Clamping down on drugs: the Escherichia coli multidrug efflux protein MdtM
Publication date: Available online 27 September 2017Source: Research in MicrobiologyAuthor(s): Christopher J. Law, Kamela O. AlegreAbstractMultidrug resistance is principally a consequence of the active transport of drugs out of the cell by proteins that are integral membrane transporters. In the following review, we present a synthesis of current understanding of the Escherichia coli multidrug resistance transporter, MdtM, a 410 amino acid residue protein that belongs to the large and ubiquitous major facilitator superfamily (MFS). (Source: Research in Microbiology)
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Regulation of the AcrAB-TolC efflux pump in Enterobacteriaceae
Publication date: Available online 8 November 2017Source: Research in MicrobiologyAuthor(s): Natasha Weston, Prateek Sharma, Vito Ricci, Laura J.V. PiddockAbstractBacterial multidrug efflux systems are a major mechanism of antimicrobial resistance and are fundamental to the physiology of Gram-negative bacteria. The resistance-nodulation-division (RND) family of efflux pumps is the most clinically significant, as it is associated with multidrug resistance. Expression of efflux systems is subject to multiple levels of regulation, involving local and global transcriptional regulation as well as post-transcriptional and post-t...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
The hydrophobic trap—the Achilles heel of RND efflux pumps
Publication date: Available online 13 November 2017Source: Research in MicrobiologyAuthor(s): Zachary Aron, Timothy J. OppermanAbstractResistance–nodulation–division (RND) superfamily efflux pumps play a major role in multidrug resistance (MDR) of Gram-negative pathogens by extruding diverse classes of antibiotics from the cell. There has been considerable interest in developing efflux pump inhibitors (EPIs) of RND pumps as adjunctive therapies. The primary challenge in EPI discovery has been the highly hydrophobic, poly-specific substrate binding site of the target. Recent findings have identified the hydrophobic trap...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Extension of the transposable bacterial virus family: two genomic organisations among phages and prophages with a Tn552-related transposase
Publication date: Available online 20 November 2017Source: Research in MicrobiologyAuthor(s): Ariane Toussaint, Frédérique Van GijsegemAbstractMu-like transposable phages and prophages have been isolated from, or predicted, in a wide range of bacterial phyla. However, related B3-like transposable phages, which differ in their genome organisation and the DDE transposase and transposition activator they code for have thus far been restricted to a very limited set of hosts. Through sequence similarity searches, we have now expanded the number of predicted B3-like prophages and uncovered a third genomic organisation. These n...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Reconstitution of the activity of RND efflux pumps: a “bottom-up” approach
We present possible lines of improvement for the study of such systems and provide insights into future goals and challenges of efflux pump reconstitution and transport. (Source: Research in Microbiology)
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Fluorescence enlightens RND pump activity and the intrabacterial concentration of antibiotics
Publication date: Available online 5 December 2017Source: Research in MicrobiologyAuthor(s): Muriel Masi, Estelle Dumont, Julia Vergalli, Jelena Pajovic, Matthieu Réfrégiers, Jean-Marie PagèsAbstractTo understand antibiotic resistance in Gram-negative bacteria, a key point is to investigate antibiotic accumulation, which is defined by influx and efflux. Several methods exist to evaluate membrane permeability and efflux pump activity, but they present disadvantages and limitations. An optimized spectrofluorimetric method using intrinsic tryptophan fluorescence as an internal standard, as well as a complementary microfluo...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Computer simulations of the activity of RND efflux pumps
Publication date: Available online 31 January 2018Source: Research in MicrobiologyAuthor(s): Attilio Vittorio Vargiu, Venkata Krishnan Ramaswamy, Giuliano Malloci, Ivana Malvacio, Alessio Atzori, Paolo RuggeroneAbstractThe putative mechanism by which bacterial RND-type multidrug efflux pumps recognize and transport their substrates is a complex and fascinating enigma of structural biology. How a single protein can recognize a huge number of unrelated compounds and transport them through one or just a few mechanisms is an amazing feature not yet completely unveiled. The appearance of cooperativity further complicates the un...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Pacing across the membrane: the novel PACE family of efflux pumps is widespread in Gram-negative pathogens
Publication date: Available online 2 February 2018Source: Research in MicrobiologyAuthor(s): Karl A. Hassan, Qi Liu, Liam D.H. Elbourne, Irshad Ahmad, David Sharples, Varsha Naidu, Chak Lam Chan, Liping Li, Steven P.D. Harborne, Alaska Pokhrel, Vincent L.G. Postis, Adrian Goldman, Peter J.F. Henderson, Ian T. PaulsenAbstractThe proteobacterial antimicrobial compound efflux (PACE) family of transport proteins was only recently described. PACE family transport proteins can confer resistance to a range of biocides used as disinfectants and antiseptics, and are encoded by many important Gram-negative human pathogens. However, ...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes
Publication date: Available online 9 February 2018Source: Research in MicrobiologyAuthor(s): Timothy Travers, Katherine J. Wang, Cesar A. López, S. GnanakaranAbstractGram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this review, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite ...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier
Publication date: Available online 16 February 2018Source: Research in MicrobiologyAuthor(s): Helen I. Zgurskaya, Valentin V. Rybenkov, Ganesh Krishnamoorthy, Inga V. LeusAbstractAntibiotic resistance is a serious threat to public health. Significant efforts are currently directed toward containment of the spread of resistance, finding new therapeutic options concerning resistant human and animal pathogens, and addressing the gaps in the fundamental understanding of mechanisms of resistance. Experimental data and kinetic modeling revealed a major factor in resistance, the synergy between active efflux and the low permeabil...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
The Escherichia coli effluxome
Publication date: Available online 21 March 2018Source: Research in MicrobiologyAuthor(s): Shimon SchuldinerAbstractMultidrug transporters function in a coordinated mode to provide an essential first-line defense mechanism that prevents antibiotics from reaching 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 xenobi...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
RND transporters in the living world
Publication date: Available online 22 March 2018Source: Research in MicrobiologyAuthor(s): Hiroshi NikaidoAbstractTransporters of the RND superfamily are well-known as the major drug efflux pumps of Gram-negative bacteria. However, they are widespread in organisms ranging from Archaea to Eukaryotes, and perform diverse functions. This review gives a brief overview of these diverse members of the superfamily with emphasis on their structure and functions. (Source: Research in Microbiology)
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Antibiofilm activity of bioactive hop compounds humulone, lupulone and xanthohumol toward susceptible and resistant staphylococci
Publication date: April 2018Source: Research in Microbiology, Volume 169, Issue 3Author(s): Katerina Bogdanova, Magdalena Röderova, Milan Kolar, Katerina Langova, Martin Dusek, Petr Jost, Klara Kubelkova, Pavel Bostik, Jana OlsovskaAbstractBacterial biofilms pose a serious medical problem due to their significant resistance to antimicrobials, and staphylococci are recognized as the most frequent cause of biofilm-associated infections. The hop plant (Humulus lupulus L.) contains substances that have been determined to act as anti-infective agents against bacteria, mainly in planktonic form. Therefore, we decided to investi...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Functional characterization of the Sporothrix schenckii Ktr4 and Ktr5, mannosyltransferases involved in the N-linked glycosylation pathway
Publication date: April 2018Source: Research in Microbiology, Volume 169, Issue 3Author(s): Luz A. López-Ramírez, Nahúm V. Hernández, Nancy E. Lozoya-Pérez, Leila M. Lopes-Bezerra, Héctor M. Mora-MontesAbstractSporothrix schenckii is one of the causative agents of the deep-seated mycosis sporotrichosis, a fungal infection with worldwide distribution. Fungus-specific molecules and biosynthetic pathways are potential targets for the development of new antifungal drugs. The MNT1/KRE2 gene family is a group of genes that encode fungus-specific Golgi-resident mannosyltransferases that participate in the synthesis of O-lin...
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection
Publication date: April 2018Source: Research in Microbiology, Volume 169, Issue 3Author(s): Yi-Ling Lo, Chyi-Liang Chen, Lunda Shen, Ying-Ching Chen, Yi-Hsin Wang, Chung-Chan Lee, Lian-Chen Wang, Chih-Hsien Chuang, Rajendra Prasad Janapatla, Cheng-Hsun Chiu, Hwan-You ChangAbstractFliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant....
Source: Research in Microbiology - July 10, 2018 Category: Microbiology Source Type: research
