Neuraminidase-producing oral mitis group streptococci potentially contribute to influenza viral infection and reduction in antiviral efficacy of zanamivir

Kamio, Noriaki; Imai, Kenichi; Shimizu, Kazufumi; Cueno, Marni E.; Tamura, Muneaki; Saito, Yuko; Ochiai, Kuniyasu

doi:10.1007/s00018-014-1669-1

Cited by 30 publications

(39 citation statements)

References 44 publications

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“…mitis group species are important colonizers of the oral cavity, and are occasionally associated with serious infections [ 15 ]. In addition, these organisms have recently been suggested to play important roles in the pathogenesis of influenza [ 8 ]. Therefore, the genomic study of diverse S .…”

Section: Resultsmentioning

confidence: 99%

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StreptoBase: An Oral Streptococcus mitis Group Genomic Resource and Analysis Platform

et al. 2016

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The oral streptococci are spherical Gram-positive bacteria categorized under the phylum Firmicutes which are among the most common causative agents of bacterial infective endocarditis (IE) and are also important agents in septicaemia in neutropenic patients. The Streptococcus mitis group is comprised of 13 species including some of the most common human oral colonizers such as S. mitis, S. oralis, S. sanguinis and S. gordonii as well as species such as S. tigurinus, S. oligofermentans and S. australis that have only recently been classified and are poorly understood at present. We present StreptoBase, which provides a specialized free resource focusing on the genomic analyses of oral species from the mitis group. It currently hosts 104 S. mitis group genomes including 27 novel mitis group strains that we sequenced using the high throughput Illumina HiSeq technology platform, and provides a comprehensive set of genome sequences for analyses, particularly comparative analyses and visualization of both cross-species and cross-strain characteristics of S. mitis group bacteria. StreptoBase incorporates sophisticated in-house designed bioinformatics web tools such as Pairwise Genome Comparison (PGC) tool and Pathogenomic Profiling Tool (PathoProT), which facilitate comparative pathogenomics analysis of Streptococcus strains. Examples are provided to demonstrate how StreptoBase can be employed to compare genome structure of different S. mitis group bacteria and putative virulence genes profile across multiple streptococcal strains. In conclusion, StreptoBase offers access to a range of streptococci genomic resources as well as analysis tools and will be an invaluable platform to accelerate research in streptococci. Database URL: http://streptococcus.um.edu.my.

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Section: Resultsmentioning

confidence: 99%

“…mitis were found to produce neuraminidase (NA), a vital target of anti-influenza drugs. The NA activity exhibited by these oral bacteria stimulates the release of influenza virus, boosts viral M1 protein expression levels and activates the cell signaling ERK pathway, potentially enhancing viral infections [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

StreptoBase: An Oral Streptococcus mitis Group Genomic Resource and Analysis Platform

et al. 2016

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“…An increase in the number of S. mitis cases could also have hampered the efficacy of the viral neuraminidase inhibitor drug. 21 Of the four H1N1 patients who died, S. mitis was present in three.…”

Section: Discussionmentioning

confidence: 97%

“…The 8-month-old male had eight symptoms and harbored S. mitis , which could have elevated the risk of and exacerbated the influenza infection. 21 …”

Section: Discussionmentioning

confidence: 99%

Molecular diagnosis of microbial copathogens with influenza A(H1N1)pdm09 in Oaxaca, Mexico

Ramírez-Palacios

Reséndez‐Pérez

Rodríguez-Padilla

et al. 2018

RRTM

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BackgroundMultiple factors have been associated with the severity of infection by influenza A(H1N1)pdm09. These include H1N1 cases with proven coinfections showing clinical association with bacterial contagions.PurposeThe objective was to identify H1N1 and copathogens in the Oaxaca (Mexico) population. A cross-sectional survey was conducted from 2009 to 2012. A total of 88 study patients with confirmed H1N1 by quantitative RT-PCR were recruited.MethodsTotal nucleic acid from clinical samples of study patients was analyzed using a TessArray RPM-Flu microarray assay to identify other respiratory pathogens.ResultsHigh prevalence of copathogens (77.3%; 68 patients harbored one to three pathogens), predominantly from Streptococcus, Haemophilus, Neisseria, and Pseudomonas, were detected. Three patients (3.4%) had four or five respiratory copathogens, whereas others (19.3%) had no copathogens. Copathogenic occurrence with Staphylococcus aureus was 5.7%, Coxsackie virus 2.3%, Moraxella catarrhalis 1.1%, Klebsiella pneumoniae 1.1%, and parainfluenza virus 3 1.1%. The number of patients with copathogens was four times higher to those with H1N1 alone (80.68% and 19.32%, respectively). Four individuals (4.5%; two males, one female, and one infant) who died due to H1N1 were observed to have harbored such copathogens as Streptococcus, Staphylococcus, Haemophilus, and Neisseria.ConclusionIn summary, copathogens were found in a significant number (>50%) of cases of influenza in Oaxaca. Timely detection of coinfections producing increased acuity or severity of disease and treatment of affected patients is urgently needed.

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“…NA, an envelope glycoprotein on the surface of the influenza virus, catalyses the cleavage of sialic acids on glycoproteins from virus-infected cells and enables virus release [18, 19]. Studies have demonstrated that low NA enzyme activity renders virus release from infected cells inefficient and leaves progeny viruses gathered on the cell surface [19, 20]. DCs represent a central element in the generation and maintenance of immune responses [21].…”

Section: Discussionmentioning

confidence: 99%

MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3

et al. 2016

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Neuraminidase (NA), a structural protein of the H9N2 avian influenza virus (H9N2 AIV), can facilitate viral invasion of the upper airway by cleaving the sialic acid moieties on mucin. Dendritic cells (DCs) are major antigen-presenting cells whose immune functions, such as presenting antigens and activating lymphocytes, can be regulated by microRNAs. Here, we studied the molecular mechanism of miRNA-induced repression of immune responses in mouse DCs. First, we screened for and verified the miRNAs induced by NA. Then, we showed that, consistent with the H9N2 virus treatment, the viral NA up-regulated the expression of miR-155, miR-674, and miR-499 in DCs; however, unlike H9N2 virus treatment, the presence of NA was associated with reduced expression of miR-181b1. Our results suggest that NA significantly increased DC surface markers CD80 and MHCII and enhanced the ability of activating lymphocytes and secreting cytokines compared with HA, NP and M2. Meanwhile, we found that miR-674 and miR-155 over-expression increased all surface markers of DC. Nevertheless, by inhibiting the expression of miR-674 and miR-155, NA lost the ability to promote DC maturation. Furthermore, we predicted and demonstrated that Pgm2l1, Aldh18a1, Camk1d, and Mbnl3 were the target genes of miR-674. Among them, Mbnl3 interference strongly blocked the mature DCs. Collectively, our data shed new light on the roles of and mechanisms involved in the repression of DCs by miRNAs, which may contribute to efforts to develop a prophylaxis for the influenza virus.

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Neuraminidase-producing oral mitis group streptococci potentially contribute to influenza viral infection and reduction in antiviral efficacy of zanamivir

Cited by 30 publications

References 44 publications

StreptoBase: An Oral Streptococcus mitis Group Genomic Resource and Analysis Platform

StreptoBase: An Oral Streptococcus mitis Group Genomic Resource and Analysis Platform

Molecular diagnosis of microbial copathogens with influenza A(H1N1)pdm09 in Oaxaca, Mexico

MiR674 inhibits the neuraminidase-stimulated immune response on dendritic cells via down-regulated Mbnl3

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