Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection.

To restrict infection by Legionella pneumophila, mouse macrophages require Naip5, a member of the nucleotide-binding oligomerization domain leucine-rich repeat family of pattern recognition receptors, which detect cytoplasmic microbial products. We report that mouse macrophages restricted L. pneumophila replication and initiated a proinflammatory program of cell death when flagellin contaminated their cytosol. Nuclear condensation, membrane permeability, and interleukin-1beta secretion were triggered by type IV secretion-competent bacteria that encode flagellin. The macrophage response to L. pneumophila was independent of Toll-like receptor signaling but correlated with Naip5 function and required caspase 1 activity. The L. pneumophila type IV secretion system provided only pore-forming activity because listeriolysin O of Listeria monocytogenes could substitute for its contribution. Flagellin monomers appeared to trigger the macrophage response from perforated phagosomes: once heated to disassemble filaments, flagellin triggered cell death but native flagellar preparations did not. Flagellin made L. pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages restricted the growth of virulent microbes, but flagellin mutants replicated freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L. pneumophila in the lungs declined, whereas the burden of flagellin mutants increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism that requires Naip5 and caspase 1 to restrict bacterial replication and release proinflammatory cytokines that control L. pneumophila infection

Evaluation of the antimicrobial activity of ridinilazole and six comparators against Chinese, Japanese and South Korean strains of Clostridioides difficile

BACKGROUND: Clostridioides difficile is the most common cause of antimicrobial-associated diarrhoea in high-income countries. Fluoroquinolone resistance enabled the emergence and intercontinental spread of the epidemic ribotype (RT) 027 strain of C. difficile in the early 2000s. Despite frequent inappropriate antimicrobial use in Asia, RT 027 is rarely isolated in the region, but the often fluoroquinolone- and clindamycin-resistant RT 017 strain predominates. OBJECTIVES: This study evaluated the antimicrobial activity of ridinilazole, a novel antimicrobial agent with highly specific activity for C. difficile, against clinical strains of C. difficile from Asia. METHODS: C. difficile strains from Japan (n = 64), South Korea (n = 32) and China (n = 44) were tested by the agar dilution method for susceptibility to ridinilazole, metronidazole, vancomycin, clindamycin, moxifloxacin, rifaximin and fidaxomicin. RESULTS: All strains were susceptible to ridinilazole, with low MICs (0.03-0.25 mg/L). Several strains showed multiresistance profiles, particularly RT 017 (100% clindamycin resistant, 91.3% moxifloxacin resistant, 82.6% rifaximin resistant) and RT 369 (94.4% clindamycin resistant, 100% moxifloxacin resistant). Rifaximin resistance was absent in all strains from Japan. Multiresistance to clindamycin, moxifloxacin and rifaximin was found in 19 RT 017 strains (from China and South Korea), 2 RT 001 strains (South Korea) and 1 RT 046 strain (South Korea). CONCLUSIONS: Ridinilazole showed potent activity against a range of Asian C. difficile strains, which otherwise frequently displayed resistance to several comparator antimicrobial agents. Ongoing surveillance of antimicrobial resistance profiles is required to monitor and control the spread of resistant strains

Reconstruction of radiocesium levels in sediment off Fukushima: Simulation analysis of bioavailability using parameters derived from observed 137Cs concentrations

Radiocesium was released to the North Pacific coastal waters by the accident at the Fukushima Dai-ichi Nuclear Power Plant (1FNPP) of the Tokyo Electric Power Company (TEPCO) in March 2011. Since the radiocesium in the sediment off Fukushima was suggested as a possible source for the transfer of this radionuclide through the benthic food chain, we conducted numerical simulations of 137Cs in sediments off the Fukushima coast by using a model which incorporates dynamic transfer processes between seawater and the labile and refractory fractions in sediment particles. This model reproduced the measured temporal changes of 137Cs concentration in seabed surface sediment off Fukusima coasts, by normalizing the radiocsium transfer between seawater and sediment according to the particle diameter sizes. We found that the 137Cs level in sediment decreased by desorption during the first several months after the accident, followed by a reduction in the labile fraction until the end of 2012. The apparent decrease of the total radiocesium level in surface sediment was estimated to occur at rates of approximately 0.2 y−1 within a 20 km distance from the 1FNPP. The comparison of 137Cs level decreases in the demersal fish and the simulated temporal labile fraction in fine sediment demonstrated that the consideration of radiocesium transfer via sediment is important for determining the 137Cs depuration mechanism in some demersal fish

Impacts of direct release and river discharge on oceanic 137Cs derived from the Fukushima Dai-ichi Nuclear Power Plant accident

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the Great East Japan Earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean. We used the Regional Ocean Model System (ROMS) to simulate the 137Cs activity in the oceanic area off Fukushima, with the sources of radioactivity being direct release, atmospheric deposition, river discharge, and inflow across the domain boundary. The direct release rate of 137Cs after the accident until the end of 2016 was estimated by comparing simulated results with measured 137Cs activities adjacent to the 1F NPP. River discharge rates of 137Cs were estimated by multiplying simulated river flow rates by the dissolved 137Cs activities, which were estimated by an empirical function. Inflow of 137Cs across the domain boundary was set according to the results of a North Pacific Ocean model. Because the spatiotemporal variability of 137Cs activity was large, the simulated results were compared with the annual averaged observed 137Cs activity distribution. Normalized annual averaged 137Cs activity distributions in the regional ocean were similar for each year from 2013 to 2016. This result suggests that the annual averaged distribution is predictable. Simulated 137Cs activity attributable to direct release was in good agreement with measurement data from the coastal zone adjacent to the 1F NPP. Comparison of the simulated results with measured activity in the offshore area indicated that the simulation slightly underestimated the activity attributable to inflow across the domain boundary. This result suggests that recirculation of subducted 137Cs to the surface layer was underestimated by the North Pacific model. During the study period, the effect of river discharge on oceanic 137Cs activity was small compared to the effect of directly released 137Cs

Evolutionary and genomic insights into Clostridioides difficile sequence type 11: A diverse zoonotic and antimicrobial-resistant lineage of global One Health importance

Clostridioides difficile (Clostridium difficile) sequence type 11 (ST11) is well established in production animal populations worldwide and contributes considerably to the global burden of C. difficile infection (CDI) in humans. Increasing evidence of shared ancestry and genetic overlap of PCR ribotype 078 (RT078), the most common ST11 sublineage, between human and animal populations suggests that CDI may be a zoonosis. We performed whole-genome sequencing (WGS) on a collection of 207 ST11 and closely related ST258 isolates of human and veterinary/environmental origin, comprising 16 RTs collected from Australia, Asia, Europe, and North America. Core genome single nucleotide variant (SNV) analysis identified multiple intraspecies and interspecies clonal groups (isolates separated by ≤2 core genome SNVs) in all the major RT sublineages: 078, 126, 127, 033, and 288. Clonal groups comprised isolates spread across different states, countries, and continents, indicative of reciprocal long-range dissemination and possible zoonotic/anthroponotic transmission. Antimicrobial resistance genotypes and phenotypes varied across host species, geographic regions, and RTs and included macrolide/lincosamide resistance (Tn6194 [ermB]), tetracycline resistance (Tn6190 [tetM] and Tn6164 [tet44]), and fluoroquinolone resistance (gyrA/B mutations), as well as numerous aminoglycoside resistance cassettes. The population was defined by a large “open” pan-genome (10,378 genes), a remarkably small core genome of 2,058 genes (only 19.8% of the gene pool), and an accessory genome containing a large and diverse collection of important prophages of the Siphoviridae and Myoviridae. This study provides novel insights into strain relatedness and genetic variability of C. difficile ST11, a lineage of global One Health importance. IMPORTANCE: Historically, Clostridioides difficile (Clostridium difficile) has been associated with life-threatening diarrhea in hospitalized patients. Increasing rates of C. difficile infection (CDI) in the community suggest exposure to C. difficile reservoirs outside the hospital, including animals, the environment, or food. C. difficile sequence type 11 (ST11) is known to infect/colonize livestock worldwide and comprises multiple ribotypes, many of which cause disease in humans, suggesting CDI may be a zoonosis. Using high-resolution genomics, we investigated the evolution and zoonotic potential of ST11 and a new closely related ST258 lineage sourced from diverse origins. We found multiple intra- and interspecies clonal transmission events in all ribotype sublineages. Clones were spread across multiple continents, often without any health care association, indicative of zoonotic/anthroponotic long-range dissemination in the community. ST11 possesses a massive pan-genome and numerous clinically important antimicrobial resistance elements and prophages, which likely contribute to the success of this globally disseminated lineage of One Health importance

Prevalence of Antimicrobial Resistance in Haemophilus influenzae and Streptococcus pneumoniae : Comparison of Clinical Isolates of Japan and The Philippines

For clinical isolates of Haemophilus influenzae and Streptococcus pneumoniae in Japan (356 and 179 strains, respectively) and in the Philippines (98 and 59 strains, respectively), minimum inhibitory concentrations (MICs) of ampicillin, cefazolin, cefotiam, ceftizoxim, ofloxacin, erythromycin, and minocycline were examined. The rates of β-lactamase producing H. influenzae were 17.7% (63/356) in Japan and 2.0% (2/98) in the Philippines, and all of these strains were ampicillin MICs 〓1.56 ugml^. In addition, 5 strains in Japan that lacked β-lactamase activity were also less susceptible to ampicillin. Among the antimicrobials tested, ceftizoxim was the most active against H. influenzae in both countries (MICs 〓0.2 ugml^). Five strains of S. pneumoniae in Japan were relatively resistant to ampicillin (MIC=0.1 ugml^), whereas there were no such strains among isolates in the Philippines. Forty strains (22.3%) and 108 strains (60.3%) among S. pneumoniae in Japan exhibited erythromycin MICs 〓0.2 ugml^ and minocycline MICs 〓1.56 ugml^, respectively. In contrast, all isolates in the Philippines were erythromycin MICs 〓0.05 ugml^ and minocycline MICs 〓0.39 ugml^. Present study indicates that H. influenzae and S. pneumoniae in the Philippines remained still susceptible to the antimicrobials tested except for 2 β-lactamase-positive, ampicillin-resistant H. influenzae, whereas ampicillin-resistant H. influenzae mediated by β-lactamase or non-β-lactamase mechanisms and ampicillin-, erythromycin- or minocycline-resistant S. pneumoniae were included among isolates in Japan

Metastatic Renal Cell Carcinoma to the Left Sphenoid Sinus: A Case Report in Light of the Literature

A 79-year-old Japanese woman presented with a rare case of metastatic renal cell carcinoma to the left sphenoid sinus with left nasal bleeding. She had previously had right radical nephrectomy for renal cell carcinoma at the age of 64 years and brain and spinal cord infarction at 74 years. Endoscopic examination revealed no mass in the nasal cavity. CT and MRI revealed a tumor in the left sphenoid sinus. The size of the tumor increased gradually from 12 to 15 years after the radical nephrectomy. Complete resection with endoscopic surgery was performed without preoperative embolization. The tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. These findings were identical to the pathological findings of the surgical specimen of the renal cell carcinoma from 15 years previous. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. PET-CT demonstrated no metastasis. The patient’s condition was successfully managed with excision of the tumor, and she remains well with no evidence of recurrence and metastasis 36 months after treatment. Metastatic renal cell carcinoma to the sphenoid sinus is rare, but it might be considered in the differential diagnosis of masses in the paranasal sinus even long after initial treatment of renal cancer

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16–40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan