Abstract

BackgroundTreatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth.ResultsNAg could inhibit the formation as well as eradicating an already grown biofilm of Pseudomonas aeruginosa, a pathogen notorious for its resilience to antibiotics. The biofilm-forming bacterium however, evolved a reduced sensitivity to the nanoparticle. Evidence suggests that survival is linked to the development of persister cells within the population. A similar adaptation was also seen upon prolonged exposures to ionic silver (Ag+). The persister population resumed normal growth after subsequent passage in the absence of silver, highlighting the potential risks of recurrent infections with long-term NAg (and Ag+) treatments of biofilm growth. The present study further observed a potential silver/antibiotic cross-resistance, whereby NAg (as well as Ag+) could not eradicate an already growing gentamicin-resistant P. aeruginosa biofilm. The phenomena is thought to result from the hindered biofilm penetration of the silver species. In contrast, both silver formulations inhibited biofilm formation of the resistant strain, presenting a promising avenue for the control of biofilm-forming antibiotic-resistant bacteria.ConclusionThe findings signify the importance to study the nanoparticle adaptation phenomena in the biofilm mode of bacterial growth, which are apparently unique to those already reported with the planktonic growth counterparts. This work sets the foundation for future studies in other globally significant bacterial pathogens when present as biofilms. Scientifically based strategies for management of pathogenic growth is necessary, particularly in this era of increasing antibiotic resistance.Graphic abstract

Highlights

  • Treatment of bacterial biofilms are difficult and in many cases, expensive

  • In summary, the work reported unique silver adaptation mechanisms with pathogenic biofilm-forming bacterium that have not been previously reported with planktonic bacterium studies

  • While silver nanoparticles (NAg) and ionic silver ­(Ag+) are effective in inhibiting and eradicating P. aeruginosa biofilm growth, we found evidence of persister cells as a mechanism of survival upon repeated NAg and A­ g+ exposures

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Summary

Introduction

Treatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. Treatment of biofilm-related infections is a challenge Unlike their planktonic counterparts, bacteria in biofilms are protected in a self-produced polymeric matrix, referred to as extracellular polymeric substance (EPS), rendering them resilient to antibiotics (Fig. 1A) [1]. Bacteria in biofilms can transfer antibiotic resistance genes to each other and at higher frequencies than their planktonic counterparts; with studies, for instance, reporting the transfer of ESBL genes-harbouring plasmids (the genes encode extendedspectrum β-lactamase enzymes that confer resistance to β-lactam antibiotics) in Klebsiella pneumoniae biofilm [8]. These mechanisms help to protect biofilm cells from antibiotics and other stressors. This has prompted research on non-antibiotic therapy options for biofilm growth inhibition and eradication, with one of the major alternatives being the development of the broad spectrum antibacterial nanoparticles, nanosilver (NAg) [9]

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