Antibiotic resistance and frequency of class 1 integrons among Pseudomonas aeruginosa isolates obtained from wastewaters of a burn center in Northern Iran.

BACKGROUND: Pseudomonas aeruginosa, being responsible of a broad variety of infections, is considered an important nosocomial pathogen. The emergence of multiple-drug resistance among strains of P. aeruginosa appeared as a further public health concern. Due to the considerable ability of multiple-drug resistant P. aeruginosa strains to transmit themselves in the environment, we aimed to investigate the association of class 1 integrons with the antibiotic resistance profile of P. aeruginosa strains isolated from hospital wastewaters. METHODS: In this cross-sectional study, a total of 100 P. aeruginosa isolates were obtained from raw wastewater samples from February 2010 to January 2011 in a Teaching Burn Hospital in Guilan province. All isolates were identified as P. aeruginosa using standard microbiological tests. Antibiotic susceptibility was investigated using the disk diffusion method according to Clinical and Laboratory Standards Institute recommendations. All isolates were assayed for the presence of the class 1 integrons gene by PCR. RESULTS: Overall, 30 (30%) P. aeruginosa isolates were positive for the presence of class 1 integrons. The highest antibiotic resistance rates in both integron-positive and -negative isolates belonged to cephalexin and cephazolin, with 100% resistance. Amikacin and ciprofloxacin with the lowest level of resistance (13.3%) were the effective antibiotics against integron-positive isolates. The rates of MDR isolates were significantly higher among integron-positive isolates with 43.3% compared to negative isolates with 22.9% (P < 0.05). CONCLUSION: The results highlight the importance of class 1 integrons in multiple antibiotic resistance among P. aeruginosa isolates. Moreover, the spread of hospital derived wastewaters in the environment can be regarded as the origin of significant reservoirs for antibiotic-resistant pathogens.

Core promoter STRs: novel mechanism for inter-individual variation in gene expression in humans.

In a genome-scale analysis of the composition of core promoter sequences, we have recently shown that approximately 25% of the human protein-coding genes have at least one short tandem repeat (STR) of 3-repeats in their core promoters (i.e. the interval between -120 to +1). Through their nucleosome processing effect, GA-repeats play a crucial role in the regulation of gene transcription. In this study, we chose the human SRY (sex determining region Y)-box 5 (SOX5) gene as a prototype of the GA-rich core promoters to investigate the role of core promoter GA-STRs in gene expression. The human SOX5 gene is indispensable for diverse embryonic developmental processes, ranging from oligodendrocyte development and corticogenesis to chondrogenesis, and regulation of the cell cycle. Whereas the absolute ratio of 99% of the genes range between 0.2 and 2, the composition of the core promoter of the two most ubiquitously expressed mRNAs of the human SOX5 gene (transcripts ID: ENST00000451604 and ENST00000309359) is exceptionally rich in purine nucleotides (purine/pyrimidine ratio: 61.5). Indeed, this core promoter is an island of four tandem GA-STRs, and lacks the known TATA and TATA-less elements for gene transcription. Evolutionary conservation of this region between human and mouse (75% homology) supports important functional role for this promoter. In this study, we show that this nucleotide composition is indeed a potent promoter (p<1×10(-10)), and different haplotypes across the region result in significant difference in gene expression (p<1×10(-6)). To our knowledge, this is the first report of functional STRs in a human gene core promoter. Based on our search on the core promoters of the entire human protein-coding genes annotated in the GeneCards database (19,927genes) for the presence of pure GA-STRs, 429 genes contain at least one GA(3)-repeat in their core promoter. Core promoters with pure GA-STRs of GA(4) and above were observed in 61 genes. Our data unravel a novel mechanism for inter-individual variation in gene expression and complex traits/phenotypes through core promoter GA-STRs.