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bacterial efflux

Praveen Rishi, Shania Vij, Indresh Kumar Maurya, Ujjwal Jit Kaur, Sanjay Bharati, Rupinder Tewari
Fast emerging antibiotic resistance in pathogens requires special attention for strengthening the reservoir of antimicrobial compounds. In view of this, several peptides with known antimicrobial activities have been reported to enhance the efficacy of antibiotics against multidrug resistant (MDR) pathogens. In the present study, potential of peptides having distinct mechanism of action, if any, was evaluated to improve the efficacy of conventional antibiotics against methicillin-resistant S. aureus (MRSA). After primary screening of six peptides, two peptides namely T3 and T4 showing very high minimum inhibitory concentrations (MICs) were selected to assess their role in altering the MICs of antibiotics to which the pathogen was resistant...
August 14, 2018: Microbial Pathogenesis
Antal Martinecz, Pia Abel Zur Wiesch
Treatment of infectious diseases is often long and requires patients to take drugs even after they have seemingly recovered. This is because of a phenomenon called persistence, which allows small fractions of the bacterial population to survive treatment despite being genetically susceptible. The surviving subpopulation is often below detection limit and therefore is empirically inaccessible but can cause treatment failure when treatment is terminated prematurely. Mathematical models could aid in predicting bacterial survival and thereby determine sufficient treatment length...
August 9, 2018: Pathogens and Disease
Yuxin Zhang, Wenjuan Ma, Ying Zhu, Sirong Shi, Qian-Shun Li, Chenchen Mao, Dan Zhao, Yuxi Zhan, Jiye Shi, Wei Li, Lihua Wang, Chunhai Fan, Yun-Feng Lin
One of the biggest obstacles for the use of antisense oligonucleotides as antibacterial therapeutics is their limited uptake by bacterial cells without a suitable carrier, especially in multi-drug resistant bacteria with a drug efflux mechanism. Existing vectors, such as cell-penetrating peptides, are inefficient and non-targeting, and accordingly are not ideal carriers. A non-cytotoxic tetrahedral DNA nanostructure (TDN) with a controllable conformation has been developed as a delivery vehicle for antisense oligonucleotides...
August 8, 2018: Nano Letters
Crista B Wadsworth, Brian J Arnold, Mohamad R Abdul Sater, Yonatan H Grad
Mosaic interspecifically acquired alleles of the multiple transferable resistance ( mtr ) efflux pump operon correlate with increased resistance to azithromycin in Neisseria gonorrhoeae in epidemiological studies. However, whether and how these alleles cause resistance is unclear. Here, we use population genomics, transformations, and transcriptional analyses to dissect the relationship between variant mtr alleles and azithromycin resistance. We find that the locus encompassing the mtrR transcriptional repressor and the mtrCDE pump is a hot spot of interspecific recombination introducing alleles from Neisseria meningitidis and Neisseria lactamica into N...
August 7, 2018: MBio
Prashant P Patil, Sanjeet Kumar, Samriti Midha, Vikas Gautam, Prabhu B Patil
Stenotrophomonas maltophilia has evolved as one of the leading multidrug-resistant pathogens responsible for a variety of nosocomial infections especially in highly debilitated patients. As information on the genomic and intraspecies diversity of this clinically important pathogen is limited, we sequenced the whole genome of 27 clinical isolates from hospitalized patients. Phylogenomic analysis along with the genomes of type strains suggested that the clinical isolates are distributed over the Stenotrophomonas maltophilia complex (Smc) within the genus Stenotrophomonas...
August 7, 2018: Microbial Genomics
Xiao-Yan Fan, Jing-Feng Gao, Kai-Ling Pan, Ding-Chang Li, Hui-Hui Dai, Xing Li
This study aimed to investigate the bacterial communities and antibiotic resistance genes (ARGs) in 16 wastewater treatment plants (WWTPs) treating municipal, industrial and mixed wastewater. Wastewater types showed obvious effects on bacterial communities and functions. Nitrosomonas, Nitrospira, Hyphomicrobium and Accumulibacter were the main functional genera. Mycobacterium was the dominant potential pathogens. A total of 69 ARGs were obtained, and the dominant ARGs subtypes were similar in different WWTPs...
July 25, 2018: Bioresource Technology
Gengqin Ma, Gaosheng Wu, Xiaofang Li, Hongxun Wang, Min Zhou
Ciprofloxacin, a broad-spectrum fluoroquinolone, is a bactericidal antibiotic targeting DNA gyrase and DNA topoisomerase IV encoded by the gyrA and parC genes. Resistance to fluoroquinolones requires the accumulation of multiple mutations including those that alter target genes and increase drug efflux. To examine the development of fluoroquinolones resistance in Vibrio parahaemolyticus, ciprofloxacin induction and selection was used to obtain several resistant V. parahaemolyticus mutants, which showed decreased susceptibilities to quinolones, and increased or decreased susceptibility to other structurally unrelated antibiotics...
August 3, 2018: Foodborne Pathogens and Disease
Tommaso Felicetti, Rolando Cannalire, Donatella Pietrella, Gniewomir Latacz, Annamaria Lubelska, Giuseppe Manfroni, Maria Letizia Barreca, Serena Massari, Oriana Tabarrini, Katarzyna J Kiec-Kononowicz, Bryan D Schindler, Glenn W Kaatz, Violetta Cecchetti, Stefano Sabatini
Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of non-antibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at sub-inhibitorial drug concentrations. Thus, efflux pump inhibitors (EPIs) offer a great opportunity to fight AMR. Given our experience in developing Staphylococcus aureus NorA EPIs, in this work, starting from the 2-phenylquinoline hit 1, we planned the introduction of methoxy groups on the basis of their presence in known NorA EPIs...
August 1, 2018: Journal of Medicinal Chemistry
Alevtina Mikhaylina, Amira Z Ksibe, David J Scanlan, Claudia A Blindauer
All organisms must regulate the cellular uptake, efflux, and intracellular trafficking of essential elements, including d-block metal ions. In bacteria, such regulation is achieved by the action of metal-responsive transcriptional regulators. Among several families of zinc-responsive transcription factors, the 'zinc uptake regulator' Zur is the most widespread. Zur normally represses transcription in its zinc-bound form, in which DNA-binding affinity is enhanced allosterically. Experimental and bioinformatic searches for Zur-regulated genes have revealed that in many cases, Zur proteins govern zinc homeostasis in a much more profound way than merely through the expression of uptake systems...
July 31, 2018: Biochemical Society Transactions
Brice E N Wamba, Armelle T Mbaveng, Paul Nayim, Joachim K Dzotam, Ornella J T Ngalani, Victor Kuete
Background: In this study, 18 methanol extracts from Cameroonian edible plants were tested for their antibacterial activities against 26 strains of S. aureus ; the role of efflux pumps in the resistance of tested bacteria and the antibiotic resistance-modulating activities against selected multidrug-resistant (MDR) phenotypes were also investigated. Methods: Broth microdilution assay was used to evaluate the antibacterial activity, the role of efflux pumps, and the antibiotic resistance-modulating effects of plant extracts...
2018: International Journal of Microbiology
Amanjot Kaur, Prince Sharma, Neena Capalash
Persisters are phenotypic variants of normal susceptible bacterial populations that survive prolonged exposure to high doses of antibiotics and are responsible for pertinacious infections and post-treatment relapses. Out of the three antibiotics, Acinetobacter baumannii formed the highest percentage of persister cells against rifampicin followed by amikacin and the least against colistin. Colistin-treated cells formed the high levels of reactive oxygen species (ROS) whose quenching with bipyridyl and thiourea led to an increased persister population...
July 23, 2018: Scientific Reports
Mohd W Azam, Asad U Khan
Pseudomonas aeruginosa is a pathogenic bacterial species that causes infections and diseases in both plants and animals, including several human diseases, especially in immune-compromised patients, and many hospital-acquired infections. Given that P. aeruginosa is an opportunistic pathogen, the occurrence of antimicrobial resistance makes it difficult to treat and eradicate. Antimicrobial resistance in P. aeruginosa is categorized as intrinsic, acquired, or adaptive. Here, we different aspects of resistance and pathogenicity in P...
July 20, 2018: Drug Discovery Today
Puttamas Nuonming, Sasimaporn Khemthong, Thanittra Dokpikul, Rojana Sukchawalit, Skorn Mongkolsuk
Agrobacterium tumefaciens AcrR is the transcriptional repressor of the acrABR operon. The AcrAB efflux pump confers resistance to various toxic compounds, including antibiotics [ciprofloxacin (CIP), nalidixic acid (NAL), novobiocin (NOV) and tetracycline (TET)], a detergent [sodium dodecyl sulfate (SDS)] and a biocide [triclosan (TRI)]. The sequence to which AcrR specifically binds in the acrA promoter region was determined by EMSA and DNase I footprinting. The AcrR-DNA interaction was abolished by adding NAL, SDS and TRI...
September 2018: Microbiological Research
Yvonne Agersø, Birgitte Stuer-Lauridsen, Karin Bjerre, Michelle Geervliet Jensen, Eric Johansen, Mads Bennedsen, Elke Brockmann, Bea Nielsen
Bacillus megaterium (n=29), Bacillus velezensis (n=26), Bacillus amyloliquefaciens (n=6), Bacillus paralicheniformis (n=28) and Bacillus licheniformis (n=35) strains from different sources, origins and time-periods were tested for the minimal inhibitory concentration (MIC) of nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C for 18-20 hours) as well as with a modified CLSI method (IST broth, 37°C (35°C for B. megaterium ), 24 hours). This allows a proposal of species-specific epidemiological cut-off values (ECOFFs) for interpretation of antimicrobial resistance in these species...
July 20, 2018: Applied and Environmental Microbiology
Joycy F S Dos Santos, Saulo R Tintino, Thiago S de Freitas, Fábia F Campina, Irwin R de A Menezes, José P Siqueira-Júnior, Henrique D M Coutinho, Francisco A B Cunha
Staphylococcus aureus has been reported as one of the most difficult to treat. In the search for new treatment alternatives, isolated plant substances such as phenolic compounds, have demonstrated the ability to reverse bacterial resistance. The present study aims to evaluate the inhibitory action of caffeic acid and gallic acid on efflux pumps from S. aureus resistant strains. The broth microdilution assay was carried out to obtain the MICs of caffeic acid and gallic acid while the efflux pump inhibition test was assessed through the reduction of the minimum inhibitory concentration of the antibiotic and ethidium bromide...
April 2018: Comparative Immunology, Microbiology and Infectious Diseases
Matej Remenár, Anna Kamlárová, Jana Harichová, Marcel Zámocký, Peter Ferianc
A bacterial isolate MR-CH-I2 [KC809939] isolated from soil contaminated mainly by high nickel concentrations in southwest Slovakia was previously found carrying nccA-like heavy-metal resistance determinant, marked as MR-CH-I2-HMR [KF218096]. According to phylogenetic analysis of short (696 bp) 16S rDNA (16S rRNA) sequences this bacterium was tentatively assigned to Uncultured beta proteobacterium clone GC0AA7ZA05PP1 [JQ913301]. nccA-like gene product was on the same base of its partial (581 bp) sequences tentatively assigned to CzcA family heavy metal efflux pump [YP_001899332] from Ralstonia picketii 12J with 99% similarity...
June 30, 2018: Polish Journal of Microbiology
Agnieszka Ewa Laudy
Non-antibiotic medicinal products consist of drugs with diverse activity against bacteria. Many non-antibiotics demonstrate direct anti-bacterial activity against Gram-positive cocci. The activity observed against Gram-negative rods is much lower and non-antibiotics primarily from the following groups: non-steroidal anti-inflammatory drugs, cardiovascular and antidepressant medicinal products demonstrate this activity. It has been shown that the low activity of some non-antibiotics or the absence of activity against Gram-negative rods is related, among other things, to the extrusion of these compounds from bacterial cells by multi-drug resistance efflux pumps...
June 30, 2018: Polish Journal of Microbiology
Pedro V Baptista, Matthew P McCusker, Andreia Carvalho, Daniela A Ferreira, Niamh M Mohan, Marta Martins, Alexandra R Fernandes
Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies...
2018: Frontiers in Microbiology
Rasmus N Klitgaard, Bimal Jana, Luca Guardabassi, Karen L Nielsen, Anders Løbner-Olesen
Ciprofloxacin is a potent antibacterial drug that is widely used in human clinical applications. As a consequence of its extensive use, resistance has emerged in almost all clinically relevant bacterial species. A mean to combat the observed ciprofloxacin resistance is by reversing it via co-administration of a potentiating compound, also known as a helper drug. Here, we report on the current advances in identifying ciprofloxacin helper drugs, and put them into perspective of our own findings. We searched for potential helper drug targets in Escherichia coli strains with different levels of ciprofloxacin resistance using transcriptomics i...
2018: Frontiers in Microbiology
Jia Guo, Xuan Zhang, Xiaorui Lu, Wenshuai Liu, Zhi Chen, Jilun Li, Linhong Deng, Ying Wen
The bacterial species Streptomyces avermitilis is an important industrial producer of avermectins, which are widely utilized as effective anthelmintic and insecticidal drugs. We used gene deletion, complementation, and overexpression experiments to identify SAV4189, a MarR-family transcriptional regulator (MFR) in this species, as an activator of avermectin biosynthesis. SAV4189 indirectly stimulated avermectin production by altering expression of cluster-situated activator gene aveR , and directly repressed the transcription of its own gene ( sav_4189 ) and adjacent cotranscribed gene sav_4190 (which encodes an unknown transmembrane efflux protein)...
2018: Frontiers in Microbiology
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