Emergence and spread of NDM-1 producer Enterobacteriaceae with contribution of IncX3 plasmids in the United Arab Emirates.

Among 28 clinically relevant, carbapenem non-susceptible Enterobacteriaceae isolates collected in 2009-2011 in the United Arab Emirates three Klebsiella pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Citrobacter freundi were identified to produce NDM-1 carbapenemase. Unexpectedly, with the exception of a K. pneumoniae strain, sequence type ST11, originally acquired in India and subsequently spread nosocomially in the UAE, the majority of the strains could not be directly linked to foreign travel. All isolates harboured the blaNDM-1 gene on plasmids of IncA/C, IncHI1b and IncX3 types, or were untypable. IncX3 type plasmids with a mass of 50 kb and with the same or highly similar restriction patterns, with regions flanking the blaNDM-1 gene identical to the IncX3 NDM plasmids described from China were present in three different species, Enterobacter cloacae, Escherichia coli and C. freundii. Our findings strongly support the assumptions that, beyond the Indian subcontinent, the Middle East is an important reservoir of NDM-producing organisms. Furthermore, we also provide evidence that IncX3 plasmids, recently implicated in the spread of blaNDM-1 in China, have been widely distributed and are important vehicles of the inter-species spread of the NDM-1 gene.

The rapidly emerging ESBL-producing Escherichia coli O25-ST131 clone carries LPS core synthesis genes of the K-12 type.

The clone Escherichia coli O25 ST131, typically producing extended-spectrum beta-lactamases (ESBLs), has spread globally and became the dominant type among extraintestinal isolates at many parts of the world. However, the reasons behind the emergence and success of this clone are only partially understood. We compared the core type genes by PCR of ESBL-producing and ESBL-nonproducing strains isolated from urinary tract infections in the United Arab Emirates and found a surprisingly high frequency of the K-12 core type (44.6%) among members of the former group, while in the latter one, it was as low (3.7%), as reported earlier. The high figure was almost entirely attributable to the presence of members of the clone O25 ST131 among ESBL producers. Strains from the same clone isolated in Europe also carried the K-12 core type genes. Sequencing the entire core operon of an O25 ST131 isolate revealed a high level of similarity to known K-12 core gene sequences and an almost complete identity with a recently sequenced non-O25 ST131 fecal isolate. The exact chemical structure and whether and how this unusual core type contributed to the sudden emergence of ST131 require further investigations.

Change in meticillin-resistant Staphylococcus aureus clones at a tertiary care hospital in the United Arab Emirates over a 5-year period.

AIMS: Meticillin-resistant Staphylococcus aureus (MRSA) strains isolated in Tawam Hospital, a tertiary care hospital in the United Arab Emirates, were examined in order to understand the reasons for a doubling of its incidence between 2003 and 2008 while maintaining the same infection control measures. METHODS: All consecutive non-duplicate clinically relevant MRSA isolates recovered between January and December 2003 and between May and October 2008 were studied. The antibiotic susceptibility, pulsed field gel electrophoresis, toxin gene, staphylococcal cassette chromosome mec (SCCmec), spa, agr and multilocus sequence types of the strains were tested. RESULTS: In 2003, typical healthcare-associated (HA-MRSA) genotypes (ST239-MRSA-III, ST22-MRSA-IV and ST5-MRSA-II) represented the majority (61.5%) of the isolates. By 2008 this pattern had changed and clonal types considered as community-associated (CA) MRSA comprised 73.1% of the strains with ST80-MRSA-IV, ST5-MRSA-IV and ST1-MRSA with non-typable SCCmec types being the most frequent. However, further epidemiological investigations showed that only one-third of the CA-MRSA infections were actually acquired in the community, indicating that CA-MRSA clones have entered and spread within the hospital. CONCLUSIONS: The emergence of CA-MRSA clones with subsequent entry to and spread within the hospital has contributed to the increasing incidence of MRSA observed in Tawam Hospital and probably also in other hospitals in the UAE.

HER-2/neu Ile655Val polymorphism and the risk of breast cancer.

Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis. Genotyping studies have addressed the association of codon 655 isoleucine to valine polymorphism located in the transmembrane coding region and the risk of breast cancer, but the results are inconsistent. In this study, we investigated the association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer in a Sudanese population. In addition, the joint effects of HER-2/neu variants and our previously reported ESR1C325G polymorphism were tested for their association with breast cancer risk. Candidate single nucleotide polymorphism (SNP) in HER-2/neu Ile655Val [db SNP rs1136200] was genotyped in breast cancer patients and in healthy controls that were randomly selected from the same age group as the patients. Genotyping was performed using a high-throughput allelic discrimination method using real-time PCR, and data on clinical features and demographic details were collected. Associations between genotype and breast cancer were assessed by means of logistic regression. The prevalence of Val/Val genotype was similar in patients of breast cancer and control subjects. In comparison with the Ile/Ile genotype, the Ile/Val had a borderline significantly (P= 0.06) higher risk of breast cancer (OR = 2.95, 95% CI: 0.97-8.96). Regarding the genotypic and allelic frequencies stratified by age and menopausal status, there were no significant associations. A significantly higher risk of breast cancer was observed among homozygous carriers of ESR1325 CC genotype and heterozygous carriers of HER-2/neu655 Ile/Val genotype (P= 0.05; adjusted OR = 4.9, 95% CI: 1.0-24). The association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer was borderline significant with the heterozygous carrier being at higher risk. However, the frequency of different polymorphic variants varies with ethnicity. The results of this study suggest that a significant gene-gene interaction between ESR1325C (previously reported) and HER-2/neu Ile655Val variants may jointly contribute to a higher risk of breast cancer.

Estrogen receptor alpha gene polymorphism and breast cancer.

Estrogen and estrogen receptors play important roles in the proliferation and development of breast cancer. Several genetic alterations identified in the estrogen receptor alpha gene (ESR1) are thought to influence the expression or function of this protein, and many have been evaluated for their role in breast cancer predisposition. The aim of this study was to evaluate the role of the C325G single nucleotide polymorphism (SNP) in the ESR1 in predisposition to breast cancer. The candidate SNP C325G in ESR1, exon 4 was genotyped in breast cancer patients and in healthy controls that were age and sex matched. Genotyping was performed using both single-stranded conformational polymorphism (SSCP) and a higher throughput allelic discrimination method using real-time PCR. Data on clinical features and demographic details were collected. Significant association of breast cancer risk was shown in the subgroup of women 50 years and younger who had the C allele (OR: 2.28, 95% CI: 1.10-4.72) (P= 0.03). However, the overall susceptibility to breast cancer was not significant, although all estimates were in the direction of a higher risk in women with CC genotypes. This study found significant evidence that polymorphism within the low penetrance ESR1 is associated with breast cancer susceptibility in women of 50 years or younger. There is also an indication that G allele is protective (compared to C allele).