Polymeric Composites with Silver (I) Cyanoximates Inhibit Biofilm Formation of Gram-Positive and Gram-Negative Bacteria.

S R Lotlikar,M Guragain,S Hamilton,M A Patrauchan,T Grant,R Rogers,S Popis,M Whited,E Gallaway,N G Gerasimchuk

doi:10.3390/polym11061018

S R Lotlikar, M Guragain + Show 8 more

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https://doi.org/10.3390/polym11061018

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Journal: Polymers	Publication Date: Jun 9, 2019
Citations: 11	License type: CC BY 4.0

Affiliation: Oklahoma State University, Missouri State University

Abstract

Biofilms are surface-associated microbial communities known for their increased resistance to antimicrobials and host factors. This resistance introduces a critical clinical challenge, particularly in cases associated with implants increasing the predisposition for bacterial infections. Preventing such infections requires the development of novel antimicrobials or compounds that enhance bactericidal effect of currently available antibiotics. We have synthesized and characterized twelve novel silver(I) cyanoximates designated as Ag(ACO), Ag(BCO), Ag(CCO), Ag(ECO), Ag(PiCO), Ag(PICO) (yellow and red polymorphs), Ag(BIHCO), Ag(BIMCO), Ag(BOCO), Ag(BTCO), Ag(MCO) and Ag(PiPCO). The compounds exhibit a remarkable resistance to high intensity visible light, UV radiation and heat and have poor solubility in water. All these compounds can be well incorporated into the light-curable acrylate polymeric composites that are currently used as dental fillers or adhesives of indwelling medical devices. A range of dry weight % from 0.5 to 5.0 of the compounds was tested in this study. To study the potential of these compounds in preventing planktonic and biofilm growth of bacteria, we selected two human pathogens (Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus) and Gram-positive environmental isolate Bacillus aryabhattai. Both planktonic and biofilm growth was abolished completely in the presence of 0.5% to 5% of the compounds. The most efficient inhibition was shown by Ag(PiCO), Ag(BIHCO) and Ag(BTCO). The inhibition of biofilm growth by Ag(PiCO)-yellow was confirmed by scanning electron microscopy (SEM). Application of Ag(BTCO) and Ag(PiCO)-red in combination with tobramycin, the antibiotic commonly used to treat P. aeruginosa infections, showed a significant synergistic effect. Finally, the inhibitory effect lasted for at least 120 h in P. aeruginosa and 36 h in S. aureus and B. aryabhattai. Overall, several silver(I) cyanoximates complexes efficiently prevent biofilm development of both Gram-negative and Gram-positive bacteria and present a particularly significant potential for applications against P. aeruginosa infections.

Highlights

Healthcare-associated infections are becoming increasingly prevalent in the United States.According to the 2014 report from the Center for Disease and Prevention (CDC), the estimated burden of nosocomial infections was 722,000 cases leading to about 75,000 fatalities
The cyanoximes used in this study (Scheme 1) were obtained in 2–5 g quantities according to reported procedures [43]
Twelve solid pure Ag(I) cyanoximates of AgL composition were obtained in 83–98% yield (Tables S3 and S4)

Summary

Introduction

Healthcare-associated infections are becoming increasingly prevalent in the United States.According to the 2014 report from the Center for Disease and Prevention (CDC), the estimated burden of nosocomial infections was 722,000 cases leading to about 75,000 fatalities. Healthcare-associated infections are becoming increasingly prevalent in the United States. A significant number of such infections are commonly associated with implanting surgical devices. These infections are increasingly difficult to treat due to continuously growing prevalence of antibiotic resistant bacteria in hospital settings and lead to considerable morbidity and healthcare costs [1]. Pathogenic bacteria usually enter the surgical site during operative procedures or infect the wounds post-surgically [2]. Such surgical implant infections are caused by diverse species of bacteria, including species of Staphylococcus, Streptococcus and Pseudomonas genera [3]. P. aeruginosa represents a particular challenge due its antibiotic resistance (reviewed in Reference [6]) and ability to colonize and form biofilms on diverse surfaces, including those of devices, such as cardiac pacemakers, defibrillators and prosthetic cardiac valves [7]

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