Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
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Enteroaggregative Escherichia coli (EAEC), an enteric pathogen, causes persistent diarrhea in children, HIV-infected individuals, and travelers in economically developing countries. However, the pathogenesis of EAEC infection is not well understood. This study aimed to characterize EAEC in Japan. Between 2012 and 2014, we identified 40 EAEC strains carrying the aggR gene at the Kawasaki City Institute for Public Health, Japan. We characterized these strains using O:H-antigen typing, polymerase chain reaction (for pCVD432, astA, extended-spectrum beta-lactamase, and 4 aggregative adherence fimbriae genes), HEp-2 cell adherence, clump formation, and antimicrobial susceptibility testing. We were able to classify the 40 EAEC strains into 20 O:H types. Although specific O:H types were not correlated with HEp-2 cell aggregative adherence, all the O99:H10, O131:H27, and O176:H34 EAEC strains that were the most frequent O:H types detected in this study showed co-resistance to ampicillin, sulfamethoxazole-trimethoprim, and tetracycline. Based on results of the adhesion assay and detection of virulence-related genes, no significant difference was found between asymptomatic and symptomatic cases. Irrespective of the origin, their potential for virulence was retained. Further characterization is vital to determine whether EAEC is virulent in Japan.
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PMID:Phenotypic and Molecular Characterization of Enteroaggregative Escherichia coli Isolated in Kawasaki, Japan. 2836 79

Bangladesh is considered as a high-risk country for emerging infectious diseases because of its high population density, poverty, and unhygienic conditions. Although control efforts have primarily been focused on major infectious diseases such as diarrheal diseases, tuberculosis, malaria, and HIV infection, the prevalence and impact of many local or minor infectious diseases are still unclarified in this country. In this review, we present our recent experience and outcomes of collaborative research on puerperal infection (PI), which is a poorly defined infectious disease in Bangladesh. PI is the most common complication during the perinatal period in developing countries. We investigated the incidence of individual species of aerobic bacteria causing PIs and their drug resistance, and the genetic traits of isolates during the two-year period (2010-2012). The common species of isolates from patients with PIs were Escherichia coli, Enterococcus faecalis, Staphylococcus haemolyticus, Proteus mirabilis, Staphylococcus aureus, and Klebsiella pneumoniae. A remarkable finding was the high rates of resistance to cephalosporins among Gram-negative bacteria harboring extended-spectrum beta-lactamase genes, which were associated with carbapenem resistance in a few isolates. This study defined the importance of control of antimicrobial resistance in Bangladesh, and provided suggestions for the future direction of collaborative research on infectious diseases in Bangladesh.
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PMID:Collaborative Research on Puerperal Infections in Bangladesh. 2855 90

The substitution rates of transitions are higher than expected by chance relative to those of transversions. Many have argued that selection disfavors transversions, as nonsynonymous transversions are less likely to conserve biochemical properties of the original amino acid. Only recently has it become feasible to directly test this selective hypothesis by comparing the fitness effects of a large number of transition and transversion mutations. For example, a recent study of six viruses and one beta-lactamase gene did not find evidence supporting the selective hypothesis. Here, we analyze the relative fitness effects of transition and transversion mutations from our recently published genome-wide study of mutational fitness effects in influenza virus. In contrast to prior work, we find that transversions are significantly more detrimental than transitions. Using what we believe to be an improved statistical framework, we also identify a similar trend in two HIV data sets. We further demonstrate a fitness difference in transition and transversion mutations using four deep mutational scanning data sets of influenza virus and HIV, which provided adequate statistical power. We find that three of the most commonly cited radical/conservative amino acid categories are predictive of fitness, supporting their utility in studies of positive selection and codon usage bias. We conclude that selection is a major contributor to the transition:transversion substitution bias in viruses and that this effect is only partially explained by the greater likelihood of transversion mutations to cause radical as opposed to conservative amino acid changes.
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PMID:Evidence for the Selective Basis of Transition-to-Transversion Substitution Bias in Two RNA Viruses. 2902 87

Bacterial infections remain a leading killer worldwide, which is worsened by the continuous emergence of antibiotic resistance. In particular, antibiotic-resistant Enterobacteriaceae are prevalent and extremely difficult to treat. Repurposing existing drugs and improving the therapeutic potential of existing antibiotics represent an attractive novel strategy. Azidothymidine (AZT) is an antiretroviral drug which is used in combination with other antivirals to prevent and to treat HIV/AIDS. AZT is also active against Gram-negative bacteria but has not been developed for that purpose. Here, we investigated the in vitro and in vivo efficacy of AZT in combination with colistin against antibiotic-resistant Enterobacteriaceae, including strains producing extended-spectrum beta-lactamases (ESBLs) or New Delhi metallo-beta-lactamase 1 (NDM) or carrying mobilized colistin resistance (mcr-1). The MIC was determined using the broth microdilution method. The combined effect of AZT and colistin was examined using the checkerboard method and time-kill analysis. A murine peritoneal infection model was used to test the therapeutic effect of the combination of AZT and colistin. The fractional inhibitory concentration index from the checkerboard assay demonstrated that AZT synergized with colistin against 61% and 87% of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains, respectively, 100% of NDM-1-producing strains, and 92% of mcr-1-producing E. coli strains. Time-kill analysis demonstrated significant synergistic activities when AZT was combined with colistin. In a murine peritoneal infection model, AZT in combination with colistin showed augmented activities of both drugs in the treatment of NDM-1 K. pneumoniae and mcr-1 E. coli infections. The AZT and colistin combination possesses a potential to be used coherently to treat antibiotic-resistant Enterobacteriaceae infections.
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PMID:Azidothymidine Produces Synergistic Activity in Combination with Colistin against Antibiotic-Resistant Enterobacteriaceae. 3037 98

In the present study, we identified and evaluated the antibiotic susceptibility of 96 independent, aerobic, Gram-negative bacillus isolates from 255 Thai HIV-positive adults who were on Highly-active anti-retrovirus therapy (HAART) medication. Another 46 isolates from HIV non-HAART individuals, vertically transmitted HIV-positive individuals, and non-HIV controls were included for comparison. A total of 103 strains were tested for antibiotic susceptibility using disc diffusion for screening and E-test for minimal inhibitory concentration determination, with special attention on extended-spectrum beta-lactamase (ESBL) isolates. Pseudomonas aeruginosa, Pseudomonas luteola, Burkholderia cepacia, Aeromonas hydrophila, Klebsiella, and Enterobacter species were the most common bacteria. All strains were resistant against penicillin, amoxicillin, clindamycin, and metronidazole. No ESBL isolates were found.
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PMID:Non-oral, aerobic, Gram-negative bacilli in the oral cavity of Thai HIV-positive patients on Highly-active anti-retrovirus therapy medication. 3070 96


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