Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies

Silver nanoparticles (AgNPs) have been one of the most attractive nanomaterials in biomedicine due to their unique physicochemical properties. In this paper, we review the state-of-the-art advances of AgNPs in the synthesis methods, medical applications and biosafety of AgNPs. The synthesis methods of AgNPs include physical, chemical and biological routes. AgNPs are mainly used for antimicrobial and anticancer therapy, and also applied in the promotion of wound repair and bone healing, or as the vaccine adjuvant, anti-diabetic agent and biosensors. This review also summarizes the biological action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure. Despite these therapeutic benefits, their biological safety problems such as potential toxicity on cells, tissue, and organs should be paid enough attention. Besides, we briefly introduce a new type of Ag particles smaller than AgNPs, silver Angstrom (A, 1 A = 0.1 nm) particles (AgAPs), which exhibit better biological activity and lower toxicity compared with AgNPs. Finally, we conclude the current challenges and point out the future development direction of AgNPs.

Silver nanoparticles: Synthesis, medical applications and biosafety

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.

/pdf/nano-strategies-to-fight-multidrug-resistant-bacteria-a-31jw0w0kam.pdf

Nano-Strategies to Fight Multidrug Resistant Bacteria-"A Battle of the Titans".

Pseudomonas aeruginosa is an opportunistic human pathogen causing devastating acute and chronic infections in individuals with compromised immune systems. Its highly notorious persistence in clinical settings is attributed to its ability to form antibiotic-resistant biofilms. Biofilm is an architecture built mostly by autogenic extracellular polymeric substances which function as a scaffold to encase the bacteria together on surfaces, and to protect them from environmental stresses, impedes phagocytosis and thereby conferring the capacity for colonization and long-term persistence. Here we review the current knowledge on P. aeruginosa biofilms, its development stages, and molecular mechanisms of invasion and persistence conferred by biofilms. Explosive cell lysis within bacterial biofilm to produce essential communal materials, and interspecies biofilms of P. aeruginosa and commensal Streptococcus which impedes P. aeruginosa virulence and possibly improves disease conditions will also be discussed. Recent research on diagnostics of P. aeruginosa infections will be investigated. Finally, therapeutic strategies for the treatment of P. aeruginosa biofilms along with their advantages and limitations will be compiled.

https://www.mdpi.com/1422-0067/21/22/8671/pdf

Pseudomonas aeruginosa Biofilms

Metal‐Based Nanomaterials in Biomedical Applications: Antimicrobial Activity and Cytotoxicity Aspects

Pseudomonas aeruginosa has great intrinsic antimicrobial resistance limiting the number of effective antibiotics. Thus, other antimicrobial agents such as silver nanoparticles (AgNPs) are considered potential agents to help manage and prevent infections. AgNPs can be used in several applications against bacteria resistant to common antibiotics or even multi-resistant bacteria such as P. aeruginosa. This study assessed the antimicrobial activity of commercial 10 nm AgNPs on two hospital strains of P. aeruginosa resistant to a large number of antibiotics and a reference strain from a culture collection. All strains were susceptible to 5 µg/mL nanoparticles solution. Reference strains INCQS 0230 and P.a.1 were sensitive to AgNPs at concentrations of 1.25 and 0.156 µg/mL, respectively; however, this was not observed for hospital strain P.a.2, which was more resistant to all antibiotics and AgNPs tested. Cytotoxicity evaluation indicated that AgNPs, up to a concentration of 2.5 µg/mL, are very safe for all cell lines tested. At 5.0 µg/mL, AgNPs had a discrete cytotoxic effect on tumor cells HeLa and HepG2. Results showed the potential of using AgNPs as an alternative to conventional antimicrobial agents that are currently used, and a perspective for application of nanosilver with antibiotics to enhance antimicrobial activity.

/pdf/antibacterial-effect-of-silver-nanoparticles-in-pseudomonas-2885q3nvb0.pdf

Antibacterial effect of silver nanoparticles in Pseudomonas aeruginosa.

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Antibacterial effect of silver nanoparticles in Pseudomonas aeruginosa.