Fourth Strain Research Articles

Characterizing the loss and acquisition of Tn2-like transposon in Klebsiella pneumoniae: Implications for carbapenemase gene dissemination

Over 1 year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

Carbapenem-resistant Citrobacter freundii harboring blaKPC-2 and blaNDM-1: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100.

The increase in clinical Enterobacteriaceae with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of blaKPC-2- and blaNDM-1-coharboring carbapenem-resistant Citrobacter freundii (CRCF). Four blaKPC-2- and blaNDM-1-coharboring CRCF strains were collected from our surveillance of the prevalence of carbapenem-resistant Enterobacteriaceae. The isolates were assessed using species identification, antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, plasmid stability, and fitness costs. Clonality, genome, plasmidome, and phylogeny were analyzed to reveal potential dissemination. Three ST523 blaKPC-2- and blaNDM-1-coharboring CRCF strains, collected from the same hospital within 1 month, exhibited high homology (both identity and coverage >99%), implying clonal dissemination and a small-scale outbreak. Moreover, the blaKPC-2 and blaNDM-1 genes were coharbored on an IncR plasmid, probably generated by a blaKPC-2-harboring plasmid acquiring blaNDM-1, in these three strains. Importantly, the IncR plasmid may form a transferable hybrid plasmid, mediated by IS6100 via transposition, with another IncFII plasmid included in the same C. freundii strain. Furthermore, the blaKPC-2 and blaNDM-1 of the fourth CRCF strain are located on two different non-transferable plasmids lacking complete transfer elements. Additionally, throughout the course of the 10-day continuous passage, the genetic surroundings of blaNDM-1 in four CRCF strains were gradually excised from their plasmids after the 8th day, whereas they maintained 100% retention for blaKPC-2. Genome and plasmidome analyses revealed that blaKPC-2- or blaNDM-1-harboring C. freundii were divergent, and these plasmids have high homology to plasmids of other Enterobacteriaceae. Clonal dissemination of ST523 blaKPC-2- and blaNDM-1-coharboring CRCF strains was detected, and we first reported blaKPC-2 and blaNDM-1 concomitantly located on one plasmid, which could be transferred with mediation by IS6100 via transposition. Continued surveillance should urgently be implemented.

Structure-Guided Evolution Modulate Alcohol Oxidase to Improve Ethanol Oxidation Performance.

A high ethanol usage of alcohol oxidase (AOX) was required in industry. In this study, a "expand substrate pocket" strategy achieved a high activity AOX from Hansenula polymorpha (H. polymorpha) by Phe to Val residue (F/V) site-directed mutation to enlarge ethanol channel. Although H. Polymorpha AOX (HpAOX) possessed respectively 71.3% and 76.1% similarity with AOX (PpAOX) from Pichia pastoris (P. pastoris) in DNA and protein sequences, their active site structures including catalytic site and substrate channel were similar according to computer-aided analysis. After 3D structure analysis, Phe99 residue of their substrate channels was the most important residue to impact enzyme activity because of its large aromatic side chains. F99V mutation of HpAOX (HpAOXF99V) was designed and executed based on the enzyme catalytic mechanism and molecular computation in order to allow more larger size ethanol into active site. The highest enzyme activity of the fourth strains of HpAOXF99V mutant strain exhibited 12.06-folds increase than that of the host GS115 strain. Furthermore, kinetic studies indicated that the HpAOXF99V significantly promoted catalytic efficiency of ethanol than HpAOX, including Km, Vmax, kcat and kcat/Km. We also provided a new insight that the cofactor FAD irritated both active AOX octamer biosynthesis production and enzyme-catalysed ability due to help enzyme assembly and redox potential.

Wolbachia infection dynamics in a natural population of the pear psyllid Cacopsylla pyri (Hemiptera: Psylloidea) across its seasonal generations

Wolbachia is one of the most abundant intracellular symbionts of arthropods and has profound effects on host biology. Wolbachia transmission and host phenotypes often depend on its density within the host, which can be affected by multiple biotic and abiotic factors. However, very few studies measured Wolbachia density in natural host populations. Here, we describe Wolbachia in the pear psyllid Cacopsylla pyri from three populations in the Czech Republic. Using phylogenetic analyses based on wsp and multilocus sequence typing genes, we demonstrate that C. pyri harbours three new Wolbachia strains from supergroup B. A fourth Wolbachia strain from supergroup A was also detected in parasitised immatures of C. pyri, but likely came from a hymenopteran parasitoid. To obtain insights into natural Wolbachia infection dynamics, we quantified Wolbachia in psyllid individuals from the locality with the highest prevalence across an entire year, spanning several seasonal generations of the host. All tested females were infected and Wolbachia density remained stable across the entire period, suggesting a highly efficient vertical transmission and little influence from the environment and different host generations. In contrast, we observed a tendency towards reduced Wolbachia density in males which may suggest sex-related differences in Wolbachia-psyllid interactions.

Genome Sequence of a New "Candidatus" Phylum "Dependentiae" Isolate from Chiba, Japan.

ABSTRACTLittle is known about the bacterial phylum “Candidatus Dependentiae,” because only three isolates have been reported. Here, I report the isolation and genome sequencing of a new member of this phylum, strain Noda2021. This is the fourth strain isolated from the phylum “Candidatus Dependentiae.”

Cold case: The disappearance of Egypt bee virus, a fourth distinct master strain of deformed wing virus linked to honeybee mortality in 1970’s Egypt

In 1977, a sample of diseased adult honeybees (Apis mellifera) from Egypt was found to contain large amounts of a previously unknown virus, Egypt bee virus, which was subsequently shown to be serologically related to deformed wing virus (DWV). By sequencing the original isolate, we demonstrate that Egypt bee virus is in fact a fourth unique, major variant of DWV (DWV-D): more closely related to DWV-C than to either DWV-A or DWV-B. DWV-A and DWV-B are the most common DWV variants worldwide due to their close relationship and transmission by Varroa destructor. However, we could not find any trace of DWV-D in several hundred RNA sequencing libraries from a worldwide selection of honeybee, varroa and bumblebee samples. This means that DWV-D has either become extinct, been replaced by other DWV variants better adapted to varroa-mediated transmission, or persists only in a narrow geographic or host range, isolated from common bee and beekeeping trade routes.

Comparison of survival rates in four inbred mouse strains under different housing conditions: effects of environmental enrichment.

Housing conditions can affect the well-being of laboratory animals and thereby affect the outcomes of experiments. The appropriate environment is essential for the expression of natural behavior in animals. Here, we compared survival rates in four inbred mouse strains maintained under three different environmental conditions. Three mouse strains (C57BL/6J, C3H/HeN, and DBA/2J) housed under environmental enrichment (EE) conditions showed improved survival; however, EE did not alter the survival rate of the fourth strain, BALB/c. None of the strains showed significant differences in body weights or plasma corticosterone levels in the three environmental conditions. For BALB/c mice, the rates of debility were higher in the EE group. Interestingly, for C57BL/6J and C3H/HeN mice, the incidence of animals with alopecia was significantly lower in the EE groups than in the control group. It is possible that the enriched environment provided greater opportunities for sheltering in a secure location in which to avoid interactions with other mice. The cloth mat flooring used for the EE group was bitten and chewed by the mice. Our findings suggest that depending on the mouse strains different responses to EE are caused with regard to health and survival rates. The results of this study provide basic data for further studies on EE.

Taxonomic relationship between two small-sized Chaetoceros species (Bacillariophyta): C. tenuissimus and C. salsugineus, and comparison with C. olympicus sp. nov. from Catalan coastal waters (NW Mediterranean)

ABSTRACT The majority of species of the highly diverse genus Chaetoceros are described as chain-forming, although several species are described as strictly solitary (such as C. tenuissimus) or having an alternate solitary and a chain-forming phase during their life history (such as C. salsugineus). In this study, the diversity of small forms of Chaetoceros from the NW Mediterranean coastal waters was explored through the morphological and molecular characterization of four different strains belonging to two distinct species. Based on their morphology, three of the strains were identified as C. salsugineus (Takano, 1983). The SSU and LSU rDNA sequences represented the first available for well-characterized C. salsugineus strains and were 96.6–100% similar to publicly available C. tenuissimus (Meunier, 1913) sequences. Both species share the same morphological features, such as setae and ultrastructure of the valves, as well as the rimoportula characteristics. In addition, the morphology of the solitary form of C. salsugineus matched with that of C. tenuissimus. Here, we propose the two species as synonyms (the name C. tenuissimus prevailing as it has priority for this taxon), emend the original description and designate an epitype. The fourth strain was identified as C. olympicus sp. nov., a new species, which alternates solitary and chain-forming forms within its life history. The main differential characteristics of this species are the absence of rimoportula both in terminal and intercalary valves, the setae ultrastructure, which is thin and circular in cross-section with a few, slightly twisted, rows of small rectangular poroids and some spirally arranged spines, and the morphology of the resting spores, with primary valve vaulted and covered with short to medium-sized spines, and secondary valve smaller, rounded and smooth. A comparison of C. tenuissimus and C. olympicus with other species as well as information on their life cycle and ecology is also provided. HIGHLIGHTS • Description of a new Chaetoceros species: C. olympicus. • Proposal that C. tenuissimus and C. salsugineus are synonyms. • Importance of morphological variability in life cycles for species identification.

Genetic Similarity of Staphylococcus aureus Strains Isolated from Nose and Mobile Phones of Healthcare Providers Working in the Operating Room and Intensive Care Unit

Purpose : Staphylococcus aureus colonized in the nose of healthcare workers is an important risk factor for the development of hospital-acquired staphylococcal infections. Cross-contamination of this bacterium between the hands of healthcare workers and the surfaces they contact is known. In this study, we aimed to evaluate the clonal relationship between eight S. aureus strains isolated from the nose of healthcare providers and five S. aureus strains isolated from mobile phones carried by healthcare providers. Methods: The clonal relationship between the strains and molecular epidemiological status were investigated by the pulsed-field gel electrophoresis (PFGE) method. Results : The first and third strains are isolated from the mobile phone and the nose of a healthcare provider working in the intensive care unit were the same. The second and fourth strains were isolated from the mobile phone and nose of another healthcare provider working in the intensive care unit were the same. The fifth strain, which was found to be the same as the second and fourth strains, was isolated from the mobile phone of another healthcare provider working in the intensive care unit. No similarity was observed between the other strains. Conclusion: Our findings indicate that S. aureus strains colonized in the nose of healthcare workers are also transmitted to other surfaces and that the hospital environment and co-used devices pose a risk for spread. For this reason, training of healthcare workers on the infection control procedure, hand hygiene, environmental disinfection and regular cleaning of mobile phones are important components in order to prevent hospital-acquired infections.

Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy children (6 months to 17 years of age): a randomized, multicenter, phase III clinical trial

ABSTRACT This phase III clinical trial was conducted to evaluate the immunogenicity and safety of the Tetravalent Influenza Vaccine (Split virion) I.P. (TetIV), containing two strains each of influenza A and B, developed indigenously in the country for the first time by M/s Cadila Healthcare Limited, India for use in the pediatric population (6 months −17 years of age), and compare it to that of a licensed seasonal Trivalent Influenza Vaccine (TriIV) of Sanofi Pasteur India Private Limited, containing two influenza A and one influenza B strains. Three hundred six subjects of either sex, 6 months to 17 years of age, were randomized in a 1:1 ratio to receive either TetIV or TriIV. Immunogenicity assessments (antibodies against A/H1N1, A/H3N2, B/Phuket, and B/Brisbane) were performed using the hemagglutination inhibition assay at baseline and 28 days after the last vaccination. TetIV was found to fulfill the criteria set by the United States Food and Drug Administration on the requirements of clinical data for licensure of seasonal inactivated influenza vaccines for the pediatric population. The seroconversion rates with TetIV were 94.6% for A/H1N1, 93.9% for A/H3N2, 91.2% for B/Brisbane, and 87.2% for B/Phuket strains. TetIV showed non-inferiority and superiority in immune response, as compared to TriIV, against the shared strains and an additional B strain, respectively. Both the vaccines were tolerated well by all the study participants, and an addition of the fourth strain in TetIV did not compromise the safety as compared to that of TriIV. The most common adverse event reported in both groups was fever.

Genome Sequence of a CHeRI Orbivirus 3 Strain Isolated from a Dead White-Tailed Deer (Odocoileus virginianus) in Florida, USA.

We report the genome sequence of an orbivirus isolated from a dead farmed white-tailed deer in Florida. The deer was coinfected with epizootic hemorrhagic disease virus type 2. Phylogenetic and genetic analyses supported the virus as the fourth strain of the CHeRI orbivirus 3 species.

Differences in metabolites production using the Biolog FF Microplate™ system with an emphasis on some organic acids of Aspergillus niger wild type strains

This paper investigates the differences in some metabolites using Biolog FF Microplate™ system and the production of organic acids such as β-hydroxybutyric, p-hydroxyphenylacetic, and others. Another group of organic acids such as gluconic, oxalic and citric acid were studied during cultivation in a liquid medium. Four different Aspergillus niger (An) wild type strains were used as a model organism. Three strains, from the Banska Stiavnica – Sobov (An – S), Pezinok (An – P) and Slovinky (An – Sl) localities were isolated from contaminated old mining areas with soil with ultra acidic to strong alkaline reactions. The fourth strain isolated from the Gabcikovovo (An – G) locality was used for comparative purposes. According to the RAMP analysis, the strains are clustered into two groups, An – S and An – P (similarity 82%), An – G and An – Sl (similarity 64%) which correlates with the pH values of the original environment. However, significant differences were found in metabolic processes in the reaction with a wide range of organic acids. In general, the reactions with D-lactic acid and D-malic acid correlate with the results of the RAMP analysis of fungal genotype similarities, the An – S and An – P strains had an identical negative reaction, and an identical positive reaction was found in the An – Sl and An – G strains. During incubation the wild-type strains produced substantial amounts of gluconic acid, oxalic acid and small amounts of citric acid. The appearance and accumulation of organic acids was found to be highly pH dependent with the most active strain isolated from an ultra-acidic environment. The comparative strain differs entirely in the production of oxalic acid.

Biological Characteristics and Molecular Mechanism of Fludioxonil Resistance in Botrytis cinerea From Henan Province of China.

The gray mold caused by Botrytis cinerea has a significant impact on tomato production throughout the world. Although the synthetic fungicide fludioxonil can effectively control B. cinerea, there have been several reports of resistance to this fungicide. This study indicated that all of the fludioxonil-resistant strains tested, including one field-resistant isolate and four laboratory strains, had reduced fitness relative to sensitive isolates. In addition to having reduced growth, sporulation, and pathogenicity, the resistant strains were more sensitive to osmotic stress and had significantly (P < 0.05) higher peroxidase activity. BOs1, a kinase in the high-osmolarity glycerol stress response signal transduction pathway, is believed to harbor mutations related to fludioxonil resistance. Sequence analysis of their BOs1 sequences indicated that the fludioxonil-resistant field isolate, XXtom1806, had four point mutations resulting in four amino acid changes (I365S, S531G, T565N, and T1267A) and three amino acids (I365S, S531G, and T565N) in the histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis receptors, and phosphatases domain, which associated with fludioxonil binding. Similarly, two of the laboratory strains, XXtom-Lab1 and XXtom-Lab4, had three (Q846S, I1126S, and G415D) and two (P1051S and V1241M) point mutations, respectively. A third strain, XXtom-lab3, had a 52-bp insertion that included a stop codon at amino acid 256. Interestingly, the BOs1 sequence of the fourth laboratory strain, XXtom-lab5, was identical to those of the sensitive isolates, indicating that an alternative resistance mechanism exists. The study also found evidence of positive cross-resistance between fludioxonil and the dicarboximide fungicides procymidone and iprodione, but no cross-resistance was detected with any other fungicides tested, including boscalid, carbendazim, tebuconazole, and fluazinam.

Zn isotope fractionation during uptake into marine phytoplankton: Implications for oceanic zinc isotopes

The extreme scarcity of zinc (Zn) in the euphotic zone, coupled to deep enrichments, is consistent with biological uptake at the surface and regeneration at depth. In the context of a nutrient-type depth profile so clearly shaped by uptake into phytoplankton, the growing dataset for Zn isotopes presents a challenge. These data either show very minor isotope effects associated with extreme depletion, or enrichment of the light isotopes in the upper ocean. In contrast, culturing of eukaryotes in the laboratory suggests that light Zn isotopes are preferentially taken up into diatoms and coccoliths, implying that Zn depletion at the surface should be associated with extremely heavy residual dissolved signals.Here we present the first Zn isotope measurements for cultured marine cyanobacteria and compare these data to those for eukaryotic diatoms grown under identical conditions. Of the four cyanobacteria cultured, belonging to the genera Synechococcus and Prochlorococcus, three preferentially take up light Zn into the cell, with a variability that is not fundamentally different between pro- and eukaryotic phytoplankton. We also observe only very subtle differences between Zn/P and Fe/P uptake ratios for these three cyanobacteria groups relative to diatoms grown under the same conditions. A fourth strain exhibits preferential uptake of heavy Zn isotopes, and very high Zn/P ratios. Overall, we speculate that the observed variability among cyanobacteria may be related to the molecular structure of their photosynthetic light harvesting apparatus, adapted to significantly different light niches.These new and published culture data support the hypothesis that cellular δ66Zn in culture might largely be controlled by the organic ligands that bind Zn in the medium. Given that the Zn-binding ligands in the ocean have thermodynamic stability constants that are orders of magnitude smaller than the EDTA used in culture media, the surprisingly subtle Zn isotope variability in some parts of the surface ocean may be reconciled with culture data by the lesser, near zero, preference of these weaker complexes for heavy Zn isotopes.“This article is part of a special issue entitled: “Cycles of trace elements and isotopes in the ocean - GEOTRACES and beyond” - edited by Tim M. Conway, Tristan Horner, Yves Plancherel, and Aridane G. González.”

Comparative genomic analysis of Parageobacillus thermoglucosidasius strains with distinct hydrogenogenic capacities

BackgroundThe facultatively anaerobic thermophile Parageobacillus thermoglucosidasius produces hydrogen gas (H2) by coupling CO oxidation to proton reduction in the water-gas shift (WGS) reaction via a carbon monoxide dehydrogenase–hydrogenase enzyme complex. Although little is known about the hydrogenogenic capacities of different strains of this species, these organisms offer a potentially viable process for the synthesis of this alternative energy source.ResultsThe WGS-catalyzed H2 production capacities of four distinct P. thermoglucosidasius strains were determined by cultivation and gas analysis. Three strains (DSM 2542T, DSM 2543 and DSM 6285) were hydrogenogenic, while the fourth strain (DSM 21625) was not. Furthermore, in one strain (DSM 6285) H2 production commenced earlier in the cultivation than the other hydrogenogenic strains. Comparative genomic analysis of the four strains identified extensive differences in the protein complement encoded on the genomes, some of which are postulated to contribute to the different hydrogenogenic capacities of the strains. Furthermore, polymorphisms and deletions in the CODH-NiFe hydrogenase loci may also contribute towards this variable phenotype.ConclusionsDisparities in the hydrogenogenic capacities of different P. thermoglucosidasius strains were identified, which may be correlated to variability in their global proteomes and genetic differences in their CODH-NiFe hydrogenase loci. The data from this study may contribute towards an improved understanding of WGS-catalysed hydrogenogenesis by P. thermoglucosidasius.

Novel green algal isolates from the Egyptian hyper‐arid desert oases: a polyphasic approach with a description of Pharao desertorum gen. et sp. nov. (Chlorophyceae, Chlorophyta)

The biodiversity of terrestrial algae is still grossly understudied, and African deserts in particular are barely touched in this respect. Here, four coccoid green algae from oases in the Western Desert of Egypt were characterized using a combination of morphotaxonomic, ecological and 18S rDNA data, with additional carotenoid and lipid analyses for two of the strains. Three strains were identified as affiliated with known taxa: Mychonastes sp., Asterarcys sp. (first report of this genus from a desert soil), and Stichococcus cf. deasonii. The fourth strain is proposed to represent a new cryptic genus Pharao gen. nov., with the type species P.desertorum sp. nov. The new taxon is sister to the clade of uncharacterized North American desert strains of Radiococcaceae (Chlorophyceae, Chlorophyta). The pigment profile of P.desertorum gen. et sp. nov. revealed carotenoids and chlorophylls typical of green algae. Bioorganic analysis showed a complex lipidome based on phospho- (PC), galacto- (MGDG and DGDG), betaine- (DGTS), and sulfoquinovosyl- (SQDG) membrane lipids, besides significant amounts of storage neutral lipids such as diacyl- (DAG) and triacylglycerols (TAG). The presence of saturated alkyl chains within all the membrane lipid classes in P.desertorum and Asterarcys sp. appears to reflect the need to maintain membrane fluidity and viscosity. In summary, African deserts likely still harbor new taxa to be described, and lipidomic analyses of such taxa may provide clues about their ability to survive in the extremely harsh desert habitats.

No effect of prenatal vitamin D deficiency on autism-relevant behaviours in multiple inbred strains of mice

Autism Spectrum Disorders (ASD) is a group of neurodevelopmental disorders commonly characterised by verbal and non-verbal communication deficits, impaired social interaction and repetitive, stereotypic behaviours. The aetiology of ASD is most likely a combination of genetic and environmental factors. Epidemiological evidence suggests that prenatal vitamin D deficiency is associated with an increased incidence of ASD. The overall aim of this study was to investigate prenatal vitamin D deficiency on ASD-related behavioural phenotypes in multiple inbred strains of mice. We included two commonly used inbred mouse strains (C57BL/6J and BALB/c) as well as inbred BTBR mice, which show ASD-related behaviours, such as excessive self-grooming, hyperlocomotion, social interaction deficits and altered communication. We also studied the effect of prenatal vitamin D deficiency in a fourth strain; an F1 cross of C57BL/6J x BTBR mice, which have a partial BTBR phenotype. To implement prenatal vitamin D deficiency, female mice were placed on vitamin D deplete diets for ten weeks, including mating and gestation, until littering, when all dams were switched to the control diet. Behavioural symptoms related to ASD were measured, including isolation-induced ultrasonic vocalisations to measure communication, the three-chambered social interaction task to observe social interaction, the open field test to examine hyperlocomotion, assessment of grooming and rearing behaviour and finally the active place avoidance task to observe spatial learning and memory in response to a mild foot shock. Prenatal vitamin D deficiency had a negative impact on preference for social novelty in C57BL/6J mice, despite similar vocalisation phenotypes, and prenatal vitamin D-deficient F1 mice were found to be hypolocomotive in the open field test yet performed better on the active place avoidance task. Despite clear differences between strains, there were no other consistent significant main effects of maternal diet on the behaviour of the offspring. Vitamin D deficiency has been implicated as a risk factor for ASD and these data show that there is greater variation between different inbred strains in ASD-related behaviour, suggesting that prenatal vitamin D deficiency is not sufficient to recapitulate an ASD phenotype in multiple inbred strains of mice.

Multiresistant Acinetobacter baumannii ventriculitis

Among Gram-negative bacteria, Acinetobacter sp. has become an important nosocomial pathogen due to the increase in the number of multiresistant strains, and this species is responsible for a growing number of postoperative infections with a high mortality rate. The occurrence of multiresistant Gram-negative bacteria has led to an increase in the number of central nervous system infections and the occurrence of bacteria resistant to fourth-generation cephalosporins and carbapenems resulted in a significant reduction of therapeutic options for the treatment of these infections. Acinetobacter baumannii is an important nosocomial agent and its resistance to antibiotic has improved over the time and the occurrence of carbapenems and fourth generation cephalosporins resistant strains is a serious threaten to infected patients. We describe a case of a multi-resistant Acinetobacter baumannii resistant to fourth-generation cephalosporins and meropenem, after a neurosurgical procedure.

Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy adults ≥ 18 years of age: A randomized, multicenter, phase II / III clinical trial

ABSTRACTThis phase II / III clinical trial was conducted to evaluate the immunogenicity and safety of the Tetravalent Influenza vaccine (Split virion) I.P. (TetIV) developed indigenously in the country for the first time by M/s Cadila Healthcare Limited, India containing two influenza A and two influenza B strains, one of each, Yamagata (B/Phuket) and Victoria (B/Brisbane) lineage and also compare it to that of an licensed seasonal Trivalent Influenza vaccine (TriIV) of Sanofi Pasteur India Private Limited, containing the two influenza A and only the Yamagata lineage (B/Phuket) strain. Three hundred and fifty subjects of either sex, aged more than 18 years of age, were randomized in a 1:1 ratio to receive either the TetIV or TriIV. Immunogenicity assessments (antibody against A/H1N1, A/H3N2, B/Phuket and B/Brisbane) were done by Haemagglutination Inhibition assay at baseline and 21 d after vaccination. Solicited (local and systemic) and unsolicited adverse events were recorded for up to 42 d following vaccination. The TetIV was found to fulfill the criteria set by the European and the US regulatory authorities and WHO guidance on the requirements of clinical data for licensure of seasonal inactivated influenza vaccines. The seroconversion rates with TetIV were 93.5% for A/H1N1, 90.0% for A/H3N2, 70.0% for B/Phuket and 82.9% for B/Brisbane strain. There was no significant difference in the seroconversion and seroprotection rates at day 21 for A/H1N1, A/H3N2 and B/Phuket in the two groups while the TetIV was superior to the TrivIV for the seroconversion and the seroprotection rate for the B/Brisbane strain (Victoria lineage). Both the vaccines were well tolerated by all the study participants; addition of the fourth strain in the TetIV did not compromise the safety as compared to TriIV. The most common systemic adverse event reported in both the groups was headache followed by fever.

Virulence variation among strains of the emerging infectious fungus Batrachochytrium dendrobatidis (Bd) in multiple amphibian host species.

Emerging infectious diseases have been documented in numerous plant and animal populations. The infectious disease amphibian chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), is associated with global amphibian population declines. While much Bd-amphibian research has centered on response variation in hosts, a paucity of information exists on how variation in the pathogen, such as strain differences, affects infection dynamics. To examine how different Bd strains may differentially impact multiple hosts, we conducted laboratory experiments to measure 2 infection outcomes, viz. host survival and pathogen load, in 3 amphibian host species (Pacific treefrog, western toad, and Cascades frog) after exposure to 3 different Bd strains (an additional fourth Bd strain was tested in toads only). Our results confirm that the infection response differs among host species. Western toads experienced significant mortality, but Pacific treefrogs and Cascades frogs did not. Interestingly, our experiment also captured strain-dependent virulence variation but only in 1 host species, the western toad. Increased mortality was observed in 2 of the 4 Bd strains tested in this host species. Toads were also the only host species found to have variable pathogen load dependent on strain type; individuals exposed to the Panama strain harbored significantly higher loads compared to all other strains. These findings underscore the dynamic nature of Bd infection, showing that virulence can vary contingent on host and strain type. We highlight the importance of both host- and pathogen-dependent factors in determining overall infection virulence and show the need for in vivo testing to fully assess pathogenicity.