Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance

Abstract

Background 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. 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. Results NAg 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. Conclusion The 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

Benefits of Usage of Immobilized Silver Nanoparticles as Pseudomonas aeruginosa Antibiofilm Factors

“…Singh et al [ 35 ] used AgNPs with a size of 20–40 nm and noted that the MIC value was 6.25 μg/mL against the P. aeruginosa strain. Mann et al [ 36 ] showed that the MIC value of AgNPs against P. aeruginosa was only 3 μg/mL when the size of these nanoparticles was 2 nm.…”

Drug Resistance Reversal Potential of Nanoparticles/Nanocomposites via Antibiotic’s Potentiation in Multi Drug Resistant P. aeruginosa

“…Biofilms are the extracellular matrix that is responsible for the protection of cells from different stresses, including antibiotic stress [ 15 , 29 , 39 , 44 ]. Biofilm-producing microbes have also been known for their resistance to a range of antimicrobial agents, including clinically relevant antibiotics [ 15 , 29 , 39 , 44 , 47 ]. Overexpressed efflux pump mechanism is evident from the luxuriant growth on the high concentration of Et-Br, which is evident by a higher level of fluorescence under the UV-transilluminator.…”

“…Overexpressed efflux pump mechanism is evident from the luxuriant growth on the high concentration of Et-Br, which is evident by a higher level of fluorescence under the UV-transilluminator. Efflux pumps are supposed to be the key component that plays a crucial role in resistance [ 15 , 29 , 47 ]. However, in this study, the clinical isolate PS-2 was found to be highly resistant due to the coordination of MBL, efflux pump, and biofilm.…”

“…For any isolate which shows luxuriant growth on the higher concentration of Et-Br, it is supposed that their resistance mechanism is mediated by an efflux pump and production of metallo-β-lactamase makes them be considered as superbugs [ 5 , 14 , 17 , 39 , 40 , 41 , 48 , 49 , 50 ]. The critical superbug P. aeruginosa exploits efflux pump, biofilm, and MBL to achieve a high degree of resistance [ 5 , 14 , 45 , 47 , 50 , 51 , 52 ].…”

“…In this study, all the used nanomaterials (GO, GO/ZnO, GO–CS, GO–CS/ZnO, and ZnO) were also able to inhibit the biofilm formation. Several reports indicated that nanomaterials were reported to inhibit biofilm formation [ 47 , 56 , 60 , 61 , 62 , 63 ]. Resistance towards ethidium bromide (Et-Br) is considered a marker of MDR mediated by over expression of efflux pumps [ 6 , 48 , 49 , 50 , 51 , 61 , 62 , 64 , 65 ].…”