Correlation Analysis between Antibiotic Resistance Gene Profile and Susceptibility to Gentamicin, Clindamycin, and Minocycline in Clinically Isolated Methicillin-resistant Staphylococcus aureus

This study aimed to elucidate retrospectively the correlations between the genome and phenotype in clinical methicillin-resistant Staphylococcus aureus (MRSA) gentamicin (GEN), clindamycin (CLI), and minocycline (MIN) susceptibility using next-generation sequencing (NGS) technology. Ninety two MRSA strains were isolated from individual inpatients treated in Hiroshima University Hospital, Hiroshima, Japan, extracted for their genomic DNA, and sequenced using an Illumina® MiSeq sequencer to obtain their de novo whole-genome assembly. An in silico analysis using ResFinder was performed to obtain the genomic antimicrobial susceptibility profile which was analyzed together with GEN, CLI, and MIN minimum inhibitory concentration (MIC) levels. This study found aac(6’)aph(2”)+, spc+, ermA+, tetM+ MRSA strains were predominant (42/92) and were shown to exhibit >16 mg/L GEN (40/42), >4 mg/L CLI (26/42), and >8 mg/L MIN MIC levels (30/42). Associations between aac(6’)aph(2”) detections and GEN MIC levels (p <0.001), ermA detections and CLI MIC levels (p <0.001), and tetM detections and MIN MIC levels (p <0.001) were revealed in this study. Correlations between simultaneous detections of aac(6’) aph(2”)-spc-ermA-tetM and GEN MIC levels (φc= 0.398, p <0.001), CLI MIC levels (φc= 0.448, p <0.001), and MIN MIC levels (φc= 0.515, p <0.001) were revealed in this study. The genomicphenotypic correlation analyses in this study provided an insight of a rapid antimicrobial detection in MRSA using in silico genomic antimicrobial susceptibility profiling.This research was partially supported by a Grant-in-Aid for Scientific Research (A) (No.15H02567) from the Ministry of Education, Culture, Sports, Science, and Technology and those from Ministry of Health, Labor, and Welfare of the Government of Japan

Cancer Chemopreventive Ability of Conjugated Linolenic Acids

Conjugated fatty acids (CFA) have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA) are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1%) in natural products, conjugated linolenic acids (CLN) are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid). Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR)-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer

Evaluation and Characterization of Bacterial Metabolic Dynamics with a Novel Profiling Technique, Real-Time Metabolotyping

BACKGROUND: Environmental processes in ecosystems are dynamically altered by several metabolic responses in microorganisms, including intracellular sensing and pumping, battle for survival, and supply of or competition for nutrients. Notably, intestinal bacteria maintain homeostatic balance in mammals via multiple dynamic biochemical reactions to produce several metabolites from undigested food, and those metabolites exert various effects on mammalian cells in a time-dependent manner. We have established a method for the analysis of bacterial metabolic dynamics in real time and used it in combination with statistical NMR procedures. METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel method called real-time metabolotyping (RT-MT), which performs sequential (1)H-NMR profiling and two-dimensional (2D) (1)H, (13)C-HSQC (heteronuclear single quantum coherence) profiling during bacterial growth in an NMR tube. The profiles were evaluated with such statistical methods as Z-score analysis, principal components analysis, and time series of statistical TOtal Correlation SpectroScopY (TOCSY). In addition, using 2D (1)H, (13)C-HSQC with the stable isotope labeling technique, we observed the metabolic kinetics of specific biochemical reactions based on time-dependent 2D kinetic profiles. Using these methods, we clarified the pathway for linolenic acid hydrogenation by a gastrointestinal bacterium, Butyrivibrio fibrisolvens. We identified trans11, cis13 conjugated linoleic acid as the intermediate of linolenic acid hydrogenation by B. fibrisolvens, based on the results of (13)C-labeling RT-MT experiments. In addition, we showed that the biohydrogenation of polyunsaturated fatty acids serves as a defense mechanism against their toxic effects. CONCLUSIONS: RT-MT is useful for the characterization of beneficial bacterium that shows potential for use as probiotic by producing bioactive compounds

FMD, PWV, and Cardiovascular Events

Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

BackgroundThe usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.Methods and ResultsWe measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.ConclusionsIn patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

Bloodstream Infection Caused by Actinomyces neuii subsp. anitratus in a Patient with Breast Cancer: A Case Report and Literature Review

Actinomyces neuii can grow under aerobic culture conditions and shows a gram-positive rod morphology, similar to that of Corynebacterium spp. A. neuii is usually detected in local pus samples, and published cases of A. neuii bloodstream infections are rare. Here, we report a case of bloodstream infection caused by A. neuii subsp. anitratus. A 53-year-old woman with fever and hypotension was referred to our hospital. The patient underwent surgery for breast cancer and received chemotherapy after central venous (CV) port placement. On day 2, a blood culture in an anaerobic bottle yielded positive results, and A. neuii subsp. anitratus was identified via matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) and 16S rRNA sequencing. The patient was diagnosed with bloodstream infection caused by A. neuii subsp. anitratus with CV port infection. The CV port was removed and antibiotic treatment resulted in symptom improvement so the patient was discharged on day 28 of hospitalization. MALDI–TOF MS and 16S rRNA sequencing were found to be more useful for the identification of A. neuii than for phenotypic identification. Further research on A. neuii subsp. anitratus infections is required to avoid delayed or missed diagnoses

A case of bloodstream infection caused by Ruminococcus gnavus without gastrointestinal involvement

We report a case of bloodstream infection due to Ruminococcus gnavus (R. gnavus) associated with pelvic abscess in a 74-year-old female patient undergoing radiotherapy for cervical cancer. Gram staining of positive anaerobic blood cultures revealed short chains of gram-positive cocci. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed directly on the blood culture bottle, and 16S rRNA sequencing identified the bacterium as R. gnavus. There was no leakage from the sigmoid colon to rectum on enterography, and R. gnavus was not found in the culture of her pelvic abscess. After the administration of piperacillin/tazobactam, her condition markedly improved. This patient with R. gnavus infection demonstrated no gastrointestinal involvement, whereas past published cases reported diverticulitis or intestinal damage. It is possible that bacterial translocation of R. gnavus occurred from the gut microbiota, due to damage to the intestinal tract caused by radiation