Infected foot ulcers in male and female diabetic patients: a clinico-bioinformative study

<p>Abstract</p> <p>Background</p> <p>The study aimed at (i) characterizing the mode of transmission of <it>bla</it>_CTX-Mand <it>bla</it>_TEM-1among extended-spectrum-β-lactamase (ESBL)-producing <it>Escherichia coli </it>strains isolated from infected diabetic foot ulcers, and (ii) identifying the risk factors for "sex-associated multidrug resistant Gram-negative bacterial (MDRGNB)-infection status" of the ulcers.</p> <p>Methods</p> <p>Seventy-seven diabetic patients having clinically infected foot ulcers were studied in a consecutive series. The <it>E. coli </it>strains isolated from the ulcers were screened for <it>bla</it>_CTX-M, <it>bla</it>_TEM-1, <it>armA</it>, <it>rmtA </it>and <it>rmtB </it>during the 2-year study-period. PCR amplified <it>bla</it>_CTX-Mgenes were cloned and sequenced. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was used for the analysis of genetic relatedness of the ESBL-producers. Risk factors for "sex-associated MDRGNB-infection status" of ulcers were assessed. Modeling was performed using Swiss-Model-Server and verified by Procheck and verify3D programmes. Discovery Studio2.0 (Accelrys) was used to prepare Ramachandran plots. Z-scores were calculated using 'WHAT IF'-package. Docking of cefotaxime with modeled CTX-M-15 enzyme was performed using Hex5.1.</p> <p>Results</p> <p>Among 51 <it>E. coli </it>isolates, 14 (27.5%) ESBL-producers were identified. Only 7 Class1 integrons, 2 <it>bla</it>_CTX-M-15, and 1 <it>bla</it>_TEM-1were detected. Ceftazidime and cefotaxime resistance markers were present on the plasmidic DNA of both the <it>bla</it>_CTX-M-15positive strains and were transmissible through conjugation. The residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 were found to make important contacts with cefotaxime in the docked-complex. Multivariate analysis proved 'Glycemic control at discharge' as the single independent risk factor.</p> <p>Conclusions</p> <p>Male diabetic patients with MDRGNB-infected foot ulcers have poor glycemic control and hence they might have higher mortality rates compared to their female counterparts. Plasmid-mediated conjugal transfer, albeit at a low frequency might be the possible mechanism of transfer of <it>bla</it>_CTX-M-15resistance marker in the present setting. Since the docking results proved that the amino acid residues Asn132, Glu166, Pro167, Val172, Lys234 and Thr235 of CTX-M-15 (enzyme) make important contacts with cefotaxime (drug) in the 'enzyme-drug complex', researchers are expected to duly utilize this information for designing more potent and versatile CTX-M-inhibitors.</p

Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health

Background: The emergence of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1) and its variants, worldwide, has raised amajor public health concern. NDM-1 hydrolyzes a wide range of β-lactam antibiotics, including carbapenems, which are the last resort of antibiotics for the treatment of infections caused by resistant strain of bacteria. Main body: In this review, we have discussed blaNDM-1variants, its genetic analysis including type of specific mutation, origin of country and spread among several type of bacterial species. Wide members of enterobacteriaceae, most commonly Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and gram-negative non-fermenters Pseudomonas spp. and Acinetobacter baumannii were found to carry these markers. Moreover, at least seventeen variants of blaNDM-type gene differing into one or two residues of amino acids at distinct positions have been reported so far among different species of bacteria from different countries. The genetic and structural studies of these variants are important to understand the mechanism of antibiotic hydrolysis as well as to design new molecules with inhibitory activity against antibiotics. Conclusion: This review provides a comprehensive view of structural differences among NDM-1 variants, which are a driving force behind their spread across the globe