Microbiological and clinical characteristics of Streptococcus pneumoniae serotype 3 infection and risk factors for severe outcome: A multicenter observational study.

BACKGROUND/PURPOSE: Serotype 3 has persisted to be an important cause of invasive pneumococcal disease in adults in the post-vaccine era. We aimed to investigate clinical and microbiological characteristics of Streptococcus pneumoniae serotype 3 infection in Taiwan and identify the risk factors associated with severe clinical outcome. METHODS: A multicenter observational study was conducted to analyze serotype 3 isolates collected between 2012 and 2021. Demographics, comorbidities, and risk categories were statistically compared with clinical outcome. Antimicrobial susceptibility testing and multilocus sequence typing were performed. RESULTS: A total of 146 isolates were collected, including 12 isolates regarded as colonizers. Among 134 infected cases, 54 (40.3%) were aged 65 and older. Mortality was significantly associated with diabetes mellitus, immunosuppression, immunodeficiency, high-risk status, and older age. Susceptibility rates were high to levofloxacin (98.9%), moxifloxacin (100%), vancomycin (100%), and ceftriaxone (97.3%). 25.3% (37/146) of the isolates showed intermediate susceptibility and 0.7% (1/146) showed resistance to penicillin. ST180 was the dominant sequence type. ST13 and ST9625 isolates were less susceptible to penicillin and ceftriaxone. CONCLUSIONS: Serotype 3 infection showed a high mortality rate, especially in patients with older ages and comorbidities. Although the incidence rates decreased during the COVID-19 pandemic, serotype 3 remained as an important cause of infection after the implementation of PCV13. Developing a more effective vaccine against serotype 3 and monitoring the antimicrobial-resistant sequence types are necessary.

Initial ecological restoration assessment of an urban river in the subtropical region in China.

Rivers in urbanised cities are often polluted, black, and odorous, with poor water quality and deteriorated ecology. Despite many river restoration studies, assessments of ecological responses to river restoration practices remain scant. Benthic animals are useful biological indicators showing the change and succession of river ecosystems; however, previous studies have mainly focussed on a few target species without considering overall ecosystem integrity. Here, we used a multi-index biological assessment method, benthic index of biological integrity (B-IBI) to assess ecological responses to river restoration of the Shahe River in subtropical region of China. Spatiotemporal changes in the macrobenthos community structure after restoration were monitored to explore species succession. We found that the number of macrobenthos species increased from 16 to 42, with the emergence of some pollution-sensitive species during the restoration period. Molluscs showed widespread recovery, and their relative proportions almost doubled from 12.5% to 24.4%. Oligochaetes and chironomids were the pioneer species in the recovering communities, while gastropod molluscs and pollution-sensitive aquatic insects were transitional species that first settled during the initial recovery period. Based on our survey data, 25 candidate metrics were selected, and five core metrics (total taxa, Simpson diversity index, percentage of crustaceans and molluscs, percentage of predators, and percentage of collector-gatherers) were identified after screening to establish the B-IBI. Our analysis revealed a distinct improvement in the overall health of the river, with the proportions of "excellent" and "good" sites increasing from zero to 28.6% and from 14.3% to 42.9%, respectively. A correlation analysis indicated that water flow, molluscs, and total phosphorus content were the three drivers of ecological recovery in the Shahe River. Overall, our study demonstrates the importance of governance and restoration of rivers in tropical and subtropical cities, and provides valuable evidence that can guide the design and evaluation of river restoration works.

Incidence rates, emerging serotypes and genotypes, and antimicrobial susceptibility of pneumococcal disease in Taiwan: A multi-center clinical microbiological study after PCV13 implementation.

Objectives The multi-center clinical microbiological study in Taiwan aimed to evaluate the impact of childhood PCV13 immunization on pneumococcal disease, and the magnitude of serotype replacement in invasive and non-invasive pneumococcal disease among all age groups. Methods The study of culture-confirmed pneumococcal disease (CCPD) was conducted at four hospitals across Taiwan in 2015-2018. Pneumococcal pneumonia was defined as clinical diagnosis with positive sputum or bronchoalveolar lavage culture. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing for penicillin and ceftriaxone were performed. Results A total of 1413 CCPD cases were identified. Invasive pneumococcal disease (IPD) accounted for 13.4% (190/1413) of CCPD. PCV7-type CCPD incidence declined among all age groups between 2015 and 2018. In adults aged 50-64 years, PCV7-type pneumococcal pneumonia incidence in 2018 was 72% lower than that in 2015, and all pneumococcal pneumonia incidence was 35% lower than that in 2015. In children, CCPD incidence was higher in 2018 than in 2015 (IRR 1.75 for age < 5 years, IRR 1.56 for age 5-17 years). Incidence of CCPD caused by non-PCV13-types, mainly 15A and 23A, increased significantly in those younger than 50 years. Serotypes 19A and 19F constituted the largest clonal complex, CC236/320 (n = 280, 19.8%). The rates of penicillin and ceftriaxone non-susceptibility were higher in PCV13-type isolates. Conclusions Childhood PCV13 immunization exerted an indirect protection to vaccine serotype clinically defined non-bacteremic pneumococcal pneumonia among adults, especially those between 50 and 64 years of age. Emerging non-PCV13 serotypes mainly caused non-invasive mucosal disease among children.

Bioavailability and trophic magnification of antibiotics in aquatic food webs of Pearl River, China: Influence of physicochemical characteristics and biotransformation.

Information on trophodynamics of antibiotics and subsequent relationships to antibiotic metabolism in river ecosystem is still unavailable, limiting the evaluation of their bioaccumulation and trophodynamics in aquatic food webs. In the present study, concentrations and relative abundance of 11 antibiotics were investigated in surface water, sediment and 22 aquatic taxa (e.g., fish, invertebrates and plankton) from Pearl River, South China. The logarithmic bioaccumulation factors (log BAFs) of antibiotics generally showed positive relationships with their log D (pH-adjusted log Kow), implying that their bioaccumulation of ionizable antibiotics depends on it is in an ionized form. Higher BAFs of antibiotics in benthic biota were observed than those in fish, indicating that sediment ingestion was a possible route of antibiotic exposure. The logarithmic biota-sediment accumulation factors (log BSAFs) of benthic biota increased when log D increased from -4.79 to -0.01, but declined thereafter. Trophodynamics of antibiotics was investigated, and intrinsic clearance were measured in liver microsomes of Tilapia zillii (trophic level [TL]: 2.5), Anabas testudineu (TL: 3.9), and Coilia grayi (TL: 5.0). Only ciprofloxacin (CFX) showed significant trophic magnification (Trophic Magnification Factor [TMF] = 1.95), and a higher metabolism rate in lower trophic levels suggest that metabolic biotransformation play a significant role in driving biomagnification of antibiotics.

Emergence and spread in Taiwan of multidrug-resistant serotypes of nontyphoidal Salmonella.

PURPOSE: Antimicrobial resistance of nontyphoidal Salmonella (NTS) is a threat to public health worldwide. METHODS: A study on longitudinally collected NTS isolates from a medical center in Taiwan from 2011 to 2019 was undertaken. The multidrug resistance (MDR) and extensively drug resistance (XDR) phenotypes were determined according to internationally used definitions. Molecular serotyping was performed on the resistant NTS. RESULTS: Notably 16.1% (870/5412) of the isolates were MDR, while XDR accounted for 2.1% (111/5412). Both MDR and XDR NTS have increased significantly from 2011 to 2019, especially from 2015 to 2017 (MDR from 9.6% in 2015 to 23.1% 2017; XDR from 1.4% in 2016 to 4.7% in 2017). S. Anatum was the commonest NTS serotype expressing MDR and XDR, in 256/559 (45.8%) and 81/111 (73.0%) of the isolates, respectively, followed by S. Typhimurium and S. Goldcoast. Children < 18 years old contributed to 69.0% of all MDR cases and 64.0% of all XDR cases; majority of them aged less than 5 years. CONCLUSIONS: Increasing MDR and XDR NTS is a threat to public health. MDR and XDR NTS usually caused gastroenteritis in children < 5 years old. Multiple NTS serotypes expressing MDR and XDR indicate multiple food vehicles involved in the transmission. Proper food hygiene practice should never be over-reinforced.

Microbiological and genomic investigations of invasive Salmonella enterica serovar Panama from a large outbreak in Taiwan.

BACKGROUND/PURPOSE: Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS: Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS: Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P = 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium. CONCLUSION: This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes.

Characterization and Source Investigation of Multidrug-Resistant Salmonella Anatum from a Sustained Outbreak, Taiwan.

An ongoing outbreak of multidrug-resistant Salmonella enterica serovar Anatum began in Taiwan in 2015. Pork and poultry were identified as vehicles for transmission. Contaminated meat contributed to the high rate of infections among children. Nearly identical Salmonella Anatum strains have been identified in the United Kingdom, the United States, and the Philippines.

Stable isotopes reveal effects of natural drivers and anthropogenic pressures on isotopic niches of invertebrate communities in a large subtropical river of China.

Isotopic niches reflect the basic structure and functioning of river food webs; however, their response to riverine environments remains unclear. We used stable isotope analysis and community-wide metrics to quantify how invertebrate niches vary with environmental changes along a large subtropical river in China. Eight niche metrics, which had higher values in the wet than in the dry season, increased from headwaters to the middle river and decreased sharply near the estuarine industrial zones. The δ13C value of > - 23.8‰, which indicated consumption of epilithic diatoms, separated the invertebrates between the upper and mid-lower reaches. The δ15N values > 9.4‰ identified site-specific nitrogen sources from manure (e.g., animal effluent) and domestic sewage in agricultural area. The output of mixing models showed a downstream shift in carbon utilization by invertebrates from autochthonous periphyton and submerged hydrophytes to allochthonous C3 plants. Principle component (PC) and cluster analysis decomposed and grouped 40 environmental variables into 4 PCs that explained 84.5% of the total variance. Hierarchical partitioning revealed that the second and first PCs, which were driven mainly by biological indicators and habitat characteristics, had the highest explanatory power for niche ranges and areas (e.g., Bayesian ellipse), respectively. Our results suggest that reducing anthropogenic pressures (e.g., habitat loss and water pollution) on river ecosystems through measures, such as protecting diatom-dominated biofilms in riffles and controlling nitrogen loading in rural regions, may produce the greatest impact for river management. Graphical abstract.

Persistence of immunity in children immunised with 13-valent pneumococcal conjugate vaccine and impact on nasopharyngeal carriage: a cross-sectional study.

In 500 children aged ≤10 years after 13-valent pneumococcal conjugate vaccine (PCV)13 immunisation in different schedules, serotypes 19A-specific and 19F-specific immunoglobulin G (IgG) were predicted to persist above 0.35 µg/mL for ≥10 years in all groups, likely due to PCV13-induced memory with natural boosting from residual diseases and colonisation. Generally, serotype-specific IgG could persist above 0.35 µg/mL longer (≥5 years) in the catch-up group than in the 2+1 and 3+1 immunisation groups. 14.5% of the carriage isolates belonged to PCV13 serotypes; statistical analysis revealed that a high serum IgG level (>10.96 µg/mL) will be required to eliminate the point-prevalence nasopharyngeal carriage of serotype 19A.

Highly antimicrobial-resistant Nontyphoidal Salmonella from retail meats and clinical impact in children, Taiwan.

BACKGROUND: The epidemiology of nontyphoidal Salmonella (NTS) resistant to ciprofloxacin or ceftriaxone and its impact on patients' clinical course are rarely reported. METHODS: Children with culture-proven salmonellosis treated in a medical center in northern Taiwan in 2017 were enrolled. To trace the source of Salmonella, Salmonella isolated from food samples were collected from markets. Antimicrobial susceptibility and serotypes were determined. RESULTS: Among the 453 isolates, 122 (26.9%) were highly antimicrobial-resistant, as defined by resistance to ciprofloxacin or ceftriaxone or both. The most prevalent highly resistant serotype was S. Anatum (66, 54.1%). Salmonella was detected in 94.1%, 66.7%, and 8.6% of examined pork, chicken, and vegetables examined, respectively. S. Anatum (6, 21.4%) and S. Derby (6, 21.4%) were the major serotypes isolated. Majority of the S. Anatum (5, 83.3%) were highly antimicrobial-resistant. More patients infected by highly resistant Salmonella required carbapenem treatment (OR = 23.5, 95% confidence interval [CI] 2.8-192.7, P < 0.001). Patients with ceftriaxone-resistant NTS infections had a significantly longer hospital stay than others (P < 0.001). Totally, 34 (7.5%) presented with invasive diseases (31 bacteremia, 1 intestinal perforation, 1 toxic megacolon and 1 septic arthritis). Risk factors for invasive disease included prolonged fever for ≧5 days and infection occurring in warmer season from May to October. The rise of ambient temperature in northern Taiwan was associated with increasing Salmonella infections. CONCLUSIONS: Retail meats were the main source of highly antimicrobial-resistant NTS in northern Taiwan. Highly antimicrobial resistance significantly impacted the clinical course and treatment of children with NTS infection.

Genomic Insight into the Spread of Meropenem-Resistant Streptococcus pneumoniae Spain23F-ST81, Taiwan.

Incidence of invasive pneumococcal disease caused by antimicrobial-resistant Streptococcus pneumoniae types not included in pneumococcal conjugate vaccines has increased, including a penicillin- and meropenem-resistant serotype 15A-ST63 clone in Japan. During 2013-2017, we collected 206 invasive pneumococcal isolates in Taiwan for penicillin and meropenem susceptibility testing. We found serotypes 15B/C-ST83 and 15A-ST63 were the most prevalent penicillin- and meropenem-resistant clones. A transformation study confirmed that penicillin-binding protein (PBP) 2b was the primary meropenem resistance determinant, and PBP1a was essential for high-level resistance. The rate of serotype 15B/C-ST83 increased during the study. All 15B/C-ST83 isolates showed an ermB macrolide resistance genotype. Prediction analysis of recombination sites revealed 12 recombination regions in 15B/C-ST83 compared with the S. pneumoniae Spain23F-ST81 genome. Pneumococcal clones rapidly recombine to acquire survival advantages and undergo local expansion under the selective pressure exerted by vaccines and antimicrobial drugs. The spread of 15B/C-ST83 is alarming for countries with high antimicrobial pressure.

Non-typeable Streptococcus pneumoniae infection in a medical center in Taiwan after wide use of pneumococcal conjugate vaccine.

BACKGROUND: Streptococcus pneumoniae is one of the most common pathogens to cause mucosal and invasive infection in humans. Most of the infection could be prevented through immunization by vaccines containing capsular polysaccharides but some infection may be caused by unencapsulated strains. METHODS: Clinical isolates of S.pneumoniae from January 2012 to December 2015 at Chang Gung Memorial Hospital, Taiwan. Serotyping by PCR method was performed. Clinical and laboratory information of patients infected by non-typeable pneumococci (NTP) were collected and analyzed. RESULTS: During the study period, 39 NTP isolates were identified. Most (21 of 39, 53.9%) were collected from purulent upper respiratory tract secretion. Others were from corneal abscess, sputum, and one from blood of a newborn. We recorded a 3.6-fold increase in the rate of isolation from 1.4% in 2012 to 5.0% in 2015 (p = 0.063). Co-infection was found in 24 cases; the major co-infecting pathogens included non-typeable Hemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Most (39 of 40, 97.5%) of the isolates were susceptible to both penicillin and ceftriaxone. The dominant sequence type ST1106 and an emerging sequence type ST7502 were recognized. CONCLUSIONS: A gradual increase of NTP infection was found in northern Taiwan in the pneumococcal conjugate vaccine era. Non-typeable pneumococci can cause respiratory and ophthalmological mucosal infection. Invasive infection can occur in newborns or young infants. Most of the isolates remained susceptible to penicillin and ceftriaxone.

Genetic analysis of virulence and antimicrobial-resistant plasmid pOU7519 in Salmonella enterica serovar Choleraesuis.

BACKGROUND: Zoonotic Salmonella enterica serovar Choleraesuis (S. Choleraesuis), causing paratyphoid in pigs and bacteremia in humans, commonly carry a virulence plasmid and sometimes a separate antimicrobial-resistant plasmid or merging together. This study aimed to analyze the likely mechanism of how to form a virulence-resistance chimera of plasmid in S. Choleraesuis. METHODS: Whole plasmid sequence of pOU7519 in S. Choleraesuis strain OU7519 was determined using shotgun cloning and sequencing. Sequence annotation and comparison were performed to determine the sequence responsible for the formation of a chimeric virulence-resistance pOU7519. Other chimeric plasmids among the collected strains of S. Choleraesuis were also confirmed. RESULTS: The sequence of pOU719, 127,212 bp long, was identified to be a chimera of the virulence plasmid pSCV50 and a multidrug-resistant plasmid pSC138 that have been found in S. Choleraesuis strain SC-B67. The pOU7519 is a conjugative plasmid carrying various mobile DNAs, including prophages, insertion sequences, integrons and transposons, especially a Tn6088-like transposon. By dissecting the junction site of the pSCV50-pSC138 chimera in pOU7519, defective sequences at integrase gene scv50 (int) and its attachment site (att) were found, and that likely resulted in a stable chimera plasmid due to the failure of excision from the pSCV50-pSC138 chimera. Similar structure of chimera was also found in other large plasmids. CONCLUSION: The deletion of both the int and att sties could likely block chimera excision, and result in an irreversible, stable pSCV50-pSC138 chimera. The emergence of conjugative virulence and antimicrobial-resistant plasmids in S. Choleraesuis could pose a threat to health public.

Evaluation of factors influencing annual occurrence, bioaccumulation, and biomagnification of antibiotics in planktonic food webs of a large subtropical river in South China.

Biological pump is important to control the fate and distribution of organic contaminants, particularly in temperate and cold oligotrophic waters. However, it remains largely unknown how factors affect the long-term occurrence and fate of ionogenic organic compounds in subtropical eutrophic waters. The present study aimed to assess biogeochemical and physical factors affecting the annual occurrence, bioaccumulation, and trophic transfer of 14 antibiotics through planktonic food webs in the Pearl River, a large subtropical eutrophic river in China. This was done by carrying out 1-year simultaneous field observations of antibiotic concentrations in five water column compartments and assessing the variability of bioconcentration (BCF), bioaccumulation (BAF), and biomagnification (BMF) factors, which were influenced by plankton biomass, pH and temperature of water columns. The annual mean antibiotic concentration per site ranged from 1014.66 ±â€¯535.66 ng L-1 to 1464.63 ±â€¯1075.91 ng L-1, and was positively correlated with phytoplankton biomass, but independent of the proximity of the sites to urban areas. Antibiotic occurrences in both phytoplankton and zooplankton were greatly influenced by a biodilution effect. The annual occurrence of antibiotics in the water column was modulated by biological pumps as well as their equilibrium partitioning, and indirectly influenced of eutrophication with pH increased with phytoplankton biomass and phytoplankton life cycling. BAF of antibiotics by plankton had biphasic correlations with temperature (n = 150, R2 = 0.17-0.60, p < 0.001) and decreased with plankton biomass (n = 105-147, R2 = 0.10-0.22, p < 0.001). The trophic transfer of antibiotics from phytoplankton to zooplankton (BMFs) were positively correlated with both phytoplankton biomass (n = 30, R2 = 0.58, p < 0.001) and temperature (n = 132-150, R2 = 0.12-0.43, p < 0.001). Mean BMFs of ciprofloxacin, lomefloxacin, ofloxacin, oxytetracycline, and tetracycline ranged between 0.18 and 2.25, implying these chemicals can undergo biomagnification along planktonic food webs. The present research demonstrates the important role of biogeochemical and physical factors in the environmental fate of antibiotics at large spatiotemporal scales.

Emergence and Evolution of High-Level Cephalosporin-Resistant Salmonella Goldcoast in Northern Taiwan.

BACKGROUND: Nontyphoidal Salmonella (NTS) is an important foodborne pathogen worldwide. We investigated a 2018 outbreak of highly antimicrobial-resistant Salmonella enterica serotype Goldcoast in northern Taiwan. METHODS: We collected 30 clinical isolates and 2 meat isolates from this outbreak in New Taipei and Taoyuan, Taiwan in 2018. The clinical manifestations and the treatment of the patients were reviewed. To trace the source, we examined NTS isolated from food samples collected from the markets in northern Taiwan. All of the isolates along with an additional human isolate from China were sequenced and compared with the sequences of Salmonella Goldcoast reported by other countries. RESULTS: The outbreak involved 14 pediatric patients (<5 years old) and 16 adults (36 to 83 years old). Nine patients with invasive or severe disease required carbapenem treatment. The MIC90 of ceftriaxone and ciprofloxacin for the outbreak isolates was >256 µg/mL and 1 µg/mL, respectively, and a conjugative 278-kilobase plasmid harboring bla CTX-M-55 and qnrS1 contributed towards the resistance. Whole-genome sequencing revealed a clonal relationship among the outbreak isolates and the 2 collected from the retail meats. The outbreak clone was phylogenetically close to that of Salmonella Goldcoast reported in the United Kingdom, Poland, and China, whereas similar resistance plasmids were found in China and Cambodia. CONCLUSIONS: The clinical spectrum of the high-level cephalosporin-resistant Salmonella Goldcoast is similar to that of other NTS serotypes, but severe cases required carbapenem treatment. The study confirmed the emergence of a highly antimicrobial-resistant clone of Salmonella Goldcoast, highlighting the importance of surveillance for food safety.

Transcription Factor Atf1 Regulates Expression of Cellulase and Xylanase Genes during Solid-State Fermentation of Ascomycetes.

Transcriptional regulation of cellulolytic and xylolytic genes in ascomycete fungi is controlled by specific carbon sources in different external environments. Here, comparative transcriptomic analyses of Penicillium oxalicum grown on wheat bran (WB), WB plus rice straw (WR), or WB plus Avicel (WA) as the sole carbon source under solid-state fermentation (SSF) revealed that most of the differentially expressed genes (DEGs) were involved in metabolism, specifically, carbohydrate metabolism. Of the DEGs, the basic core carbohydrate-active enzyme-encoding genes which responded to the plant biomass resources were identified in P. oxalicum, and their transcriptional levels changed to various extents depending on the different carbon sources. Moreover, this study found that three deletion mutants of genes encoding putative transcription factors showed significant alterations in filter paper cellulase production compared with that of a parental P. oxalicum strain with a deletion of Ku70 (ΔPoxKu70 strain) when grown on WR under SSF. Importantly, the ΔPoxAtf1 mutant (with a deletion of P. oxalicumAtf1, also called POX03016) displayed 46.1 to 183.2% more cellulase and xylanase production than a ΔPoxKu70 mutant after 2 days of growth on WR. RNA sequencing and quantitative reverse transcription-PCR revealed that PoxAtf1 dynamically regulated the expression of major cellulase and xylanase genes under SSF. PoxAtf1 bound to the promoter regions of the key cellulase and xylanase genes in vitro This study provides novel insights into the regulatory mechanism of fungal cellulase and xylanase gene expression under SSF.IMPORTANCE The transition to a more environmentally friendly economy encourages studies involving the high-value-added utilization of lignocellulosic biomass. Solid-state fermentation (SSF), that simulates the natural habitat of soil microorganisms, is used for a variety of applications such as biomass biorefinery. Prior to the current study, our understanding of genome-wide gene expression and of the regulation of gene expression of lignocellulose-degrading enzymes in ascomycete fungi during SSF was limited. Here, we employed RNA sequencing and genetic analyses to investigate transcriptomes of Penicillium oxalicum strain EU2101 cultured on medium containing different carbon sources and to identify and characterize transcription factors for regulating the expression of cellulase and xylanase genes during SSF. The results generated will provide novel insights into genetic engineering of filamentous fungi to further increase enzyme production.

VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer1,2. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies3. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood. Here we report that V-domain immunoglobulin suppressor of T cell activation (VISTA) engages and suppresses T cells selectively at acidic pH such as that found in tumour microenvironments. Multiple histidine residues along the rim of the VISTA extracellular domain mediate binding to the adhesion and co-inhibitory receptor P-selectin glycoprotein ligand-1 (PSGL-1). Antibodies engineered to selectively bind and block this interaction in acidic environments were sufficient to reverse VISTA-mediated immune suppression in vivo. These findings identify a mechanism by which VISTA may engender resistance to anti-tumour immune responses, as well as an unexpectedly determinative role for pH in immune co-receptor engagement.

Evaluation of the impact of 13-valent pneumococcal conjugate vaccine immunization in children by surveillance of culture-confirmed pneumococcal disease: A prospective clinical microbiological study.

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST6315A, ST8315B, and ST166/33823A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.