Effect of Titanium Dioxide Nanoparticles on the Expression of Efflux Pump and Quorum-Sensing Genes in MDR Pseudomonas aeruginosa Isolates

Abstract

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.

The impact of titanium oxide nanoparticles and low direct electric current on biofilm dispersal of $Bacillus~cereus$ and $Pseudomonas~aeruginosa$: A comparative study

“…This liberated, accelarated and oriented the charges/electron in the electrical field toward negatively charged EPS. In turn, this impaired the biofilm matrix stabilization, altered the surface charge, reduced hydrophobicity, perturbed bacterial membrane integrity, increased membrane permeability and increased ROS [56,57]. All these destructive effects were emphasized in Figs.…”

Self-Assembly and Disassembly of Glycol Chitosan/Photosensitizer Nano-Micelles for Antibacterial Photodynamic Therapy

“…However, these nanomaterials suffer from drug resistance development, 20−22 cytotoxicity, 3,6,8 complicated synthesis, 5,7,[11][12][13][14]17 or inefficient antibacterial efficacy. [8][9][10]16 For instance, metal and metal oxide nanoparticles (NPs) can cause cytotoxicity owing to oxidative stress, 23 while Si nanoparticles are prone to harm liver cells. 24 Besides, the resistance of microbes toward some of these nanomaterials was reported, such as Ag nanoparticles, Cu nanoparticles, and antimicrobial peptides.…”

“…The abuse of conventional antibiotics has resulted in a notable rise of multidrug-resistant (MDR) bacteria and antibiotic-resistant infections, severely threatening human health and making it urgent to develop new antibacterial strategies. , As a result, a vast array of nanomaterials based on Au, − Ag, ,, Cu, , TiO 2 , , Si, C, − peptides, , and polymers , have been developed. However, these nanomaterials suffer from drug resistance development, − cytotoxicity, ,, complicated synthesis, ,,− , or inefficient antibacterial efficacy. − , For instance, metal and metal oxide nanoparticles (NPs) can cause cytotoxicity owing to oxidative stress, while Si nanoparticles are prone to harm liver cells . Besides, the resistance of microbes toward some of these nanomaterials was reported, such as Ag nanoparticles, Cu nanoparticles, and antimicrobial peptides. − Therefore, it is still a long road to easily prepare effective antibacterial agents with high biosafety and no drug resistance.…”

Genomic Analysis of Antibiotics Resistance in Pathogens

“…This collection also gathers papers on antibiotic resistance of some of the major emerging infections pathogens such as Mycobacteroides abscessus [ 3 ], Klebsiella pneumoniae [ 4 , 5 ], Salmonella sp. [ 6 , 7 ], Francisella tularensis [ 8 ], Acinetobacter baumannii [ 9 , 10 ], or Pseudomonas aeruginosa [ 11 ] and other human pathogens such as Neisseria gonorrhoea [ 12 ], Staphylococcus aureus [ 13 ], or Escherichia coli [ 14 ]. Most of them are high-priority pathogens [ 15 ], according to the National Institute of Allergy and Infectious Diseases, and are globally and medically important pathogens.…”

“…Another Gamma Proteobacteria is Pseudomonas aeruginosa , which is an opportunistic human pathogen that is often difficult to treat with antibiotics due to its ability to form biofilms but also due to the expression of efflux pumps. Ahmed et al have studied the impact of titanium dioxide nanoparticles on the quorum-sensing genes controlling biofilm production and efflux pump gene expression [ 11 ].…”