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biofilm and efflux pump

Yoshinori Sato, Yuka Unno, Tsuneyuki Ubagai, Yasuo Ono
We investigated the numbers of planktonic and biofilm cells and the expression levels of genes encoding efflux pumps and biofilm-related proteins in 10 clinical isolates of multi-drug resistant Acinetobacter baumannii (MDRA) as well as in its standard strain ATCC 19606 in the presence of colistin (CST), polymyxin B (PMB), minomycin (MIN), and tigecycline (TGC) at their respective sub-MICs. The number of planktonic and biofilm cells of ATCC 19606 decreased in the presence of all aforementioned antibiotics in a dose-dependent manner...
2018: PloS One
Ilyas Alav, J Mark Sutton, Khondaker Miraz Rahman
Efflux pumps are widely implicated in antibiotic resistance because they can extrude the majority of clinically relevant antibiotics from within cells to the extracellular environment. However, there is increasing evidence from many studies to suggest that the pumps also play a role in biofilm formation. These studies have involved investigating the effects of efflux pump gene mutagenesis and efflux pump inhibitors on biofilm formation, and measuring the levels of efflux pump gene expression in biofilms. In particular, several key pathogenic species associated with increasing multidrug resistance, such as Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, have been investigated, whilst other studies have focused on Salmonella enterica serovar Typhimurium as a model organism and problematic pathogen...
February 28, 2018: Journal of Antimicrobial Chemotherapy
Valerie Defraine, Veerle Liebens, Evelien Loos, Toon Swings, Bram Weytjens, Carolina Fierro, Kathleen Marchal, Liam Sharkey, Alex J O'Neill, Romu Corbau, Arnaud Marchand, Patrick Chaltin, Maarten Fauvart, Jan Michiels
The ever increasing multidrug-resistance of clinically important pathogens and the lack of novel antibiotics have resulted in a true antibiotic crisis where many antibiotics are no longer effective. Further complicating the treatment of bacterial infections are antibiotic-tolerant persister cells. Besides being responsible for the recalcitrant nature of chronic infections, persister cells greatly contribute to the observed antibiotic tolerance in biofilms and even facilitate the emergence of antibiotic resistance...
2018: Frontiers in Microbiology
Sushovan Dam, Jean-Marie Pagès, Muriel Masi
Bacteria have evolved several strategies to survive a myriad of harmful conditions in the environment and in hosts. In Gram-negative bacteria, responses to nutrient limitation, oxidative or nitrosative stress, envelope stress, exposure to antimicrobials and other growth-limiting stresses have been linked to the development of antimicrobial resistance. This results from the activation of protective changes to cell physiology (decreased outer membrane permeability), resistance transporters (drug efflux pumps), resistant lifestyles (biofilms, persistence) and/or resistance mutations (target mutations, production of antibiotic modification/degradation enzymes)...
January 25, 2018: Microbiology
S Dižová, H Bujdáková
Farnesol is a quorum sensing (QS) molecule synthesized by Candida albicans acting as a negative regulator of morphogenesis; it blocks the yeast-to-hyphae transformation. This molecule is currently studied in particular from the viewpoint of possible use as a substance with anticancer properties and with an antimicrobial, and anti-biofilm effect in yeasts resistant or tolerant to conventional therapeutic agents, for example fluconazole. Besides the aforementioned effect on morphological transformation through cyclic AMP (cAMP)/protein kinase A (cAMP-PKA) pathway, it also affects other biochemical pathways of yeasts, for example those ones for sterol biosynthesis or triggering of apoptosis via accumulation of ROS (reactive oxygen species) that damage essential cellular compartments...
June 1, 2017: Die Pharmazie
Atul Munish Chander, Rakesh Kochhar, Devinder Kumar Dhawan, Sanjay Kumar Bhadada, Shanmugam Mayilraj
Background: Janibacter melonis and other member of this genus are known to cause bacteremia and serious clinical comorbidities, but there is no study reporting about pathogenicity attributes of J. melonis. Janibacter terrae is known to cause lethal infection. Reporting the genome of J. melonis CD11-4 and comparative genomics with other members of genus has provided some novel insights that can enable us to understand the mechanisms responsible for its pathogenicity in humans. Results: Comparative genomic analysis by Rapid Annotation Server and Technology revealed the presence of similar virulence determinant genes in both J...
2018: Gut Pathogens
Cynthia A Danquah, Eleftheria Kakagianni, Proma Khondkar, Arundhati Maitra, Mukhlesur Rahman, Dimitrios Evangelopoulos, Timothy D McHugh, Paul Stapleton, John Malkinson, Sanjib Bhakta, Simon Gibbons
Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1)...
January 18, 2018: Scientific Reports
Ruoyi Hua, Yun Xia, Wenyao Wu, Jia Yan, Mi Yang
Linezolid is an oxazolidinone antibiotic commonly used to treat serious infections caused by vancomycin-resistant enterococcus. Recently, low-level linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the resistant mechanisms remain undefined. Whole-transcriptome profiling was performed on an E. faecalis strain P10748 with low-level linezolid resistance in comparison with a linezolid-susceptible strain 3138 and the standard control strain ATCC29212. The functions of differentially expressed genes (DEGs) were predicted, with some DEGs potentially involved in drug resistance were validated by PCR and quantitative PCR (qPCR)...
January 8, 2018: Gene
Nanbiao Long, Liping Zeng, Shanlei Qiao, Lei Li, Guowei Zhong
Antifungal treatment is often ineffectual, which is partly contributed by biofilm. In this study, combined forward and reverse genetics strategy, we identified the nucleus-localized AfSsn3 and its partner AfSsn8, which constituting a cdk8-cyclin pair, are required for azole resistance in Aspergillus fumigatus Deletion of Afssn3 led to increased absorption and utilization of glucose and amino acids. Interestingly, absorption and utilization of glucose accelerated the extracellular polysaccharide formation, while utilization of the amino acids serine, threonine and glycine increased sphingolipid pathway intermediates accumulation...
January 8, 2018: Antimicrobial Agents and Chemotherapy
Bandita Poudyal, Karin Sauer
A hallmark of biofilms is their tolerance to killing by antimicrobial agents. In Pseudomonas aeruginosa , biofilm drug tolerance requires the c-di-GMP-responsive MerR transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm drug tolerance has not been elucidated. Here, we demonstrate that BrlR activates the expression of at least 7 ABC transport systems, including the PA1874-PA1875-PA1876-PA1877 (PA1874-77) operon, with chromatin immunoprecipitation and DNA binding assays confirming BrlR binding to the promoter region of PA1874-77...
February 2018: Antimicrobial Agents and Chemotherapy
Xinning Liu, Tao Li, Decai Wang, Yilei Yang, Wenwen Sun, Jianqiao Liu, Shujuan Sun
Candida albicans ( C. albicans ) is one of the important opportunistic fungal pathogens that is closely associated with disseminated or chronic infections. The objective of this study is to evaluate the synergistic antifungal effect of licofelone, which is dual microsomal prostaglandin E2 synthase/lipoxygenase (mPGES-1/LOX) inhibitor in combination with fluconazole against C. albicans . Here our results showed that licofelone (16 μg/mL) can synergistically work with fluconazole (1 μg/mL) against planktonic cells of fluconazole-resistant C...
2017: Frontiers in Microbiology
Lucas Chaves, Lísia Moura Tomich, Matias Salomão, Gleice Cristina Leite, Jessica Ramos, Roberta Ruedas Martins, Camila Rizek, Patricia Neves, Marjorie Vieira Batista, Ulysses Amigo, Thais Guimaraes, Anna Sara Levin, Silvia Figueiredo Costa
PURPOSE: Carbapenem resistance in P. aeruginosa is increasing worldwide. In Brazil, SPM-1 is the main P. aeruginosa carbapenemase identified. Little is known about the virulence factor in SPM-1 clones.Methodolgy. We describe a carbapenem-resistant P. aeruginosa bloodstream infection (CRPa-BSI) outbreak in a bone marrow transplant Unit (BMT). Twenty-nine CRPa-BSI cases were compared to 58 controls. Microbiological characteristics of isolates, such as sensitivity, carbapenemase gene PCR for P...
December 2017: Journal of Medical Microbiology
Samsher Singh, Nitin P Kalia, Prashant Joshi, Ajay Kumar, Parduman R Sharma, Ashok Kumar, Sandip B Bharate, Inshad A Khan
This study elucidated the role of boeravinone B, a NorA multidrug efflux pump inhibitor, in biofilm inhibition. The effects of boeravinone B plus ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild-type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758, respectively). The mechanism of action was confirmed using the ethidium bromide accumulation and efflux assay. The role of boeravinone B as a human P-glycoprotein (P-gp) inhibitor was examined in the LS-180 (colon cancer) cell line...
2017: Frontiers in Microbiology
Evangelos I Kazakos, Nick Dorrell, Stergios A Polyzos, Georgia Deretzi, Jannis Kountouras
Attaran et al([1]) have recently shown that decreased susceptibility of established Helicobacter pylori (H. pylori) biofilms to specific antibiotics, was associated with the overtly enhanced transcription of two efflux pump genes, hp1165 and hefA, involved in specific resistance to tetracycline and multiple antibiotics, respectively. Apart from antibiotic exposure, secretion of multiple antimicrobial peptides, such as human β-defensins (hβDs), by the gastric epithelium upon Hp challenge, may act as early triggering events that positively impact biofilm formation and thus, antibiotic resistance...
September 7, 2017: World Journal of Gastroenterology: WJG
Jannik Donner, Michael Reck, Boyke Bunk, Michael Jarek, Constantin Benjamin App, Jan P Meier-Kolthoff, Jörg Overmann, Rolf Müller, Andreas Kirschning, Irene Wagner-Döbler
The myxobacterial secondary metabolite carolacton inhibits growth of Streptococcus pneumoniae and kills biofilm cells of the caries- and endocarditis-associated pathogen Streptococcus mutans at nanomolar concentrations. Here, we studied the response to carolacton of an Escherichia coli strain that lacked the outer membrane protein TolC. Whole-genome sequencing of the laboratory E. coli strain TolC revealed the integration of an insertion element, IS5, at the tolC locus and a close phylogenetic relationship to the ancient E...
September 2017: MSphere
Hemant Kumar Gupta, Shruti Shrivastava, Rakesh Sharma
Ca(2+) plays an important role in the physiology of bacteria. Intracellular Ca(2+) concentrations are tightly maintained in the nanomolar range. Molecular mechanisms of Ca(2+) uptake in bacteria remain elusive. Here we show that CtpE is responsible for Ca(2+) uptake in Mycobacterium smegmatis It represents a previously uncharacterized P-type ATPase family in bacteria. Disruption of ctpE in M. smegmatis resulted in a mutant with impaired growth under Ca(2+)-deficient conditions. The growth defect of the mutant could be rescued by Ca(2+) or by ectopic expression of ctpE from M...
September 26, 2017: MBio
Mengjiao Lu, Cuixiang Yu, Xueyan Cui, Jinyi Shi, Lei Yuan, Shujuan Sun
Candida spp. are the primary opportunistic pathogens of nosocomial fungal infections, causing both superficial and life-threatening systemic infections. Combination therapy for fungal infections has attracted considerable attention, especially for those caused by drug-resistant fungi. Gentamicin (GM), an aminoglycoside antibiotic, has weak antifungal activity against Fusarium spp. The aim of this study was to investigate the interactions of GM with azoles against Candida spp. and the underlying mechanisms. In a chequerboard assay, GM was found not only to work synergistically with azoles against planktonic cells of drug-resistant Candida albicans with a fractional inhibitory concentration index (FICI) of 0...
January 2018: International Journal of Antimicrobial Agents
Jonathan Nzakizwanayo, Paola Scavone, Shirin Jamshidi, Joseph A Hawthorne, Harriet Pelling, Cinzia Dedi, Jonathan P Salvage, Charlotte K Hind, Fergus M Guppy, Lara M Barnes, Bhavik A Patel, Khondaker M Rahman, Mark J Sutton, Brian V Jones
Proteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urine flow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in P. mirabilis, and control crystalline biofilm formation...
September 22, 2017: Scientific Reports
Ana Vieira, Amritha Ramesh, Alan M Seddon, Andrey V Karlyshev
Campylobacter jejuni is a foodborne pathogen recognized as the leading cause of human bacterial gastroenteritis. The wide use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter In addition to a role in multidrug resistance, the Campylobacter CmeABC RND-type efflux pump, which is associated with multidrug resistance (MDR), may also be involved in virulence. As a vehicle of pathogenic microorganisms, the protozoan Acanthamoeba is a good model for the investigation of bacterial survival in the environment and molecular mechanisms of pathogenicity...
September 15, 2017: Applied and Environmental Microbiology
Eric F Kong, Christina Tsui, Sona Kucharíková, Patrick Van Dijck, Mary Ann Jabra-Rizk
In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum sensing molecule secreted by the fungal species Candida albicans and shown to play a central physiological role during fungal biofilm growth. Our pervious in vitro and in vivo studies characterized an intricate interaction between C. albicans and the bacterial pathogen Staphylococcus aureus , as these species coexist in biofilm. In this study, we aimed to investigate the impact of farnesol on S...
December 2017: Antimicrobial Agents and Chemotherapy
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