Sub lethal levels of platinum nanoparticle cures plasmid and in combination with carbapenem, curtails carbapenem resistant Escherichia coli

Bharathan, Subhashree; Sundaramoorthy, Niranjana Sri; Chandrasekaran, Harini; Rangappa, Gagana; ArunKumar, GaneshPrasad; Subramaniyan, Siva Bala; Veerappan, Anbazhagan; Nagarajan, Saisubramanian

doi:10.1038/s41598-019-41489-3

Cited by 18 publications

(11 citation statements)

References 67 publications

(72 reference statements)

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“…was also confirmed in our recent studies [34]. Platinum nanoparticles have not been as extensively studied as silver nanoparticles but their anti-bacterial activity against Pseudomonas aeruginosa, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, Salmonella enteritidis, Candida albicans, and highly resistant Escherichia coli strains has already been described [35][36][37][38][39][40]. Moreover, recent studies have shown that PtNPs may inhibit biofilm formation by Salmonella typhi [41].…”

Section: Introductionsupporting

confidence: 68%

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

Hendiger¹,

Padzik

Sifaoui³

et al. 2020

Pathogens

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Free living, cosmopolitan amoebae from Acanthamoeba genus present a serious risk to human health. As facultative human parasites, these amoebae may cause Acanthamoeba keratitis (AK). Acanthamoeba keratitis is a severe, vision-threatening corneal infection with non-specific symptoms. The number of reported AK cases worldwide has been increasing every year. Moreover, 90% of Acanthamoeba keratitis cases are related to contact lens use. Wearing and storage contact lenses not in accordance with the physicians and manufacturers recommendations are the primary key risk factors of this disease. Amoebae can easily adhere to the contact lens surface and transmit to the corneal epithelium. Preventing amoebae adhesion to the contact lens surface could significantly decrease the number of AK infections. Until now, the effective therapy against AK is still under development. Currently proposed therapies are mainly limited to the chlorhexidine digluconate combined with propamidine isethionate or hexamidine applications, which are insufficient and very toxic to the eye. Due to lack of effective treatment, looking for new potential preventive agents is crucial to decrease the number of Acanthamoeba keratitis infections, especially among contact lens users. Nanoparticles have been already included in several novel therapies against bacteria, viruses, fungi, and protist. However, their anti-amoebic potential has not been fully tested yet. The aim of this study was to assess silver nanoparticles (AgNPs) and platinum nanoparticles (PtNPs) anti-amoebic activity and influence on the amoebae adhesion to the surface of four different groups of contact lenses—classified according to the Food and Drugs Administration (FDA) guidelines. The obtained results show that both tested nanoparticles were effective against Acanthamoeba trophozoites and decreased the amoebae adhesion to the contact lens surface. AgNPs showed better anti-amoebic activity to cytotoxicity dependence and reduced amoebae adhesion in a wider spectrum of the tested contact lenses. Our studies also confirmed that ionization next to hydration of the contact lens material is a crucial parameter influencing the Acanthamoeba adhesion to the contact lens surface. In conclusion, silver nanoparticles might be considered as a novel preventive agent against Acanthamoeba keratitis infection.

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Section: Introductionsupporting

confidence: 68%

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

Hendiger¹,

Padzik

Sifaoui³

et al. 2020

Pathogens

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“…Hence, there is an urgent need to search for alternative therapy to restore colistin sensitivity in colistin resistant Enterobacteriaceae . In our previous study 17 , we have shown that pectin capped platinum nanoparticles cures plasmid of the same strain (U3790) and restores sensitivity to meropenem in vitro and in vivo . In the present study, we used a combination of a MarR inhibitor and an appropriate efflux pump inhibitor to restore colistin sensitivity in the same strain.…”

Section: Discussionmentioning

confidence: 92%

“…Among the strains employed, an E. coli clinical isolate designated as U3790 (isolated from urine of infected child) was found to display resistance to a wide range of antimicrobials including colistin and hence became our strain of interest. In a previous study, we reported antimicrobial profiling of U3790 against diverse antimicrobial agents 17 . Hence, the antimicrobial effect of colistin, salicylate, and BC1 (benzochromene derivative) was evaluated against all strains employed in the present study (Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 99%

Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor

Sundaramoorthy

Suresh

Ganesan

et al. 2019

Sci Rep

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Antibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. in this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo. Antimicrobial resistance (AMR) poses a grave threat to public health and is attributed as the third major cause of mortality worldwide. Rise in infections caused by multidrug-resistant (MDR) pathogens prompted WHO to declare a list of 12 priority AMR pathogens in 2017, of which, carbapenem-resistant Enterobacteriaceae (Escherichia coli, Klebsiella spp, Serratia spp, Proteus spp) fall under critical priority group 1. Due to rising AMR menace, new antimicrobial agents or resistance modulatory agents to curtail AMR are urgently required. Recently, WHO has released its first report on AMR surveillance, which reveals an alarming trend of widespread dissemination of resistant traits among microbes globally, wherein resistance to commonly used antibiotics were found to range from 0-82% 2. Carbapenem-resistant Enterobacteriaceae (CREB) is becoming resistant to almost all antibiotics and its clinical outcomes are also poor 3,4. Among Enterobacteriaceae, Escherichia coli tops the list in causing a wide range of clinical infections due to their high prevalence, multidrug resistance and most importantly, rapid acquisition/ transfer of resistance traits by horizontal gene transfer 5,6. Colistin is a drug of last resort for CREBs 7. Colistin resistance implies a pan drug resistant state, with...

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“…Such information is vital if we are to judge accurately whether the pathogen detected by UTI-HMGS represents an active infection that requires intervention. The plasmid-mediated transfer of resistance genes among bacterial species is recognized as one of the most important mechanisms that can accelerate the dissemination and emergence of drug resistance (Bai et al, 2017;Bharathan et al, 2019) via the b-lactamase gene, the carbapenem resistance gene, VRE, and MRSA drug resistance (Lin and Hayden, 2010;Sultan et al, 2018;Salah et al, 2019;van Beek et al, 2019). These factors increase the frequency of resistant strains and increase the threat for modern medicine.…”

Section: Discussionmentioning

confidence: 99%

The Direct Semi-Quantitative Detection of 18 Pathogens and Simultaneous Screening for Nine Resistance Genes in Clinical Urine Samples by a High-Throughput Multiplex Genetic Detection System

Sun

Liu

Zhang

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundUrinary tract infections (UTIs) are one the most common infections. The rapid and accurate identification of uropathogens, and the determination of antimicrobial susceptibility, are essential aspects of the management of UTIs. However, existing detection methods are associated with certain limitations. In this study, a new urinary tract infection high-throughput multiplex genetic detection system (UTI-HMGS) was developed for the semi-quantitative detection of 18 pathogens and the simultaneously screening of nine resistance genes directly from the clinical urine sample within 4 hours.MethodsWe designed and optimized a multiplex polymerase chain reaction (PCR) involving fluorescent dye-labeled specific primers to detect 18 pathogens and nine resistance genes. The specificity of the UTI-HMGS was tested using standard strains or plasmids for each gene target. The sensitivity of the UTI-HMGS assay was tested by the detection of serial tenfold dilutions of plasmids or simulated positive urine samples. We also collected clinical urine samples and used these to perform urine culture and antimicrobial susceptibility testing (AST). Finally, all urine samples were detected by UTI-HMGS and the results were compared with both urine culture and Sanger sequencing.ResultsUTI-HMGS showed high levels of sensitivity and specificity for the detection of uropathogens when compared with culture and sequencing. In addition, ten species of bacteria and three species of fungi were detected semi-quantitatively to allow accurate discrimination of significant bacteriuria and candiduria. The sensitivity of the UTI-HMGS for the all the target genes could reach 50 copies per reaction. In total, 531 urine samples were collected and analyzed by UTI-HMGS, which exhibited high levels of sensitivity and specificity for the detection of uropathogens and resistance genes when compared with Sanger sequencing. The results from UTI-HMGS showed that the detection rates of 15 pathogens were significantly higher (P<0.05) than that of the culture method. In addition, there were 41(7.72%, 41/531) urine samples were positive for difficult-to-culture pathogens, which were missed detected by routine culture method.ConclusionsUTI-HMGS proved to be an efficient method for the direct semi-quantitative detection of 18 uropathogens and the simultaneously screening of nine antibiotic resistance genes in urine samples. The UTI-HMGS could represent an alternative method for the clinical detection and monitoring of antibiotic resistance.

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Sub lethal levels of platinum nanoparticle cures plasmid and in combination with carbapenem, curtails carbapenem resistant Escherichia coli

Cited by 18 publications

References 67 publications

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

Silver Nanoparticles as a Novel Potential Preventive Agent against Acanthamoeba Keratitis

Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor

The Direct Semi-Quantitative Detection of 18 Pathogens and Simultaneous Screening for Nine Resistance Genes in Clinical Urine Samples by a High-Throughput Multiplex Genetic Detection System

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