scholarly journals Vancomycin-Lipopeptide Conjugates with High Antimicrobial Activity on Vancomycin-Resistant Enterococci

2020 ◽  
Vol 13 (6) ◽  
pp. 110 ◽  
Author(s):  
Eric Mühlberg ◽  
Florian Umstätter ◽  
Cornelius Domhan ◽  
Tobias Hertlein ◽  
Knut Ohlsen ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Fatty Acid ◽  
Chain Length ◽  
Structural Modification ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, there are only a few compounds capable of serving as a last resort for severe infections. Therefore, approaches to control multidrug-resistant bacteria must be implemented. Here, a strategy of reactivating the established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation to overcome the resistance of multidrug-resistant bacteria was followed. This study especially focuses on the structure–activity relationship, depending on the modification site and fatty acid chain length. The synthesized conjugates showed high antimicrobial potential on vancomycin-resistant enterococci. We were able to demonstrate that the antimicrobial activity of the vancomycin-lipopeptide conjugates depends on the chain length of the attached fatty acid. All conjugates showed good cytocompatibility in vitro and in vivo. Radiolabeling enabled the in vivo determination of pharmacokinetics in Wistar rats by molecular imaging and biodistribution studies. An improved biodistribution profile in comparison to unmodified vancomycin was observed. While vancomycin is rapidly excreted by the kidneys, the most potent conjugate shows a hepatobiliary excretion profile. In conclusion, these results demonstrate the potential of the structural modification of already established antibiotics to provide highly active compounds for tackling multidrug-resistant bacteria.

scholarly journals High Colonization Rate and Heterogeneity of ESBL- and Carbapenemase-Producing Enterobacteriaceae Isolated from Gull Feces in Lisbon, Portugal

2020 ◽  
Vol 8 (10) ◽  
pp. 1487
Author(s):  
Marta Aires-de-Sousa ◽  
Claudine Fournier ◽  
Elizeth Lopes ◽  
Hermínia de Lencastre ◽  
Patrice Nordmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Bacterial Species ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Encoding Genes

In order to evaluate whether seagulls living on the Lisbon coastline, Portugal, might be colonized and consequently represent potential spreaders of multidrug-resistant bacteria, a total of 88 gull fecal samples were screened for detection of extended-spectrum β-lactamase (ESBL)- or carbapenemase-producing Enterobacteriaceae for methicillin-resistant Staphylococcus aureus (MRSA) and for vancomycin-resistant Enterococci (VRE). A large proportion of samples yielded carbapenemase- or ESBL-producing Enterobacteriaceae (16% and 55%, respectively), while only two MRSA and two VRE were detected. Mating-out assays followed by PCR and whole-plasmid sequencing allowed to identify carbapenemase and ESBL encoding genes. Among 24 carbapenemase-producing isolates, there were mainly Klebsiella pneumoniae (50%) and Escherichia coli (33%). OXA-181 was the most common carbapenemase identified (54%), followed by OXA-48 (25%) and KPC-2 (17%). Ten different ESBLs were found among 62 ESBL-producing isolates, mainly being CTX-M-type enzymes (87%). Co-occurrence in single samples of multiple ESBL- and carbapenemase producers belonging to different bacterial species was observed in some cases. Seagulls constitute an important source for spreading multidrug-resistant bacteria in the environment and their gut microbiota a formidable microenvironment for transfer of resistance genes within bacterial species.

Renaissance of vancomycin: approaches for breaking antibiotic resistance in multidrug-resistant bacteria

2020 ◽  
Vol 66 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Eric Mühlberg ◽  
Florian Umstätter ◽  
Christian Kleist ◽  
Cornelius Domhan ◽  
Walter Mier ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Structural Modifications ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
New Antibiotics ◽  
Life Threatening ◽  
Severe Infections ◽  
Vancomycin Resistant

The emergence of multidrug-resistant bacteria demands innovations in the development of new antibiotics. For decades, the glycopeptide antibiotic vancomycin has been considered as the “last resort” treatment of severe infections caused by Gram-positive bacteria. Since the discovery of the first vancomycin-resistant enterococci strains in the late 1980s, the number of resistances has been steadily rising, with often life-threatening consequences. As an alternative to the generation of completely new substances, novel approaches focus on structural modifications of established antibiotics such as vancomycin to overcome these resistances. Here, we provide an overview of several promising modifications of vancomycin to restore its efficacy against vancomycin-resistant enterococci.

Antimicrobial activity and biofilm inhibition of riparins I, II and III and ultrastructural changes in multidrug-resistant bacteria of medical importance

2020 ◽  
Vol 149 ◽  
pp. 104529
Author(s):  
Jorge Belém Oliveira-Júnior ◽  
Everton Morais da Silva ◽  
Dyana Leal Veras ◽  
Karla Raíza Cardoso Ribeiro ◽  
Catarina Fernandes de Freitas ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Multidrug Resistant ◽  
Ultrastructural Changes ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Biofilm Inhibition ◽  
Medical Importance

scholarly journals Antimicrobial activity of surfactants produced by Bacillus subtilis R14 against multidrug-resistant bacteria

2007 ◽  
Vol 38 (4) ◽  
pp. 704-709 ◽  
Author(s):  
Paulo André Vicente Fernandes ◽  
Isabel Renata de Arruda ◽  
Antônio Fernando Amatto Botelho dos Santos ◽  
Ana Albertina de Araújo ◽  
Ana Maria Souto Maior ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Bacillus Subtilis ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria

scholarly journals New Antimicrobial Bioactivity against Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 665
Author(s):  
Iliana E Escobar ◽  
Alexis White ◽  
Wooseong Kim ◽  
Eleftherios Mylonakis
Keyword(s):  
Staphylococcus Aureus ◽  
Kinase Inhibitor ◽  
Cell Attachment ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
C Elegans ◽  
Vancomycin Resistant ◽  
High Concentrations

Multidrug-resistant pathogens pose a serious threat to human health. For decades, the antibiotic vancomycin has been a potent option when treating Gram-positive multidrug-resistant infections. Nonetheless, in recent decades, we have begun to see an increase in vancomycin-resistant bacteria. Here, we show that the nuclear factor-kappa B (NF-κB) inhibitor N-[3,5-Bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (IMD0354) was identified as a positive hit through a Caenorhabditis elegans–methicillin-resistant Staphylococcus aureus (MRSA) infection screen. IMD0354 was a potent bacteriostatic drug capable of working at a minimal inhibitory concentration (MIC) as low as 0.06 µg/mL against various vancomycin-resistant strains. Interestingly, IMD0354 showed no hemolytic activity at concentrations as high as 16 µg/mL and is minimally toxic to C. elegans in vivo with 90% survival up to 64 µg/mL. In addition, we demonstrated that IMD0354′s mechanism of action at high concentrations is membrane permeabilization. Lastly, we found that IMD0354 is able to inhibit vancomycin-resistant Staphylococcus aureus (VRSA) initial cell attachment and biofilm formation at sub-MIC levels and above. Our work highlights that the NF-κB inhibitor IMD0354 has promising potential as a lead compound and an antimicrobial therapeutic candidate capable of combating multidrug-resistant bacteria.

scholarly journals The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Amy B. Howell ◽  
Doris H. D'Souza
Keyword(s):  
Antimicrobial Activity ◽  
Foodborne Pathogens ◽  
Clinical Results ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Oral Bacteria ◽  
Resistant Bacteria ◽  
Wide Range

Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates’ antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes fromin vitrocell-based assays, necessitating further confirmation ofin vivoefficacy through human clinical trials.

scholarly journals Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 501 ◽  
Author(s):  
Berthony Deslouches ◽  
Ronald C. Montelaro ◽  
Ken L. Urish ◽  
Yuanpu P. Di
Keyword(s):  
Antimicrobial Peptides ◽  
De Novo ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
Health Crisis ◽  
Test Conditions ◽  
Reduced Activity

The increasing rate of antibiotic resistance constitutes a global health crisis. Antimicrobial peptides (AMPs) have the property to selectively kill bacteria regardless of resistance to traditional antibiotics. However, several challenges (e.g., reduced activity in the presence of serum and lack of efficacy in vivo) to clinical development need to be overcome. In the last two decades, we have addressed many of those challenges by engineering cationic AMPs de novo for optimization under test conditions that typically inhibit the activities of natural AMPs, including systemic efficacy. We reviewed some of the most promising data of the last two decades in the context of the advancement of the field of helical AMPs toward clinical development.

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