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https://www.readbyqxmd.com/read/29160808/interplay-between-colistin-resistance-virulence-and-fitness-in-acinetobacter-baumannii
#1
REVIEW
Gabriela Jorge Da Silva, Sara Domingues
Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an "old" antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM...
November 21, 2017: Antibiotics
https://www.readbyqxmd.com/read/29158274/dissemination-of-multidrug-resistant-proteus-mirabilis-clones-carrying-a-novel-integron-borne-blaimp-1-in-a-tertiary-hospital
#2
Ana Carolina Ramos, Rodrigo Cayô, Cecilia Godoy Carvalhaes, Thomas Jové, Greice Pereira da Silva, Fernanda Maciel Paschoin Sancho, Thomas Chagas-Neto, Eduardo Alexandrino Servolo Medeiros, Ana Cristina Gales
This study aimed to characterize multi-drug resistant P. mirabilis clones carrying a novel class 1 integron-borne blaIMP-1 In1359 was inserted into a large conjugative plasmid that also carried blaCTX-M-2 The production of carbapenemases in Enterobacteriaceae that are intrinsically resistant to polymyxins and tigecycline is very worrisome, representing a serious challenge to clinicians and infection control teams.
November 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29150371/emergence-of-polymyxin-b-resistance-in-a-polymyxin-b-susceptible-kpc-producing-klebsiella-pneumoniae-causing-bloodstream-infection-in-a-neutropenic-patient-during-polymyxin-b-therapy
#3
Alexandre P Zavascki, Raquel Girardello, Cibele M Magagnin, Laura C Antochevis, Rafael A Maciel, Jussara K Palmeiro, Ana C Gales
The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance)...
October 19, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29148380/high-rate-of-mcr-1-producing-escherichia-coli-and-klebsiella-pneumoniae-among-pigs-portugal
#4
Nicolas Kieffer, Marta Aires-de-Sousa, Patrice Nordmann, Laurent Poirel
The mcr-1 (mobile colistin resistance 1) gene, which encodes phosphoethanolamine transferase, has been recently identified as a source of acquired resistance to polymyxins in Escherichia coli. Using the SuperPolymyxin selective medium, we prospectively screened 100 pigs at 2 farms in Portugal for polymyxin-resistant Enterobacteriaceae and recovered 98 plasmid-mediated MCR-1-producing isolates. Most isolates corresponded to nonclonally related E. coli belonging to many sequence types; we also found 2 Klebsiella pneumoniae sequence types...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29147502/chemical-space-guided-discovery-of-antimicrobial-bridged-bicyclic-peptides-against-pseudomonas-aeruginosa-and-its-biofilms
#5
Ivan Di Bonaventura, Xian Jin, Ricardo Visini, Daniel Probst, Sacha Javor, Bee-Ha Gan, Gaëlle Michaud, Antonino Natalello, Silvia Maria Doglia, Thilo Köhler, Christian van Delden, Achim Stocker, Tamis Darbre, Jean-Louis Reymond
Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146285/rapid-polymyxin-np-test-for-the-detection-of-polymyxin-resistance-mediated-by-the-mcr-1-mcr-2-genes
#6
Laurent Poirel, Yu Larpin, Jan Dobias, Roger Stephan, Jean-Winoc Decousser, Jean-Yves Madec, Patrice Nordmann
The Rapid Polymyxin NP test has been recently developed to rapidly detect polymyxin resistance in Enterobacteriaceae. Here we evaluated this test for detecting MCR-1/MCR-2-producing Enterobacteriaceae using a collection of 70 non-redundant strains either recovered from the environment, animals, or humans. Sensitivity and specificity were found to be 100%.
September 22, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29138303/cxc-chemokines-exhibit-bactericidal-activity-against-multidrug-resistant-gram-negative-pathogens
#7
Matthew A Crawford, Debra J Fisher, Lisa M Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli, Tommaso Giani, Gian Maria Rossolini, Yohei Doi, David R Goodlett, Marc W Allard, Shashi K Sharma, Erum Khan, Robert K Ernst, Molly A Hughes
The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29136469/novel-linear-lipopeptide-paenipeptins-with-potential-for-eradicating-biofilms-and-sensitizing-gram-negative-bacteria-to-rifampicin-and-clarithromycin
#8
Sun Hee Moon, Xuan Zhang, Guangrong Zheng, Daniel G Meeker, Mark S Smeltzer, En Huang
We report the structure-activity relationship analyses of 17 linear lipopeptide paenipeptin analogues. Analogues 7, 12, and 17 were more potent than the lead compound. Analogue 17 was active against carbapenem-resistant and polymyxin-resistant pathogens. This compound at 40 μg/mL resulted in 3 log and 2.6 log reductions of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in catheter-associated biofilms in vitro. Analogue 17 showed little hemolysis at 32 μg/mL and lysed 11% of red blood cells at 64 μg/mL...
November 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29117525/membrane-cholesterol-reduces-polymyxin-b-nephrotoxicity-in-renal-membrane-analogs
#9
Adree Khondker, Richard J Alsop, Alexander Dhaliwal, Sokunthearath Saem, Jose M Moran-Mirabal, Maikel C Rheinstädter
Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29117270/screening-for-the-presence-of-mcr-1-mcr-2-genes-in-shiga-toxin-producing-escherichia-coli-recovered-from-a-major-produce-production-region-in-california
#10
Daniela Mavrici, Jaszemyn C Yambao, Bertram G Lee, Beatriz Quiñones, Xiaohua He
The rapid spreading of polymyxin E (colistin) resistance among bacterial strains through the horizontally transmissible mcr-1 and mcr-2 plasmids has become a serious concern. The emergence of these genes in Shiga toxin-producing Escherichia coli (STEC), a group of human pathogenic bacteria was even more worrisome, urging us to investigate the prevalence of mcr genes among STEC isolates. A total of 1000 STEC isolates, recovered from livestock, wildlife, produce and other environmental sources in a major production region for leafy vegetables in California during 2006-2014, were screened by PCR for the presence of plasmid-borne mcr-1 and mcr-2...
2017: PloS One
https://www.readbyqxmd.com/read/29114023/mcr-1-inhibition-with-peptide-conjugated-phosphorodiamidate-morpholino-oligomers-restores-sensitivity-to-polymyxin-in-escherichia-coli
#11
Seth M Daly, Carolyn R Sturge, Christina F Felder-Scott, Bruce L Geller, David E Greenberg
In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29107079/clonal-spread-of-carbapenem-resistant-acinetobacter-baumannii-in-neonatal-intensive-care-unit
#12
Wirlaine Glauce Maciel, Kesia Esther da Silva, Julio Croda, Rodrigo Cayô, Ana Carolina Ramos, Romário Oliveira de Sales, Gleyce Hellen de Almeida de Souza, José Victor Bortolotto Bampi, Leticia Cristina Limiere, Junior César Casagrande, Ana Cristina Gales, Simone Simionatto
Acinetobacter baumannii has been frequently associated with colonization and/or infection in neonatal intensive care units (NICU). In this study, we describe a clonal spread of carbapenem-resistant A. baumannii (CRAB) isolates in a NICU. A total of 21 CRAB isolates were collected from premature newborns. Only polymyxin B was active against such isolates. Nineteen CRAB isolates were clonally related (cluster C that belonged to worldwide-disseminated ST1). All newborns had peripheral access and previously received β-lactams therapy...
October 26, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29101229/-almg-responsible-for-polymyxin-resistance-in-pandemic-v-cholerae-is-a-glycyl-transferase-distantly-related-to-lipid-a-late-acyltransferases
#13
Jeremy C Henderson, Carmen M Herrera, M Stephen Trent
Cationic antimicrobial peptides (CAMPs), such as polymyxins are used as a last-line defense in treatment of many bacterial infections. However, some bacteria have developed resistance mechanisms to survive these compounds. Current pandemic O1 Vibrio cholerae biotype El Tor is resistant to polymyxins, whereas previous pandemic strain of the classical biotype is polymyxin sensitive. The almEFG operon found in El Tor V. cholerae confers >100-fold resistance to antimicrobial peptides through aminoacylation of lipopolysaccharide (LPS), expected to decrease the negatively charged surface of the V...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29094001/in-vitro-synergy-of-antibiotic-combinations-against-planktonic-and-biofilm-pseudomonas-aeruginosa
#14
Hossein Ghorbani, Mohammad Yousef Memar, Fatemeh Yeganeh Sefidan, Mina Yekani, Reza Ghotaslou
Aim: The combination of different antimicrobial agents and subsequent synergetic effects may be beneficial in treatment of P. aeruginosa infections. The aim of the present study was to determine antibiotic susceptibility patterns of clinical isolates of P. aeruginosa and the effect of different antibiotic combinations against the multidrug-resistant (MDR), biofilm-producing bacterium P. aeruginosa. Methods: Thirty-six P. aeruginosa clinical isolates were evaluated. The disk diffusion method was performed to determine antibiotic susceptibility patterns according to the Clinical and Laboratory Standards Institute (CLSI) guidelines...
2017: GMS Hygiene and Infection Control
https://www.readbyqxmd.com/read/29092042/expanding-the-potential-of-nai-107-for-treating-serious-eskape-pathogens-synergistic-combinations-against-gram-negatives-and-bactericidal-activity-against-non-dividing-cells
#15
Cristina Brunati, Thomas T Thomsen, Eleonora Gaspari, Sonia Maffioli, Margherita Sosio, Daniela Jabes, Anders Løbner-Olesen, Stefano Donadio
Objectives: To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce self-resistance in Gram-positive bacteria. Methods: We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms...
October 30, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091226/plazomicin-activity-against-polymyxin-resistant-enterobacteriaceae-including-mcr-1-producing-isolates
#16
Valérie Denervaud-Tendon, Laurent Poirel, Lynn E Connolly, Kevin M Krause, Patrice Nordmann
Objectives: Plazomicin, a novel aminoglycoside with in vitro activity against MDR Gram-negative organisms, is under development to treat patients with serious enterobacterial infections. We evaluated the activity of plazomicin and comparators against colistin-resistant enterobacterial isolates. Methods: Susceptibility to plazomicin and comparators was tested by broth microdilution for a collection of 95 colistin-resistant enterobacterial isolates collected from 29 hospitals in eight countries...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091202/pointfinder-a-novel-web-tool-for-wgs-based-detection-of-antimicrobial-resistance-associated-with-chromosomal-point-mutations-in-bacterial-pathogens
#17
Ea Zankari, Rosa Allesøe, Katrine G Joensen, Lina M Cavaco, Ole Lund, Frank M Aarestrup
Background: Antibiotic resistance is a major health problem, as drugs that were once highly effective no longer cure bacterial infections. WGS has previously been shown to be an alternative method for detecting horizontally acquired antimicrobial resistance genes. However, suitable bioinformatics methods that can provide easily interpretable, accurate and fast results for antimicrobial resistance associated with chromosomal point mutations are still lacking. Methods: Phenotypic antimicrobial susceptibility tests were performed on 150 isolates covering three different bacterial species: Salmonella enterica, Escherichia coli and Campylobacter jejuni...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091193/mcr-2-mediated-plasmid-borne-polymyxin-resistance-most-likely-originates-from-moraxella-pluranimalium
#18
Laurent Poirel, Nicolas Kieffer, José F Fernandez-Garayzabal, Ana Isabel Vela, Yu Larpin, Patrice Nordmann
No abstract text is available yet for this article.
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091192/modifications-in-the-pmrb-gene-are-the-primary-mechanism-for-the-development-of-chromosomally-encoded-resistance-to-polymyxins-in-uropathogenic-escherichia-coli
#19
Minh-Duy Phan, Nguyen Thi Khanh Nhu, Maud E S Achard, Brian M Forde, Kar Wai Hong, Teik Min Chong, Wai-Fong Yin, Kok-Gan Chan, Nicholas P West, Mark J Walker, David L Paterson, Scott A Beatson, Mark A Schembri
Objectives: Polymyxins remain one of the last-resort drugs to treat infections caused by MDR Gram-negative pathogens. Here, we determined the mechanisms by which chromosomally encoded resistance to colistin and polymyxin B can arise in the MDR uropathogenic Escherichia coli ST131 reference strain EC958. Methods: Two complementary approaches, saturated transposon mutagenesis and spontaneous mutation induction with high concentrations of colistin and polymyxin B, were employed to select for mutations associated with resistance to polymyxins...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29079699/substrate-analog-interaction-with-mcr-1-offers-insight-into-the-rising-threat-of-the-plasmid-mediated-transferable-colistin-resistance
#20
Pengcheng Wei, Guangji Song, Mengyang Shi, Yafei Zhou, Yang Liu, Jun Lei, Peng Chen, Lei Yin
Colistin is considered a last-resort antibiotic against most gram-negative bacteria. Recent discoveries of a plasmid-mediated, transferable colistin-resistance gene (mcr-1) on all continents have heralded the imminent emergence of pan-drug-resistant superbacteria. The inner-membrane protein MCR-1 can catalyze the transfer of phosphoethanolamine (PEA) to lipid A, resulting in colistin resistance. However, little is known about the mechanism, and few drugs exist to address this issue. We present crystal structures revealing the MCR-1 catalytic domain (cMCR-1) as a monozinc metalloprotein with ethanolamine (ETA) and d-glucose, respectively, thus highlighting 2 possible substrate-binding pockets in the MCR-1-catalyzed PEA transfer reaction...
October 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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