scholarly journals Synergistic Interaction between Silver Nanoparticles and Membrane-Permeabilizing Antimicrobial Peptides

2009 ◽  
Vol 53 (8) ◽  
pp. 3538-3540 ◽  
Author(s):  
Serge Ruden ◽  
Kai Hilpert ◽  
Marina Berditsch ◽  
Parvesh Wadhwani ◽  
Anne S. Ulrich

ABSTRACT Silver nanoparticles, as well as antimicrobial peptides (AMPs), can be used to fight infectious diseases. Since AMPs are known to permeabilize bacterial membranes and might therefore help silver nanoparticles to access internal target sites, we investigated their combined activities and showed synergistic effects between polymyxin B and silver nanoparticles for gram-negative bacteria.

2006 ◽  
Vol 50 (7) ◽  
pp. 2361-2367 ◽  
Author(s):  
Miguel A. Campos ◽  
Pau Morey ◽  
José A. Bengoechea

ABSTRACT The treatment of infections caused by bacteria resistant to the vast majority of antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the front line of defense in those areas exposed to microorganisms, and there is intensive research to explore their use as new antibacterial agents. On the other hand, it is known that subinhibitory concentrations of antibiotics affect the expression of numerous bacterial traits. In this work we evaluated whether treatment of bacteria with subinhibitory concentrations of quinolones may alter the sensitivity to APs. A 1-h treatment of Klebsiella pneumoniae with 0.25× the MIC of ciprofloxacin rendered bacteria more sensitive to polymyxins B and E, human neutrophil defensin 1, and β-defensin 1. Levofloxacin and nalidixic acid at 0.25× the MICs also increased the sensitivity of K. pneumoniae to polymyxin B, whereas gentamicin and ceftazidime at 0.25× the MICs did not have such an effect. Ciprofloxacin also increased the sensitivities of K. pneumoniae ciprofloxacin-resistant strains to polymyxin B. Two other pathogens, Pseudomonas aeruginosa and Haemophilus influenzae, also became more sensitive to polymyxins B and E after treatment with 0.25× the MIC of ciprofloxacin. Incubation with ciprofloxacin did not alter the expression of the K. pneumoniae loci involved in resistance to APs. A 1-N-phenyl-naphthylamine assay showed that ciprofloxacin and levofloxacin increased the permeabilities of the K. pneumoniae and P. aeruginosa outer membranes, while divalent cations antagonized this action. Finally, we demonstrated that ciprofloxacin and levofloxacin increased the binding of APs to the outer membrane by using dansylated polymyxin B.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tessa B. Moyer ◽  
Ashleigh L. Purvis ◽  
Andrew J. Wommack ◽  
Leslie M. Hicks

Abstract Background Plant defensins are a broadly distributed family of antimicrobial peptides which have been primarily studied for agriculturally relevant antifungal activity. Recent studies have probed defensins against Gram-negative bacteria revealing evidence for multiple mechanisms of action including membrane lysis and ribosomal inhibition. Herein, a truncated synthetic analog containing the γ-core motif of Amaranthus tricolor DEF2 (Atr-DEF2) reveals Gram-negative antibacterial activity and its mechanism of action is probed via proteomics, outer membrane permeability studies, and iron reduction/chelation assays. Results Atr-DEF2(G39-C54) demonstrated activity against two Gram-negative human bacterial pathogens, Escherichia coli and Klebsiella pneumoniae. Quantitative proteomics revealed changes in the E. coli proteome in response to treatment of sub-lethal concentrations of the truncated defensin, including bacterial outer membrane (OM) and iron acquisition/processing related proteins. Modification of OM charge is a common response of Gram-negative bacteria to membrane lytic antimicrobial peptides (AMPs) to reduce electrostatic interactions, and this mechanism of action was confirmed for Atr-DEF2(G39-C54) via an N-phenylnaphthalen-1-amine uptake assay. Additionally, in vitro assays confirmed the capacity of Atr-DEF2(G39-C54) to reduce Fe3+ and chelate Fe2+ at cell culture relevant concentrations, thus limiting the availability of essential enzymatic cofactors. Conclusions This study highlights the utility of plant defensin γ-core motif synthetic analogs for characterization of novel defensin activity. Proteomic changes in E. coli after treatment with Atr-DEF2(G39-C54) supported the hypothesis that membrane lysis is an important component of γ-core motif mediated antibacterial activity but also emphasized that other properties, such as metal sequestration, may contribute to a multifaceted mechanism of action.


2003 ◽  
Vol 47 (8) ◽  
pp. 2659-2662 ◽  
Author(s):  
John P. Ouderkirk ◽  
Jill A. Nord ◽  
Glenn S. Turett ◽  
Jay Ward Kislak

ABSTRACT Reported rates of nephrotoxicity associated with the systemic use of polymyxins have varied widely. The emergence of infections due to multiresistant gram-negative bacteria has necessitated the use of systemic polymyxin B once again for the treatment of such infections. We retrospectively investigated the rate of nephrotoxicity in patients receiving polymyxin B parenterally for the treatment of infections caused by multiresistant gram-negative bacteria from October 1999 to September 2000. Demographic and clinical information was obtained for 60 patients. Outcome measures of interest were renal toxicity and clinical and microbiologic efficacy. Renal failure developed in 14% of the patients, all of whom had normal baseline renal function. Development of renal failure was independent of the daily and cumulative doses of polymyxin B and the length of treatment but was significantly associated with older age (76 versus 59 years, P = 0.02). The overall mortality was 20%, but it increased to 57% in those who developed renal failure. The organism was cleared in 88% of the patients from whom repeat specimens were obtained. The use of polymyxin B to treat multiresistant gram-negative infections was highly effective and associated with a lower rate of nephrotoxicity than previously described.


Chemistry ◽  
2021 ◽  
Vol 3 (4) ◽  
pp. 1271-1285
Author(s):  
Patricia Zimet ◽  
Ruby Valadez ◽  
Sofía Raffaelli ◽  
María Belén Estevez ◽  
Helena Pardo ◽  
...  

Microbial technology offers a green alternative for the synthesis of value-added nanomaterials. In particular, fungal compounds can improve silver nanoparticle production, stabilizing colloidal nanoparticles. Based on a previous study by our group, silver nanoparticles obtained using the extracellular cell-free extracts of Phanerochaete chrysosporium (PchNPs) have shown antimicrobial and antibiofilm activity against Gram-negative bacteria. Moreover, nisin—a bacteriocin widely used as a natural food preservative—has recently gained much attention due its antimicrobial action against Gram-positive bacteria in biomedical applications. Therefore, the aim of this work was to conjugate biogenic silver nanoparticles (PchNPs) with nisin to obtain nanoconjugates (PchNPs@nis) with enhanced antimicrobial properties. Characterization assays were conducted to determine physicochemical properties of PchNPs@nis, and also their antibacterial and antibiofilm activities were studied. The formation of PchNPs@nis was confirmed by UV-Vis, TEM, and Raman spectroscopy analysis. Different PchNPs@nis nanobioconjugates showed diameter values in the range of 60–130 nm by DLS and surface charge values between −20 and −13 mV. Nisin showed an excellent affinity to PchNPs, with binding efficiencies higher than 75%. Stable synthesized PchNPs@nis nanobioconjugates were not only able to inhibit biofilm formation by S. aureus, but also showed inhibition of the planktonic cell growth of Staphyloccocus aureus and Escherichia coli, broadening the spectrum of action of the unconjugated antimicrobials against Gram-positive and Gram-negative bacteria. In conclusion, these results show the promising application of PchNPs@nis, prepared via green technology, as potential antimicrobial nanomaterials.


Author(s):  
L.V. Kataeva ◽  
A.P. Rebeshchenko ◽  
T.F. Stepanova ◽  
O.V. Posoiuznykh ◽  
Le Thanh Hai ◽  
...  

We studied the microflora structure and resistance gathered from the biomaterial of patients and the environment objects of various departments at the National hospital of Pediatrics in Hanoi. 140 clinical samples of biomaterials from 74 patients treated in the intensive care unit, the infectious diseases and the gastroenterology departments were studied. A systematic approach including microbiological, epidemiological and statistical research methods was used in carrying out the study. Bacteria of the Enterobacteriaceae family (38.5 per cent) prevailed in the biomaterial of intensive care unit patients. Nonfermentative Gram-negative bacteria (46.5 per cent) occupied the leading positions in the infectious diseases department and Gram-positive bacteria (39.3 per cent) were in the gastroenterology department. Gram-positive flora (60.2 per cent in the intensive care unit and 50.7 per cent in the infectious diseases department) prevailed in the microflora structure gathered from hospital environment objects. We identified the prevalence of bacteria of the genus Enterobacteriaceae and non-fermentative Gram-negative bacteria with a wide spectrum of resistance in the departments of the National Hospital of Pediatrics.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostálová ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ni Zhang ◽  
Lichong Zhu ◽  
Qiuhong Ouyang ◽  
Saisai Yue ◽  
Yichun Huang ◽  
...  

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.


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