Marie MA. J Korean Med Sci. 2012 Feb;27(2):190-193. http://dx.doi.org/10.3346/jkms.2012.27.2.190

Inflammation is pivotal to the pathogenesis of diabetes mellitus (DM), but pathological alterations of the neutrophil–lymphocyte ratio (NLR), an emerging inflammatory index in DM management, remains understudied. The aim of this study is to examine the relationship between NLR and glycemic control in the Saudi population. Gender, age, WBC count, and fasting blood glucose (FBG) were obtained from Al-Borg Medical Laboratories for 14,205 subjects. Means, prevalence, risk measures, and the diagnostic accuracy of elevated NLR and hyperglycemia (HG) were evaluated. Subjects with elevated NLR (>3) had significantly higher FBG (105.10 ± 0.33 vs. 114.0 ± 2.81) and NLR was significantly elevated in impaired fasting glycemia (IFG; 1.21 ± 0.01 vs. 1.25 ± 0.01) and HG (1.21 ± 0.01 vs. 1.39 ± 0.02). Elevations of NLR in HG but not in IFG persisted across all age groups except young males and elderly females. The prevalence of elevated NLR in hyperglycemic subjects was 4.12% compared to 2.16% in subjects with normal FBG. HG was more prevalent in subjects with elevated NLR (17.33% vs. 12.46%) who had a relative risk (RR) of 1.68 (95% CI = 1.38–2.06, p < 0.0001) and an odds ratio (OR) of 1.94 (95% CI = 1.48–2.56, p < 0.0001) to be hyperglycemic. Nevertheless, NLR failed to discriminate individuals with normal FBG from those with HG based on ROC curve analysis. Pathological fluctuations in NLR may serve as supportive evidence in DM management.

Background: Whole-genome sequencing is one of the best ways to investigate resistance mechanisms of clinical isolates as well as to detect and identify circulating multi-drug-resistant (MDR) clones or sub-clones in a given hospital setting. Methods: Here, we sequenced 37 isolates of Acinetobacter baumannii, 10 Klebsiella pneumoniae, and 5 Pseudomonas aeruginosa collected from the biobank of the hospital setting of the King Fahad Medical City. Complete phenotypic analyses were performed, including MALDI-TOF identification and antibiotic susceptibility testing. After the genome assembly of raw data, exhaustive genomic analysis was conducted including full resistome determination, genomic SNP (gSNP) analysis, and comparative genomics. Results: Almost all isolates were highly resistant to all tested antibiotics, including carbapenems and colistin. Resistome analysis revealed many antibiotic resistance genes, including those with resistance to β-lactams, aminoglycosides, macrolides, tetracyclines, sulfamids, quinolones, and phenicols. In A. baumannii isolates, the endemic carbapenemase bla_OXA-23 gene was detected in 36 of the 37 isolates. Non-synonymous mutations in pmrB were detected in almost all of the isolates and likely mediated colistin resistance. Interestingly, while classical analyses, such as MLST, revealed the predominance of an ST2 clone in A. baumannii isolates, the genomic analysis revealed the presence of five circulating sub-clones and identified several isolate transmissions between patients. In the 10 K. pneumoniae isolates, several resistance genes were identified, and the observed carbapenem resistance was likely mediated by overexpression of the detected extended-spectrum-β-lactamase (ESBL) genes associated with low membrane permeability as few carbapenemase genes were detected with just bla_OXA-48 in three isolates. Colistin resistance was mediated either by non-synonymous mutations in the MgrB regulator, PmrA, PmrB, and PhoQ proteins or the presence of the MCR-1 protein. Here, gSNP analysis also revealed the existence of bacterial clones and cases of isolate transmissions between patients. The five analyzed P. aeruginosa isolates were highly resistant to all tested antibiotics, including carbapenems mediated by loss or truncated OprD porin, and colistin resistance was associated with mutations in the genes encoding the PmrA, PmrB, or PhoQ proteins. Conclusion: We demonstrate here the usefulness of whole-genome sequencing to exhaustively investigate the dissemination of MDR isolates at the sub-clone level. Thus, we suggest implementing such an approach to monitor the emergence and spread of new clones or sub-clones, which classical molecular analyses cannot detect. Moreover, we recommend increasing the surveillance of the endemic and problematic colistin resistance mcr-1 gene to avoid extensive dissemination.

Marie MA, et al. Gut Liver. 2011 Sep;5(3):315-320. http://dx.doi.org/10.5009/gnl.2011.5.3.315

Marie MA. J Bacteriol Virol. 2010 Dec;40(4):159-162. http://dx.doi.org/10.4167/jbv.2010.40.4.159

We analysed nine Pseudomonas guariconensis-clade genomes from environmental and clinical sources across four continents to test whether carriage of acquired resistance is associated with the acquisition of mobile elements. FA-1, our tick-derived anchor from Hyalomma dromedarii on Saudi camels, sits at 87.52–87.94% ANI to the other genomes on the longest external branch of the core-genome ML phylogeny. In the current NCBI type-strain ANI taxonomy check, FA-1 is conspecific with the recently described Pseudomonas shiyinii type strain ST4 (98.05% ANI). The recently reported Vietnamese hospital-wastewater isolate KNHN1 groups within the sensu stricto clinical clade alongside USA-Nashville and India at 99.7%/99% (SH-aLRT/UFBoot) support. Across the nine genomes, three distinct carbapenemase architectures emerged: Dao (chromosomal KPC-2 + NDM-1 + AFM-5), Ethiopia (chromosomal NDM-1 × 2 + plasmid VIM-4), and Korea (plasmid VIM-2). Dao and Ethiopia chromosomes share a MOBH-family relaxase signal, extending the MOBH marker to the clinical compartment. MBL-positive genomes carried more mobile elements (Dao 55; Ethiopia 22; Korea 16; 16–55 hits) than MBL-negative comparators (0–8 hits), an unadjusted descriptive observation (n = 3 vs. 6). Ethiopia presented an integron-rich chromosomal and plasmid architecture (six structures), while Dao carried IS-bounded transposon islands on the chromosome. Three of four Dao chromosomal ICE predictions and one Ethiopia ICE prediction lay 27–50 kb from IS-bounded carbapenemase loci; a fourth Dao ICE was standalone and the major Ethiopia NDM-1 + OXA-10 cassette lacked an adjacent complete ICE prediction, indicating descriptive ICE-cassette proximity rather than functionally demonstrated mobility. Together, these findings are consistent with mobile-element acquisition as a plausible route for the emergence of clinical resistance within this clade, with environmental relatives retaining empty insertion sites at the AMR-cassette locus.