scholarly journals “Clicking” an Ionic Liquid to a Potent Antimicrobial Peptide: On the Route towards Improved Stability

2020 ◽  
Vol 21 (17) ◽  
pp. 6174
Author(s):  
Ana Gomes ◽  
Lucinda J. Bessa ◽  
Patrícia Correia ◽  
Iva Fernandes ◽  
Ricardo Ferraz ◽  
...  
Keyword(s):  
Ionic Liquid ◽  
Ionic Liquids ◽  
Klebsiella Pneumoniae ◽  
Antimicrobial Peptide ◽  
Clinical Isolate ◽  
Bioactive Peptides ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Improved Stability

A covalent conjugate between an antibacterial ionic liquid and an antimicrobial peptide was produced via “click” chemistry, and found to retain the parent peptide’s activity against multidrug-resistant clinical isolates of Gram-negative bacteria, and antibiofilm action on a resistant clinical isolate of Klebsiella pneumoniae, while exhibiting much improved stability towards tyrosinase-mediated modifications. This unprecedented communication is a prelude for the promise held by ionic liquids -based approaches as tools to improve the action of bioactive peptides.

scholarly journals A Molecular Perspective on Colistin and Klebsiella pneumoniae: Mode of Action, Resistance Genetics, and Phenotypic Susceptibility

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1165
Author(s):  
Rita Elias ◽  
Aida Duarte ◽  
João Perdigão
Keyword(s):  
Klebsiella Pneumoniae ◽  
Mode Of Action ◽  
Lipid A ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Drug Susceptibility Testing ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative

Klebsiella pneumoniae is a rod-shaped, encapsulated, Gram-negative bacteria associated with multiple nosocomial infections. Multidrug-resistant (MDR) K. pneumoniae strains have been increasing and the therapeutic options are increasingly limited. Colistin is a long-used, polycationic, heptapeptide that has regained attention due to its activity against Gram-negative bacteria, including the MDR K. pneumoniae strains. However, this antibiotic has a complex mode of action that is still under research along with numerous side-effects. The acquisition of colistin resistance is mainly associated with alteration of lipid A net charge through the addition of cationic groups synthesized by the gene products of a multi-genic regulatory network. Besides mutations in these chromosomal genes, colistin resistance can also be achieved through the acquisition of plasmid-encoded genes. Nevertheless, the diversity of molecular markers for colistin resistance along with some adverse colistin properties compromises the reliability of colistin-resistance monitorization methods. The present review is focused on the colistin action and molecular resistance mechanisms, along with specific limitations on drug susceptibility testing for K. pneumoniae.

scholarly journals IS26 mediate the acquisition of tigecycline resistance gene cluster tmexCD1-toprJ1 by IncHI1B-FIB plasmids in Klebsiella pneumoniae and Klebsiella quasipneumoniae from food market sewage

2020 ◽  
Author(s):  
Miao Wan ◽  
Xun Gao ◽  
Luchao Lv ◽  
Zhongpeng Cai ◽  
Jian-Hua Liu
Keyword(s):  
Klebsiella Pneumoniae ◽  
Gene Cluster ◽  
Resistance Gene ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Resistance Gene Cluster ◽  
Carbapenem Resistant ◽  
Food Market ◽  
Carbapenem Resistant Enterobacteriaceae

Tigecycline and colistin are considered 20 as the final options for the treatment of infections caused by multidrug-resistant (MDR) gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae (1).…

Combating multidrug-resistant Gram-negative bacteria with structurally nanoengineered antimicrobial peptide polymers

2016 ◽  
Vol 1 (11) ◽  
Author(s):  
Shu J. Lam ◽  
Neil M. O'Brien-Simpson ◽  
Namfon Pantarat ◽  
Adrian Sulistio ◽  
Edgar H. H. Wong ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Peptide Polymers

scholarly journals Plasmids Shape the Current Prevalence of tmexCD1-toprJ1 among Klebsiella pneumoniae in Food Production Chains

mSystems ◽  
2021 ◽  
Author(s):  
Kai Peng ◽  
Qian Wang ◽  
Yi Yin ◽  
Yan Li ◽  
Yuan Liu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Human Health ◽  
Food Production ◽  
Antibacterial Agents ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Current Prevalence

Tigecycline, the first member of the glycylcycline class of antibacterial agents, is frequently used to treat complicated infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria. The emergence of a novel plasmid-mediated efflux pump, TmexCD1-ToprJ1, conferring resistance to multiple antimicrobials, including tigecycline, poses a huge risk to human health.

scholarly journals In vitro evolution of colistin resistance in the Klebsiella pneumoniae complex follows multiple evolutionary trajectories with variable effects on fitness and virulence characteristics

2020 ◽  
Author(s):  
Axel B. Janssen ◽  
Dennis J. Doorduijn ◽  
Grant Mills ◽  
Malbert R.C. Rogers ◽  
Marc J.M. Bonten ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Lipid A ◽  
Multidrug Resistant ◽  
Sensu Stricto ◽  
Cross Resistance ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Evolutionary Trajectories

AbstractThe increasing prevalence of multidrug-resistant Gram-negative opportunistic pathogens, including Klebsiella pneumoniae, has led to a resurgence in the use of colistin as a last-resort drug. Colistin is a cationic lipopeptide antibiotic that selectively acts on Gram-negative bacteria through electrostatic interactions with anionic phosphate groups of the lipid A moiety of lipopolysaccharides (LPS). Colistin resistance in K. pneumoniae is mediated through loss of these phosphate groups, or modification with cationic groups (e.g. 4-amino-4-deoxy-L-arabinose (L-Ara4N), or phosphoethanolamine), but also hydroxylation of acyl-groups of lipid A. Here, we study the in vitro evolutionary trajectories towards colistin resistance in clinical K. pneumoniae complex strains (three K. pneumoniae sensu stricto strains and one K. variicola subsp. variicola strain) and their impact on fitness and virulence characteristics.Through population sequencing during the in vitro evolution experiment, we found that resistance develops through a combination of single nucleotide polymorphisms (SNPs), insertion and deletions (indels), and the integration of insertion sequence (IS) elements, affecting genes associated with LPS biosynthesis and modification, and capsule structures. The development of colistin resistance decreased the maximum growth rate of one K. pneumoniae sensu stricto strain, but not in the other three K. pneumoniae sensu lato strains. Colistin-resistant strains had lipid A modified through hydroxylation, palmitoylation, and L-Ara4N addition. Colistin-resistant K. pneumoniae sensu stricto strains exhibited cross-resistance to LL-37, in contrast to the K. variicola subsp. variicola strain that did not change in susceptibility to LL-37. Virulence, as determined in a Caenorhabditis elegans survival assay, was higher in two colistin-resistant strains.Our study suggests that nosocomial K. pneumoniae complex strains can rapidly develop colistin resistance de novo through diverse evolutionary trajectories upon exposure to colistin. This effectively shortens the lifespan of this last-resort antibiotic for the treatment of infections with multidrug-resistant Klebsiella.Author summaryBacteria that frequently cause infections in hospitalised patients are becoming increasingly resistant to antibiotics. Colistin is a positively charged antibiotic that is used for the treatment of infections with multidrug-resistant Gram-negative bacteria. Colistin acts by specifically interacting with the negatively charged LPS molecule in the outer membrane of Gram-negative bacteria. Colistin resistance is mostly mediated through modification of LPS to reduce its negative charge. Here, we use a laboratory evolution experiment to show that strains belonging to the Klebsiella pneumoniae complex, a common cause of multidrug-resistant hospital-acquired infections, can rapidly accumulate mutations that reduce the negative charge of LPS without an appreciable loss of fitness. Colistin resistance can lead to cross-resistance to an antimicrobial peptide of the human innate immune system, but can increase susceptibility to serum, and virulence in a nematode model. These findings show that extensively resistant K. pneumoniae complex strains may rapidly develop resistance to the last-resort antibiotic colistin via different evolutionary trajectories, while retaining their ability to cause infections.

scholarly journals Complete Genome Sequence of a Colistin-Resistant Klebsiella pneumoniae Isolate from Houseflies (Musca domestica) in a Trash Disposal Truck in the United States

2020 ◽  
Vol 9 (22) ◽  
Author(s):  
Anwar Kalalah ◽  
Anil Poudel ◽  
Jiansen Gong ◽  
Li Chen ◽  
Yi Yang ◽  
...  
Keyword(s):  
United States ◽  
Klebsiella Pneumoniae ◽  
Genome Sequencing ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
The United States ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACT A Klebsiella pneumoniae strain isolated from houseflies in a trash disposal truck in the United States was resistant to colistin, a last-resort drug for treating infections caused by multidrug-resistant Gram-negative bacteria. Complete genome sequencing resulted in a total genome size of 5,337,408 bp for this isolate with a plasmid of 224,442 bp.

scholarly journals Development of a novel antimicrobial peptide AWRK6

2016 ◽  
Vol 11 (2) ◽  
pp. 460 ◽  
Author(s):  
Dusik  Kim ◽  
Zheng  Wang ◽  
Lili  Jin ◽  
Hanpin  Li ◽  
Junwei  Hwang ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Antimicrobial Activities ◽  
Gram Negative Bacteria ◽  
Bacterial Strains ◽  
Gram Negative ◽  
Killing Rate ◽  
Physiological Conditions ◽  
Alkaline Environments ◽  
Improved Stability ◽  
Rana Dybowskii

<p class="Abstract">We have previously identified an antimicrobial peptide called dybowskin2-CDYa (Dy2) in the cutaneous secretion from the Chinese frog Rana dybowskii. In this study, we used Dy2 as a template to prepare some novel peptides with improved stability and hydrophobicity. The antimicrobial activities exerted by these peptides against Gram positive and Gram negative bacteria were evaluated by MIC and CFU assays under physiological conditions. One peptide, AWRK6, was 2-4 fold more potent than Dy2, and was toxic to most of the bacterial strains tested, exhibiting a faster killing rate.  AWRK6 was most potent in alkaline environments, and this was related to the more highly organized secondary structure of the peptide, as revealed by circular dichroism spectroscopy. Furthermore, AWRK6 was more resistant than Dy2 to degradation by trypsin. The improved properties of AWRK6 suggested that the peptide could potentially be further developed into an antibiotic.</p><p> </p>

scholarly journals Add-On Therapy with Ertapenem in Infections with Multidrug Resistant Gram-Negative Bacteria: Pediatric Experience

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Sevgen Tanır Basaranoglu ◽  
Yasemin Ozsurekci ◽  
Kubra Aykac ◽  
Kamile Oktay Arıkan ◽  
Ayse Buyukcam ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Combination Treatment ◽  
Pediatric Patients ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
New Approach ◽  
Gram Negative ◽  
Optimal Therapy ◽  
Carbapenem Resistant

Optimal therapy for infections with carbapenem resistant GNB is not well established due to the weakness of data. Patients presenting with bloodstream infections caused by multidrug resistant Klebsiella pneumoniae were treated with a combination treatment. Optimal therapy for infections with carbapenem resistant Gram-negative bacteria is a serious problem in pediatric patients. We presented three cases who were successfully treated with addition of ertapenem to the combination treatment for bacteremia with multidrug resistant Klebsiella pneumoniae. Dual carbapenem treatment approach is a new approach for these infections and requires more data in children.

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