Rapid emergence of aggressive, multidrug-resistant Mycobacteria strain represents the main cause of the current antimycobacterial-drug crisis and status of tuberculosis (TB) as a major global health problem. The relatively low-output of newly approved antibiotics contributes to the current orientation of research towards alternative antibacterial molecules such as advanced materials. Nanotechnology and nanoparticle research offers several exciting new-concepts and strategies which may prove to be valuable tools in improving the TB therapy. A new paradigm in antituberculous therapy using silver nanoparticles has the potential to overcome the medical limitations imposed in TB treatment by the drug resistance which is commonly reported for most of the current organic antibiotics. There is no doubt that AgNPs are promising future therapeutics for the medication of mycobacterial-induced diseases but the viability of this complementary strategy depends on overcoming several critical therapeutic issues as, poor delivery, variable intramacrophagic antimycobacterial efficiency, and residual toxicity. In this paper, we provide an overview of the pathology of mycobacterial-induced diseases, andhighlight the advantages and limitations of silver nanoparticles (AgNPs) in TB treatment.

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Introduction: The occurrence of pathogenic strains in poultry meat is of growing concern in Romania. Another problem found on a global level is the continuous increase of antimicrobial resistance in bacteria isolated from food. This study aimed to evaluate the prevalence of pathogenic bacteria in poultry carcasses obtained in Romania in 2012-2013 and to reveal the most prevalent patterns of antimicrobial resistance in the isolated strains. Methodology: A total of 144 broiler chicken carcasses were evaluated according to classical microbiological methods. The DNA was extracted from the bacterial colonies and the resistance genes were identified by PCR. Results: In 2012, 47.2% of the samples revealed at least one of the following bacteria: Campylobacter jejuni (9.72%; n = 7), Salmonella enterica serotype Enteritidis (4.17%; n = 3), Listeria monocytogenes (15.28%; n = 11), and Escherichia coli (16.67%; n = 12). In 2013, the number of positive samples of pathogenic bacteria decreased, although Campylobacter jejuni was isolated in a higher percentage (20.8% vs. 9.72%). The percentage of multidrug-resistant (MDR) bacteria was high (23%); the most prevalent pattern included resistance to tetracycline, sulfonamides, and quinolones/fluoroquinolones. All the resistant Salmonella and E. coli strains were tested for the presence of characteristic resistance genes (Kn, bla TEM , tetA, tetB, tetG, DfrIa, aadA1a, Sul) and revealed that these isolates represent an important reservoir in the spread of this phenomenon. Conclusions: Our findings suggest that Romania urgently needs an integrated surveillance system within the entire chain, for drug-resistant pathogens isolated from poultry meat.

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Milk and dairy products are considered the main sources of saturated fatty acids, which are a valuable source of nutrients in the human diet. Fat composition can be adjusted through guided nutrition of dairy animals but also through selective breeding. Recently, a dinucleotide substitution located in the exon 8 of the gene coding for acyl CoA: diacylglycerol acyltransferase 1 (DGAT1), that alters the amino acid sequence from a lysine to an alanine (p.Lys232Ala) in the mature protein, was shown to have a strong effect on milk fat content in some cattle breeds. Therefore, the objectives of this work were to study the occurrence of the DGAT1 p.Lys232Ala polymorphism in Romanian Holstein cattle and Romanian Buffalo breeds and to further investigate its possible influence on fat percentage and fatty acid profiles. The results obtained in this study show that in Romanian Holstein cattle the K allele is associated with increased fat percentage and higher levels of C16:0 and C18:0 fatty acids. The ratio of saturated fatty acids versus unsaturated fatty acids (SFA/UFA) was also higher in KK homozygous individuals, whereas the fractions of C14:0, unsaturated C18 decreased. The DGAT1 p.Lys232Ala polymorphism revealed a high genetic variance for fat percentage, unsaturated C18, C16:0, and SFA/UFA. Although the effect of this polymorphism was not so evident for short chain fatty acids such as C4:0-C8:0, it was significant for C14:0 fatty acids. We concluded that selective breeding of carriers of the A allele in Romanian Holsteins can contribute to improvement in unsaturated fatty acids content of milk. However, in buffalo, the lack of the A allele makes selection inapplicable because only the K allele, associated with higher saturated fatty acids contents in milk, was identified.

BackgroundGastroenteritis attributable to Salmonella enterica and the continuous increase in antimicrobial resistance of this gut pathogen, which compromises the use of previously effective treatments, is of great concern for public health. This study was conducted in order to investigate the presence of plasmid-mediated quinolone resistance (PMQR) determinants and β-lactamase-encoding genes, in S.enterica, isolated from humans, one companion animal and food. Moreover, the study aimed to identify potential vehicles of transmission of resistant strains to humans, with focus on food products (meat).MethodsA total of 20 S. enterica isolates recovered from food (chicken and pork meat), one companion animal and humans (stool samples), were examined for their serotype, antimicrobial susceptibility and the presence of PMQR and β-lactamase-encoding genes. Moreover, the genetic relatedness of nine Salmonella Infantis and ten Salmonella Enteritidis isolates was analyzed by pulsed-field gel electrophoresis (PFGE).ResultsAmong all isolates, 15 (75%) were multidrug-resistant (MDR) and the majority of them proved to be resistant to nalidixic acid and fluoroquinolones (FQs) (ciprofloxacin and levofloxacin). Twelve isolates (60%) harboured at least one PMQR gene [qnrA, qnrB, qnrS, aac (6′)-Ib-cr or qepA] while seven isolates (35%) carried at least one β-lactamase-encoding gene (blaTEM, blaPSE-1, blaSHV or blaCTX-M). Moreover, two or more PMQR or β-lactamase-encoding genes co-existed in a single S.enterica isolate. A number of nine Salmonella Infantis, as well as the majority of Salmonella Enteritidis isolates analyzed by PFGE proved to be closely related.ConclusionsThe study demonstrated the co-existence of PMQR and β-lactamase-encoding genes among the Salmonella isolates recovered and confirmed that multiple mechanisms might be involved in the acquisition and spread of resistance determinants. The close genetic relatedness between the clinical and foodborne S. enterica isolates, suggested that chicken meat might be a possible cause of human salmonellosis in our country, during the study period. Results of this study might improve understanding of the antimicrobial resistance mechanisms and transmission dynamics of Salmonella spp. Here, we report for the first time the presence of PMQR and β-lactamase-encoding genes in S. enterica isolates, recovered from humans, one companion animal and food, in Romania.

The GM2-gangliosidoses are neurological diseases causing premature death, thus developing effective treatment protocols is urgent. GM2-gangliosidoses result from deficiency of a lysosomal enzyme β-hexosaminidase (Hex) and subsequent accumulation of GM2 gangliosides. Genetic changes in HEXA, encoding the Hex α subunit, or HEXB, encoding the Hex β subunit, causes Tay-Sachs disease and Sandhoff disease, respectively. Previous studies have showed that a modified human Hex μ subunit (HEXM) can treat both Tay-Sachs and Sandhoff diseases by forming a homodimer to degrade GM2 gangliosides. To this end, we applied this HEXM subunit in our PS813 gene editing system to treat neonatal Sandhoff mice. Through AAV delivery of the CRISPR system, a promoterless HEXM cDNA will be integrated into the albumin safe harbor locus, and lysosomal enzyme will be expressed and secreted from edited hepatocytes. Four months after the i.v. of AAV vectors, plasma MUGS and MUG activities reached up to 144-and 17-fold of wildtype levels (n=10, p<0.0001), respectively. More importantly, MUGS and MUG activities in the brain also increased significantly compared with untreated Sandhoff mice (p<0.001). Further, HPLC-MS/MS analysis showed that GM2 gangliosides in multiple tissues, except the brain, of treated mice were reduced to normal levels. Rotarod analysis showed that coordination and motor memory of treated mice were improved (p<0.05). Histological analysis of H&E stained tissues showed reduced cellular vacuolation in the brain and liver of treated Sandhoff mice. These results Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

This study was conducted in order to assess the antimicrobial resistance patterns of E. coli isolated from young animals affected between 1980 and 2016. The selected isolates for this study (n=175) carried stx1/stx2 genes and the most prevalent type of pathogenic E. coli found belonged to serogroup O101, antigen (K99)–F41 positive. All STEC-positive isolates were tested for susceptibility to 11 antimicrobials. Multidrug resistance (MDR) increased from 11% during the 1980s to 40% between 2000 and 2016. Resistance to tetracycline and streptomycin was the most frequent co-resistance phenotype (37%). Co-resistance to tetracycline and sulfonamide was found in 21% of E. coli isolates, while the MDR pattern to tetracycline, sulfonamide, and streptomycin was observed in 12% of the strains tested. Only 8% of isolates were co-resistant to tetracycline, ampicillin, streptomycin, and sulfonamide. The most common resistance genes found were those encoding for tetracycline, sulphonamides, and streptomycin, with 54% (n=95) of the tested isolates containing at least one of the genes encoding tetracycline resistance. A total of 87% of E. coli that tested positive for tetracycline (tetA, tetB, and tetC) and sulphonamide (sul1) resistance genes were isolated between 2000 and 2016. A large number of isolates (n=21) carried int1 and a nucleotide sequence analysis revealed that all class 1 integron gene cassettes carried sul1, tet, and dfrA1 resistance genes. An increase was observed in the level of resistance to antimicrobials in Romania, highlighting the urgent need for a surveillance and prevention system for antimicrobial resistance in livestock in Eastern Europe.