Prevalence of Virulence Genes and Their Association with Antimicrobial Resistance Among Pathogenic E. coli Isolated from Egyptian Patients with Different Clinical Infections.

INTRODUCTION: Escherichia (E.) coli can cause intestinal and extra-intestinal infections which ranged from mild to life-threatening infections. The severity of infection is a product of many factors including virulence properties and antimicrobial resistance. OBJECTIVES: To determine the antibiotic resistance pattern, the distribution of virulence factors and their association with one another and with some selected resistance genes. METHODS: Virulence properties were analyzed phenotypically while antimicrobial susceptibility was tested by Kirby-Bauer agar disc diffusion method. In addition, 64 E. coli isolates were tested for 6 colicin genes, fimH, hlyA, traT, csgA, crl virulence genes and bla-CTX-M-15, bla-oxa-2 , and bla-oxa-10 resistance genes by polymerase chain reaction (PCR). RESULTS: Extra-intestinal pathogenic E. coli isolated from urine and blood samples represented a battery of virulence factors and resistance genes with a great ability to produce biofilm. Also, a significant association (P<0.05) among most of the tested colicin, virulence and resistance genes was observed. The observed associations indicate the importance and contribution of the tested factors in the establishment and the progress of infection especially with Extra-intestinal E. coli (ExPEC) which is considered a great challenging health problem. CONCLUSION: There is a need for studying how to control these factors to decrease the rate and the severity of infections. The relationship between virulence factors and resistance genes is complex and needs more studies that should be specific for each area.

B/O plasmid R16 from 1956 carries an In1-like class 1 integron embedded in a complex region containing parts of the Acinetobacter baumannii AbaR resistance island.

The IncB/O multiresistance plasmid R16, recovered in 1956 and used in experimental studies of B/O plasmid features, was sequenced. The resistance genes are all within a class 1 integron closely related to In1 containing the cassette array oxa2-aadA1-oxa2-orfD and the sul1 gene in the 3'-conserved segment (3'-CS), with Tn10, containing tetA(B), inserted just inside the 3'-CS. The integron is part of a 25,144 bp region inserted in the plasmid backbone, bounded on only one side by a truncated Tn6018 and flanked by a 4 bp duplication. Most of the 82,026 bp R16 backbone is almost identical to that of the B/O plasmid R805a. However, two short regions containing genes of unknown function are <95% identical to the corresponding regions of R805a, and were likely acquired from a related plasmid. The insertion in R16 is related to one in the I1 plasmid pSE69-3861-1, which is embedded at the same position in an almost 11 kb segment of R16 backbone. In pSE69-3861-1, Tn6018 is complete, and two regions previously seen only in AbaR type islands of GC1 Acinetobacter baumannii are present. One contains a top topoisomerase gene and the second contains a resX resolvase gene. These regions are identical to the corresponding parts of AbaR islands. Thus, the complete sequence of R16 sheds light on the role of homologous recombination in the evolution of plasmid backbones and the acquisition of antibiotic resistance genes by I-complex plasmids, as well as on the formation of the AbaR islands of GC1 A. baumannii.

High prevalence of TEM, VIM, and OXA-2 beta-lactamases and clonal diversity among Acinetobacter baumannii isolates in Turkey.

INTRODUCTION: Acinetobacter baumannii is an opportunistic pathogen that causes nosocomial infections with high mortality. Treatment options are limited owing to its resistance to numerous antibiotics. Here, we sought to determine the antibiotic susceptibilities of A. baumannii isolates, investigate clonal relationship among the strains, and determine the frequency of beta-lactamase resistance genes. METHODOLOGY: The identification and antibiotic susceptibilities of 69 A. baumannii strains were determined using a BD-Phoenix automated system. The presence of blaOXA-2, blaOXA-10, blaOXA-23, blaOXA-24/40, blaOXA-51, blaOXA-58, blaTEM, blaSHV, blaIMP, blaVIM, and blaGIM genes were investigated using polymerase chain reaction (PCR), and clonal relatioships among the isolates were determined using pulsed-field gel electrophoresis (PFGE). RESULTS: All strains were resistant to ampicillin-sulbactam, gentamicin, cefepime, ciprofloxacin, and ceftriaxone. While 65 of the 69 strains (94.2%) were resistant to piperacillin-tazobactam, amikacin, imipenem, and meropenem, all strains were susceptible to tigecycline and colistin. The frequencies of blaOXA-51, blaOXA-23, blaTEM, blaOXA-2, blaVIM, and blaSHV were 100%, 94.2%, 53.6%, 21.7%, 14.5%, and 2.9%, respectively. Based on PFGE results, 56 of the 69 strains were clonally related, and the clustering rate was 81.2%. No common outbreak isolate was detected. CONCLUSIONS: The most prevalent OXA genes were blaOXA-51, blaOXA-23, and blaOXA-2. Furthermore, blaTEM, blaSHV, and blaVIM, which are common in Enterobacterales and Pseudomonas spp, were detected, suggesting horizontal gene transfer had occurred between bacteria. No single clone outbreak was detected by PFGE. However, multiclonal spread and the high clustering rate suggest cross-contamination. Therefore, in future, more effective infection control measures must be implemented.

Synthesis of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives and their biological evaluation against protein tyrosine phosphatase 1B.

A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against protein tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 µm and can be used as a novel lead compound for the design of inhibitors of protein tyrosine phosphatase 1B.

Dissemination of IMP-1 and OXA Type beta-Lactamase in Carbapenem-resistant Acinetobacter baumannii / 대한진단검사의학회지

BACKGROUND: Acinetobacter baumannii is an aerobic, gram-negative, glucose-nonfermenting bacterium, which has emerged as a serious opportunistic pathogen. In recent years, the increasing instance of carbapenem-resistant A. baumannii producing metallo-beta-lactamases (MBLs) or OXAtype beta-lactamases is causing a serious clinical problem. In this study, we investigated the prevalence of Ambler class A, B, and D beta-lactamases and their extended-spectrum derivatives in carbapenem-resistant A. baumannii isolates. METHODS: A total of 31 consecutive, non-duplicate, carbapenem-resistant A. baumannii were isolated from three university hospitals in the Chungcheong province of Korea. The modified Hodge and inhibitor-potentiated disk diffusion tests were conducted for the screening of carbapenemase and MBL production, respectively. PCR and DNA sequencing were performed for the detection of beta-lactamase genes. We also employed the enterobacterial repetitive intergenic consensus (ERIC)-PCR method for the epidemiologic study. RESULTS: Twenty-three of 31 isolates harbored bla(OXA-2) (51.6%), bla(OXA-23) (22.6%), bla(IMP-1) (48.4%),and bla(VIM-2) (3.2%). All of the OXA-2-producing strains also evidenced MBLs. The strains that harbored bla(OXA-23) were isolated only in hospital C, and only in a limited fashion. The ERIC-PCR pattern of the five OXA-23 strains indicated that the isolates were closely related in terms of clonality. The six strains producing IMP-1 isolated from hospital A were confirmed to be identical strains. CONCLUSIONS: A. baumannii strains harboring IMP-1 or OXA-type beta-lactamases are currently widely distributed throughout the Chungcheong province of Korea. The most notable finding in this study was that a bla(OXA-2)-producing A. baumannii harboring MBL, which has not been previously reported, can also lead to outbreaks.