Vancomycin and nisin-modified magnetic Fe3O4@SiO2 nanostructures coated with chitosan to enhance antibacterial efficiency against methicillin resistant Staphylococcus aureus (MRSA) infection in a murine superficial wound model.

BACKGROUND: The objective of this research was to prepare some Fe3O4@SiO2@Chitosan (CS) magnetic nanocomposites coupled with nisin, and vancomycin to evaluate their antibacterial efficacy under both in vitro and in vivo against the methicillin-resistant Staphylococcus. aureus (MRSA). METHODS: In this survey, the Fe3O4@SiO2 magnetic nanoparticles (MNPs) were constructed as a core and covered the surface of MNPs via crosslinking CS by glutaraldehyde as a shell, then functionalized with vancomycin and nisin to enhance the inhibitory effects of nanoparticles (NPs). X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscope (FE-SEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS) techniques were then used to describe the nanostructures. RESULTS: Based on the XRD, and FE-SEM findings, the average size of the modified magnetic nanomaterials were estimated to be around 22-35 nm, and 34-47 nm, respectively. The vancomycin was conjugated in three polymer-drug ratios; 1:1, 2:1 and 3:1, with the percentages of 45.52%, 35.68%, and 24.4%, respectively. The polymer/drug ratio of 1:1 exhibited the slowest release rate of vancomycin from the Fe3O4@SiO2@CS-VANCO nanocomposites during 24 h, which was selected to examine their antimicrobial effects under in vivo conditions. The nisin was grafted onto the nanocomposites at around 73.2-87.2%. All the compounds resulted in a marked reduction in the bacterial burden (P-value < 0.05). CONCLUSION: The vancomycin-functionalized nanocomposites exhibited to be more efficient in eradicating the bacterial cells both in vitro and in vivo. These findings introduce a novel bacteriocin-metallic nanocomposite that can suppress the normal bacterial function on demand for the treatment of MRSA skin infections.

A Comprehensive Study of the Relationship between the Production of ß-Lactamase Enzymes and Iron/Siderophore Uptake Regulatory Genes in Clinical Isolates of Acinetobacter baumannii.

BACKGROUND: The iron/siderophore uptake system (IUS) involved in the Acinetobacter baumannii pathogenicity. However, IUS's role in antibiotic resistance and the production of ß-lactamase enzymes of A. baumannii are unclear. This study aimed to investigate the relationship between the production of ß-lactamase enzymes and IUS regulatory genes in clinical isolates of A. baumannii. Methods. A. baumannii isolates were collected from clinical isolates using biochemical tests. The antibiotic resistance patterns and ß-lactamase-producing strains were identified using the disk diffusion method (DDM). Also, IUS genes were detected by the polymerase chain reaction (PCR) method. RESULTS: Seventy-two (72) A. baumannii isolates were collected from a different clinical specimen. Gentamicin-resistant strains (43%) had the highest frequency, and aztreonam-resistant strains (12.5%) had the lowest frequency. Also, the distribution of AmpC and MBL producing isolates were 27.7% and 35%, respectively. Moreover, the frequencies of basD, bauA, pld, paaE, entA, feoB, hemO, and tonB genes were as follows: 12.5%, 15.2%, 11.1%, 15.2%, 19.4%, 16.6%, 23.6%, and 6.9%. Further, a strong correlation was observed between the abundance of ß-lactamase-producing strains and IUS genes. CONCLUSIONS: Based on our knowledge from this study, the association between ß-lactamase production and IUS genes in A. baumannii plays an essential role in the emergence of drug-resistant strains.

Emergence of tigecycline-resistant Klebsiella pneumoniae ST11 clone in patients without exposure to tigecycline.

INTRODUCTION: Tigecycline is a unique class of semi-synthetic glycylcyclines developed to treat infections caused by multidrug-resistant Klebsiella pneumoniae. In the past decades, eight tigecycline-resistant Acinetobacter baumannii isolates have been identified in Tehran and no Klebsiella pneumoniae has been reported. METHODOLOGY: To elucidate the mechanism of K. pneumoniae efflux pump-mediated resistance, the expression of efflux pump genes (oqxA, oqxB, acrA, acrB, tolC) and regulators (acrR, ramA, marA, soxS, rarA, rob) was investigated by real-time RT-PCR. Multilocus sequence typing (MLST) of tigecycline-resistant strains was also performed. RESULTS: Compared to the tigecycline sensitive strain K32 (negative control), all resistant strains showed higher expression levels of efflux genes and regulatory factors. Three tigecycline-resistant strains (K53, K67, K79) showed higher levels of rarA expression (38.1-fold, 41-fold and 24-fold, respectively) and oqxB pump gene (48.2-fold, 60-fold and 58-fold, respectively). The increased expression of acrB was associated with the expression of ramA. However, to the best of our knowledge, studies on the mechanisms of resistance of K. pneumoniae strains to tigecycline are limited, especially in developing countries such as Iran. CONCLUSIONS: In the present study, we found that both AcrAB-TolC and OqxAB efflux pumps may play an important role in tigecycline resistance in K. pneumoniae isolates. Finally, the emergence of ST11 molecular type of resistant isolates should be monitored in hospitals to identify factors leading to tigecycline resistance.

Improved antibacterial function of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus.

The objective of this study was to assess the antibacterial activity of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus 544. Rifampicin-loaded solid lipid nanoparticles were prepared by a modified microemulsion/sonication method and characterized. The results showed the average size about 319.7 nm, PI about 0.20 and zeta potential about 18.4 mv, encapsulation efficacy and drug-loading were equal to 95.78 and 34.2%, respectively, with a spherical shape. Drug release lasted for 5 days. The antibacterial activity was statistically significant with p < .05 in bacterial and cell culture media compared to free Rifampicin. It can be concluded that solid lipid nanoparticles can be considered as a promising delivery system for improving the antibacterial activity of Rifampicin against Brucella abortus.