance of the electrokinetic remediation process on the removal of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) was evaluated with different influencing factors. With chlortetracycline (CTC), oxytetracycline (OTC), and tetracycline (TC) as template chemicals, the removal of both ARB and ARGs was enhanced with the increase of voltage gradient (0.4-1.2 V cm-1 ) and prolonged reaction time (3-14 d). The greatest removal (26.01-31.48% for ARB, 37.93-83.10% for ARGs) was obtained applying a voltage of 1...
May 25, 2018: Ecotoxicology and Environmental Safety
Martijn Zwama, Akihito Yamaguchi
The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR) in Gram-negative pathogenic bacteria. AcrB is the most thoroughly studied RND transporter and has functioned as a model for our understanding of efflux-mediated MDR. This multidrug-exporter can recognize and transport a wide range of structurally unrelated compounds (including antibiotics, dyes, bile salts and detergents), while it shows a strict inhibitor specificity...
May 25, 2018: Research in Microbiology
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