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AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2020年第10期75卷 2760-2768页

作者： Chan, Agnes P. Choi, Yongwook Clarke, Thomas H. Brinkac, Lauren M. White, Richard C. Jacobs, Michael R. Bonomo, Robert A. Adams, Mark D. Fouts, Derrick E. J Craig Venter Inst Rockville MD 20850 USA Case Western Reserve Univ Univ Hosp Cleveland Dept Pathol Med Ctr Cleveland OH 44106 USA Case Western Reserve Univ Dept Pathol Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Med Cleveland OH 44106 USA Louis Stokes Cleveland Dept Vet Affairs Med Ctr Cleveland OH USA Case Western Reserve Univ Sch Med Dept Mol Biol & Microbiol Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Pharmacol Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Biochem Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Dept Prote & Bioinformat Cleveland OH USA CWRU Cleveland VAMC Ctr Antimicrobial Resistance Cleveland OH USA Jackson Lab Genom Med Farmington CT USA Translat Genom Res Inst Phoenix AZ USA Noblis Reston VA USA Booz Allen Hamilton Bethesda MD USA

Objectives: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates. Methods: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target. Results: Genomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8kb, bounded by IS26 at both ends, and embedded in a new target location between an alpha/beta-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene. Conclusions: A novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone.

关键词： plasmids antibiotic resistance bacterial chromosomes genes genome hydrolase oxidoreductase spectinomycin streptomycin tobramycin acinetobacter baumannii integrons naming function transfer technique resistance genes basic local alignment search tool il1rl1 gene

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Prevalence of Tinnitus and Association with Self-Rated Health among Military Personnel Injured on Combat Deployment

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MILITARY MEDICINE 2020年第9-10期185卷 E1608-E1614页

作者： MacGregor, Andrew J. Joseph, Antony R. Dougherty, Amber L. Naval Hlth Res Ctr Med Modeling Simulat & Mission Support Dept San Diego CA 92106 USA Illinois State Univ Commun Sci & Disorders Dept Hearing Loss Prevent Lab Normal IL 61761 USA Leidos Inc San Diego CA 92106 USA

Introduction Tinnitus is an auditory problem frequently reported by military personnel and is currently responsible for 1 billion dollars annually in disability compensation. Recent military conflicts in Iraq and Afghanistan saw high levels of combat exposure coupled with a surge in blast weaponry, both of which can adversely affect hearing. The present study explored the prevalence of tinnitus and the association with self-rated health among military personnel injured during combat deployment. Materials and Methods A total of 1,026 U.S. military personnel who sustained an injury during operations (592 battle blast, 73 battle nonblast, 361 nonbattle) in Iraq were identified from clinical records. Post-Deployment Health Assessments administered at two separate points in time were used to identify self-reported tinnitus symptoms and self-rated health within 1 year of injury. Results Those with a battle blast injury had the highest prevalence of tinnitus with 19.1% and 31.3% on the first and second health assessments, respectively. In a multivariate model adjusting for combat exposure, concussion, posttraumatic stress disorder, and other covariates, tinnitus was associated with lower self-rated health for both the first (odds ratio [OR] = 3.31, 95% confidence interval [CI] = 2.07-5.30, P < 0.001) and second assessments (OR = 2.52, 95% CI = 1.76-3.61, P < 0.001). Conclusions Tinnitus is a common source of impairment among military personnel injured during combat deployment and is associated with poorer self-rated health. Future research should determine whether timing of assessment is linked to symptom recognition or reporting, and what interventions are best suited for ameliorating the negative impact of tinnitus.

关键词： brain concussion military personnel post-traumatic stress disorder tinnitus military deployment basic local alignment search tool combat exposure

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BLAST-QC: automated analysis of BLAST results

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ENVIRONMENTAL MICROBIOME 2020年第1期15卷 1页

作者： Torkian, Behzad Hann, Spencer Preisner, Eva Norman, R. Sean Univ South Carolina Dept Environm Hlth Sci 921 Assembly St Columbia SC 29208 USA

Background: The basic local alignment search tool (BLAST) from NCBI is the preferred utility for sequence alignment and identification for bioinformatics and genomics research. Among researchers using NCBI's BLAST software, it is well known that analyzing the results of a large BLAST search can be tedious and time-consuming. Furthermore, with the recent discussions over the effects of parameters such as '-max_target_seqs' on the BLAST heuristic search process, the use of these search options are questionable. This leaves using a stand-alone parser as one of the only options of condensing these large datasets, and with few available for download online, the task is left to the researcher to create a specialized piece of software anytime they need to analyze BLAST results. The need for a streamlined and fast script that solves these issues and can be easily implemented into a variety of bioinformatics and genomics workflows was the initial motivation for developing this software. Results: In this study, we demonstrate the effectiveness of BLAST-QC for analysis of BLAST results and its desirability over the other available options. Applying genetic sequence data from our bioinformatic workflows, we establish BLAST_QC's superior runtime when compared to existing parsers developed with commonly used BioPerl and BioPython modules, as well as C and Java implementations of the BLAST_QC program. We discuss the 'max_target_ seqs' parameter, the usage of and controversy around the use of the parameter, and offer a solution by demonstrating the ability of our software to provide the functionality this parameter was assumed to produce, as well as a variety of other parsing options. Executions of the script on example datasets are given, demonstrating the implemented functionality and providing test-cases of the program. BLAST-QC is designed to be integrated into existing software, and we establish its effectiveness as a module of workflows or other processes. Conclusions: BLAST-

关键词： basic local alignment search tool Blast Bioinformatics Genomics Sequencing

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Case Study of a Breacher: Investigation of Neurotrauma Biomarker Levels, Self-reported Symptoms, and Functional MRI Analysis Before and After Exposure to Measured Low-Level Blast

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MILITARY MEDICINE 2020年第3-4期185卷 E513-E517页

作者： Eonta, Stephanie E. Kamimori, Gary H. Wang, Kevin K. W. Carr, Walter LaValle, Christina R. Egnoto, Michael J. Tate, Charmaine M. Walter Reed Army Inst Res 503 Robert Grant Ave Silver Spring MD 20910 USA Univ Florida McKnight Brain Inst Dept Psychiat Ctr Neuroprote & Biomarker Res 1149 South Newell Dr Gainesville FL 32611 USA Geneva Fdn 917 Pacific Ave Tacoma WA 98402 USA New Zealand Def Force 143 Porchester Rd Auckland 2110 New Zealand

We report a case study on a single military member who received moderate blast overpressure (OP) exposure during routine breacher training. We extend previous research on blast exposure during training, which lacked sufficient data to assess symptom profiles and OP exposure. The present work was conducted because a subjective symptom profile similar to that seen in sports concussion has been reported by military personnel exposed to blast. Data collection for this study was carried out under a research protocol approved by the relevant Human Subjects Review Committees on one subject, who received the highest OP exposure during training. The volunteer was a 20-year-old male with no prior history of traumatic brain injury (TBI) or blast exposure. The volunteer was part of a breacher training team that completed a 2-week explosive entry course. The course included 3 classroom days and 9 days of practical training, held in the morning, afternoon, and evening sessions. Blast exposure occurred on five of the nine practical training days, with multiple exposures over the course of each day. Assessments of serum, self-reported symptoms, magnetic resonance imaging, and blast characterization were conducted. Results indicated changes in glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 postblast exposure but did not manifest changes in spectrin-derived breakdown product 150 or magnetic resonance imaging. No additional symptoms were reported by the subject. Objective markers of mild TBI remain elusive, but support for serum biomarkers as an early detection mechanism is promising. Additionally, this case study demonstrated an association between OP and high level of neurotrauma biomarker in an individual.

关键词： magnetic resonance imaging biological markers glial fibrillary acidic protein nervous system trauma functional magnetic resonance imaging basic local alignment search tool self-report

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Blast Exposure and Risk of Recurrent Occupational Overpressure Exposure Predict Deployment TBIs

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MILITARY MEDICINE 2020年第5-6期185卷 E538-E544页

作者： Belding, Jennifer N. Fitzmaurice, Shannon Englert, Robyn Martin Lee, Isabell Kowitz, Brad Highfill-McRoy, Robyn M. Thomsen, Cynthia J. da Silva, Uade Naval Hlth Res Ctr Hlth & Behav Sci Dept 140 Sylvester Rd San Diego CA 92106 USA Leidos 10260 Campus Point Dr San Diego CA 92121 USA Naval Med Ctr San Diego Prevent Med Dept San Diego CA USA

Introduction Traumatic brain injury (TBI) has been the leading cause of morbidity and mortality in recent military conflicts and deployment-related TBIs are most commonly caused by blast. However, knowledge of risk factors that increase susceptibility to TBI following an acute, high-level blast is limited. We hypothesized that recurrent occupational overpressure exposure (ROPE) may be one factor that increases susceptibility to mild TBI (mTBI) following blast. Materials and Methods Using military occupational specialty as a proxy, we examined the effects of high versus low ROPE on mTBI following blast exposure. Initial analyses included 111,641 active-duty-enlisted U.S. Marines who completed the 2003 or 2008 version of the Post-Deployment Health Assessment. Final analyses examined probable mTBI screens among Marines with at least one qualifying exposure as a function of whether the exposure was a blast and level of ROPE (N = 12,929). This study was approved by the Institutional Review Board at the Naval Health Research Center. Results Blast and ROPE were both independently and jointly associated with a probable mTBI. Marines who experienced a blast (vs other qualifying exposure) and those in high (vs low) risk occupations were 1.07 and 1.23 times more likely to sustain a probable mTBI, respectively. Furthermore, among those who experienced a blast during deployment, those in high-risk occupations were 1.45 times more likely than those in low-risk occupations to sustain a probable mTBI. Conclusions Blast exposure and ROPE were independently associated with mTBIs, and Marines with both blast exposure during deployment and ROPE were especially likely to sustain an mTBI. This suggests that ROPE heightens the risk of mTBI following blast. Ongoing research is examining the severity, symptomology, and sequelae of TBIs as a function of ROPE.

关键词： traumatic brain injuries military personnel military deployment traumatic brain injury mild basic local alignment search tool

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Identification of Proteus genomic island 2 variants in two clonal Proteus mirabilis isolates with coexistence of a novel genomic resistance island PmGRI1

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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 2020年第9期75卷 2503-2507页

作者： Lei, Chang-Wei Yao, Tian-Ge Yan, Jia Li, Bo-Yang Wang, Xue-Chun Zhang, Yu Gao, Yu-Feng Wang, Hong-Ning Sichuan Univ Key Lab Bioresource & Ecoenvironm Anim Dis Prevent & Food Safety Key Lab Sichuan Pr Coll Life SciMinist Educ Chengdu Peoples R China

Objectives: To characterize the MDR genomic islands (GIs) in Proteus mirabilis isolates. Methods: Two P. mirabilis strains (C55 and C74) of chicken origin were subjected to WGS (HiSeq and PacBio) and the MDR GIs were determined. Results: P. mirabilis strains C55 and C74 are clonal strains and harbour different Proteus genomic island 2 (PGI2) variants (PGI2-C55 and PGI2-C74). The MDR region of PGI2-C55 is composed of two class 1 integrons, separated by a region containing seven copies of IS26 and eight resistance genes, including bla(CTX-M-3) and fosA3. The region in PGI2-C74 is a complete In4-type class 1 integron, harbouring five gene cassettes (dfrA16, bla(CARB-2), aadA2, cmlA1 and aadA1). In addition, C55 and C74 carry an SXT/R391 integrative and conjugative element (ICEPmiJpn1), harbouring blaCMY-2, and a novel 50.46 kb genomic resistance island named PmGRI1-C55. PmGRI1-C55 harbours a tyrosine-type recombinase/integrase that might be responsible for the integration of PmGRI1-C55 at the 3' end of tRNA-Sec. It carries an MDR region derived fromTn2670 that harbours a Tn21 region and carries six resistance genes (catA1, bla(TEM-1b), aphA1a, sul2, strA and strB). Blast analysis showed diverse PmGRI1 variants in P. mirabilis and Escherichia coli strains. Conclusions: The finding of the two new PGI2 variants highlights that the homologous recombination between shared components of class 1 integrons and transposition by IS26 promote the diversity of MDR regions in PGI2. PmGRI1 is a new GI that carries various resistance genes identified in P. mirabilis and E. coli.

关键词： epoprostenol proteus chickens genes genome integrase proteus mirabilis recombination genetic transfer rna tyrosine escherichia coli integrons resistance genes basic local alignment search tool whole genome sequencing

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Hearing Damage Induced by Blast Overpressure at Mild TBI Level in a Chinchilla Model

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MILITARY MEDICINE 2020年第Sup1期185卷 248-255页

作者： Smith, Kyle D. Chen, Tao Gan, Rong Z. Univ Oklahoma Sch Aerosp & Mech Engn 865 Asp Ave Norman OK 73019 USA

Introduction The peripheral auditory system and various structures within the central auditory system are vulnerable to blast injuries, and even blast overpressure is at relatively mild traumatic brain injury (TBI) level. However, the extent of hearing loss in relation to blast number and time course of post-blast is not well understood. This study reports the progressive hearing damage measured in chinchillas after multiple blast exposures at mild TBI levels (103-138 kPa or 15-20 psi). Materials and Methods Sixteen animals (two controls) were exposed to two blasts and three blasts, respectively, in two groups with both ears plugged with foam earplugs to prevent the eardrum from rupturing. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) were measured in pre- and post-blasts. Immunohistochemical study of chinchilla brains were performed at the end of experiment. Results Results show that the ABR threshold and DPOAE level shifts in 2-blast animals were recovered after 7 days. In 3-blast animals, the ABR and DPOAE shifts remained at 26 and 23 dB, respectively after 14 days. Variation of auditory cortex damage between 2-blast and 3-blast was also observed in immunofluorescence images. Conclusions This study demonstrates that the number of blasts causing mild TBI critically affects hearing damage.

关键词： chinchilla ear fluorescent antibody technique auditory brainstem responses blast cells traumatic brain injury mild basic local alignment search tool distortion product otoacoustic emissions

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Evaluation of Blast Overpressure Exposure Effects on Concentration of Antibiotics in Mice

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MILITARY MEDICINE 2020年第Sup1期185卷 256-262页

作者： Antonic, Vlado Sajja, Venkatasivasaisujith Sousa, Jason Nguyen, Ken Alamneh, Yonas Garry, Brittany Medina-Rojas, Maria Wilder, Donna Chau Vuong Potter, Brittney Zurawski, Daniel Shearer, Jonathan Black, Chad Demons, Samandra Long, Joseph Tyner, Stuart CCCRP 722 Doughten St Ft Detrick MD 21702 USA Walter Reed Army Inst Res Wound Infect Dept 503 Robert Grant Ave Silver Spring MD 20910 USA Walter Reed Army Inst Res Ctr Mil Psychiat & Neurosci Blast Induced Neurotrauma Branch 503 Robert Grant Ave Silver Spring MD 20910 USA Walter Reed Army Inst Res Expt Therapeut Branch 503 Robert Grant Ave Silver Spring MD 20910 USA

Objective Infection as sequelae to explosion-related injury is an enduring threat to our troops. There are limited data on the effects of blast on antibiotic pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. The observational study presented here is our Institute's first attempt to address this issue by combining our existing interdepartmental blast, infection modeling, and in vivo PK/PD capabilities and was designed to determine the PK effects of blast on the first-line antibiotic, cefazolin, in an in vivo mouse model. Methods A total of 160 male BALB/c mice were divided to sham and blast (exposed to blast overpressure of 19 psi) in two biological replicates. At 1 hour after blast/sham exposure, the animals received IV injection of cefazolin (328 mg/kg). Animals were euthanized at 3 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, or 10 hours after the injection. Plasma and liver were analyzed for concentration of cefazolin using mass-spectrometry. Results We observed increases in the concentration of cefazolin in the plasma and liver of blast exposed animals at later time points and increase in elimination half-life. Conclusion Our results indicate that blast-induced physiologic changes significantly influence cefazolin PK and suggest that efficacy could be affected in the context of the blast;assessment of efficacy and PD effects require further investigation. Metabolic changes resulting from blast may influence other classes of antibiotics and other therapeutics used with these injuries. Therefore, this may have important treatment considerations in other areas of military medicine.

关键词： antibiotics cefazolin plasma liver mice basic local alignment search tool

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Plasmalogens - Ubiquitous molecules occurring widely, from anaerobic bacteria to humans

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PROGRESS IN LIPID REsearch 2021年 83卷 101111-101111页

作者： Vitova, Milada Palyzova, Andrea Rezanka, Tomas Czech Acad Sci Inst Microbiol Lab Cell Cycles Algae Novohradska 237 Trebon 37981 Czech Republic Czech Acad Sci Inst Microbiol Videnska 1083 Prague 14220 Czech Republic

Plasmalogens are a group of lipids mainly found in the cell membranes. They occur in anaerobic bacteria and in some protozoa, invertebrates and vertebrates, including humans. Their occurrence in plants and fungi is controversial. They can protect cells from damage by reactive oxygen species, protect other phospholipids or lipoprotein particles against oxidative stress, and have been implicated as signaling molecules and modulators of membrane dynamics. Biosynthesis in anaerobic and aerobic organisms occurs by different pathways, and the main biosynthetic pathway in anaerobic bacteria was clarified only this year (2021). Many different analytical techniques have been used for plasmalogen analysis, some of which are detailed below. These can be divided into two groups: shotgun lipidomics, or electrospray ionization mass spectrometry in combination with high performance liquid chromatography (LC-MS). The advantages and limitations of both techniques are discussed here, using examples from anaerobic bacteria to specialized mammalian (human) organs.

关键词： ACBD acyl-CoA-binding domain APCI atmospheric pressure chemical ionization A-PE 1-alkyl-2-acyl phosphatidylethanolamine BLAST basic local alignment search tool CL cardiolipin DHAP dihydroxyacetone phosphate DRG diradylglycerol ELSD evaporative light scattering detection ESI electrospray ionization FA fatty acid PUFA polyunsaturated fatty acids FAME fatty acid methyl esters GC gas chromatography HILIC hydrophilic interaction liquid chromatography HPLC High Performance Liquid Chromatography IPTG isopropyl β-d-1-thiogalactopyranoside LC liquid chromatography MALDI matrix-assisted laser desorption ionization MHDRG monohexosyldiradylglycerol MHMAG monohexosyl monoacylglycerol MS mass spectrometry NGF nerve growth factor NPLC normal phase liquid chromatography PA phosphatidic acid P-CL 1-alkenyl-2-acyl cardiolipin PE phosphatidylethanolamine PG phosphatidylglycerol P-PC 1-alkenyl-2-acyl phosphatidylcholine P-PE 1-alkenyl-2-acyl phosphatidylethanolamine P-PS 1-alkenyl-2-acyl phosphatidylserine PS phosphatidylserine PT phosphatidylthreonine TAG triacylglyceride Q-TOF quadrupole time-of-flight RP reverse phase TLC thin layer chromatography UHPLC ultra-high-pressure liquid chromatography VAP vesicle-associated membrane protein

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Nisin-coated alginate microbeads loaded with honey-derived probiotic yeast for enhanced shelf-life and functionality in snack bars

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Carbohydrate Polymer Technologies and Applications 2025年 10卷

作者： Fatemeh Taheri Alireza Sadeghi Seid Mahdi Jafari Sara Shahryari Maryam Zarali Department of Food Science and Technology Gorgan University of Agricultural Sciences and Natural Resources Gorgan Iran Department of Food Materials and Process Design Engineering Gorgan University of Agricultural Sciences and Natural Resources Gorgan Iran

A selected yeast isolate (YI) from natural honey showed proper inhibitory activity against Bacillus cereus (77.64 %). Meanwhile, the YI had low survival under upper simulated gastrointestinal (SGI) conditions. To overcome this, YI (10 8 CFU/g) was encapsulated within dual-layered carriers of 2 % (w/v) alginate (Alg) and 4 mg/mL nisin (N). Phylogenetic evolutionary analysis led to the identification of Saccharomyces cerevisiae as the YI. The Fourier transform infrared spectroscopy and field emission scanning electron microscopy also verified the interactions between positively charged amino groups of N and negatively charged carboxylic groups of Alg and presence of N on the surface of the produced double-layer carriers. Microencapsulated yeast in double-layer Alg-N significantly ( p < 0.05) showed higher survival under SGI conditions compared to mono-layer Alg carriers (91.92 and 70.32 %, respectively), before and after application in the produced snack bar (127.31 and 89.77 %, respectively). Higher in situ inhibitory activity of the encapsulated yeast in Alg-N compared to free N against B. cereus also verified the role of N and its release during a week storage period of the product. Accordingly, dual Alg-N coated beads loaded with the YI can be sued as an efficient bio-preservation approach in the production of probiotic honey-based snack bars.

关键词： Natural honey Probiotic protective yeast Alginate-nisin microcapsule In situ antibacterial Alg alginate ANOVA one-way analysis of variance BHI brain heart infusion BLAST basic local alignment search tool CFS cell-free supernatant CFU colony forming units EE encapsulation efficiency FDA food and drug administration FESEM field emission scanning electron microscopy FTIR Fourier transform infrared GIT gastrointestinal tract HPLC high-performance liquid chromatography ITS internal transcribed spacer LAB lactic acid bacteria LbL layer-by-layer LSD least significant difference Mega molecular evolutionary genetics analysis MY microencapsulated yeast N nisin NCBI national center for biotechnology information OTA ochratoxin A PBS phosphate buffered saline PRO probiotic PTCC Persian type culture collection PYs probiotic yeasts SD standard deviation SG simulated gastric SGI simulated gastrointestinal SI simulated intestinal SUR survival YGC yeast glucose chloramphenicol YI yeast isolate YPD yeast peptone dextrose

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