Secondary streptococcal infection following influenza

Okahashi, Nobuo; Sumitomo, Tomoko; Nakata, Masao; Kawabata, Shigetada

doi:10.1111/1348-0421.12965

Cited by 16 publications

(14 citation statements)

References 122 publications

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“…IAV infects the upper respiratory tract and oral mitis group streptococci are inhabitants of the oral cavity [2,6,[33][34][35]. The interaction between IAV and S. pneumoniae, a pathogenic member of the mitis group, have been intensively investigated [2,20,21,[36][37][38][39]; however, the interaction between IAV and oral streptococci has not been well studied.…”

Section: Discussionmentioning

confidence: 99%

“…Poor oral hygiene is reported to be correlated with occurrence of respiratory diseases such as bacterial pneumonia [16], and professional oral healthcare has been shown to reduce the risk of IAV infection [17]. The interaction between IAV and S. pneumoniae has been intensively investigated [15,[18][19][20][21], however, interaction between IAV and oral streptococci is not well understood. Several studies have shown that neuraminidase (NA)-producing streptococci such as S. pneumoniae and oral mitis group streptococci potentially elevate the risk of influenza because NA plays an essential role in IAV infection [13,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Oral mitis group streptococci reduce infectivity of influenza A virus via acidification and H2O2 production

Okahashi

Sumitomo²,

Nakata³

et al. 2022

PLoS ONE

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Members of the mitis group streptococci are the most abundant inhabitants of the oral cavity and dental plaque. Influenza A virus (IAV), the causative agent of influenza, infects the upper respiratory tract, and co-infection with Streptococcus pneumoniae is a major cause of morbidity during influenza epidemics. S. pneumoniae is a member of mitis group streptococci and shares many features with oral mitis group streptococci. In this study, we investigated the effect of viable Streptococcus oralis, a representative member of oral mitis group, on the infectivity of H1N1 IAV. The infectivity of IAV was measured by a plaque assay using Madin-Darby canine kidney cells. When IAV was incubated in growing culture of S. oralis, the IAV titer decreased in a time- and dose-dependent manner and became less than 100-fold, whereas heat-inactivated S. oralis had no effect. Other oral streptococci such as Streptococcus mutans and Streptococcus salivarius also reduced the viral infectivity to a lesser extent compared to S. oralis and Streptococcus gordonii, another member of the oral mitis group. S. oralis produces hydrogen peroxide (H2O2) at a concentration of 1–2 mM, and its mutant deficient in H2O2 production showed a weaker effect on the inactivation of IAV, suggesting that H2O2 contributes to viral inactivation. The contribution of H2O2 was confirmed by an inhibition assay using catalase, an H2O2-decomposing enzyme. These oral streptococci produce short chain fatty acids (SCFA) such as acetic acid as a by-product of sugar metabolism, and we also found that the inactivation of IAV was dependent on the mildly acidic pH (around pH 5.0) of these streptococcal cultures. Although inactivation of IAV in buffers of pH 5.0 was limited, incubation in the same buffer containing 2 mM H2O2 resulted in marked inactivation of IAV, which was similar to the effect of growing S. oralis culture. Taken together, these results reveal that viable S. oralis can inactivate IAV via the production of SCFAs and H2O2. This finding also suggests that the combination of mildly acidic pH and H2O2 at low concentrations could be an effective method to inactivate IAV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oral mitis group streptococci reduce infectivity of influenza A virus via acidification and H2O2 production

Okahashi

Sumitomo²,

Nakata³

et al. 2022

PLoS ONE

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“…Bacterial co-infections with viruses represent a considerable challenge to public health, and for S. pneumoniae, influenza virus is the major pathogen leading to secondary pneumococcal infections (13). Antibiotic-resistance further compounds the difficulty of treating co-infected patients (41), so the search for alternative therapies is of significant importance. Influenza virus is able to suppress alveolar macrophage cell function within 7 days of infection (22,42).…”

Section: Discussionmentioning

confidence: 99%

Synergistic protection against secondary pneumococcal infection by human monoclonal antibodies targeting distinct epitopes

Gingerich

Royer

McCormick

et al. 2022

Preprint

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Streptococcus pneumoniae persists as a leading cause of bacterial pneumonia despite the widespread use of polysaccharide-based vaccines. The limited serotype coverage of current vaccines has led to increased incidence of non-vaccine serotypes, as well as an increase in antibiotic resistance among these serotypes. Pneumococcal infection often follows a primary viral infection such as influenza virus, which hinders host defense and results in bacterial spread to the lungs. We previously isolated human monoclonal antibodies (mAbs) against the conserved surface antigen pneumococcal histidine triad protein D (PhtD), and we demonstrated that mAbs to this antigen are protective against lethal pneumococcal challenge prophylactically and therapeutically. In this study, we elucidated the mechanism of protection of a protective anti- pneumococcal human mAb, PhtD3, which is mediated by the presence of complement and macrophages in a mouse model of pneumococcal infection. Treatment with mAb PhtD3 reduced blood and lung bacterial burden in mice, and mAb PhtD3 is able to bind to bacteria in the presence of the capsular polysaccharide, indicating exposure of surface PhtD on encapsulated bacteria. In a mouse model of secondary pneumococcal infection, protection mediated by mAb PhtD3 and another mAb targeting a different epitope, PhtD7, was reduced, however, robust protection was restored by combining mAb PhtD3 with mAb PhtD7, indicating a synergistic effect. Overall, these studies provide new insights into anti-pneumococcal mAb protection and demonstrate for the first time that mAbs to pneumococcal surface proteins can protect against secondary pneumococcal infection in the mouse model.Author SummaryThe persistence of Streptococcus pneumoniae as a leading cause of bacterial pneumonia despite numerous approved pneumococcal vaccines is a serious threat to public health globally. Currently, prophylactic and therapeutic options for Streptococcus pneumoniae are constrained by the limited serotype coverage of vaccines and the emergence of antibiotic resistant strains. An additional hurdle to overcome is the incidence of secondary pneumococcal infection following a viral infection, which leads to increased mortality. Here, we determined the mechanism of action of a monoclonal antibody (mAb) that targets Streptococcus pneumoniae. We found that mAb PhtD3 operates through macrophage and complement mediated functions. mAb PhtD3 was also discovered to reduce bacterial titers in the lungs and blood and bind to a related antigen PhtE. We also tested additional mAbs and discovered that two unique mAbs to the antigen PhtD conferred protection in a pneumococcal-influenza virus co-infection model. Our study provides new insights into the mechanisms and therapeutic potential of mAbs targeting conserved proteins of Streptococcus pneumoniae.

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“…We speculate that acidification of the airway fluids during infection mitigates the effectiveness of the AMPs, facilitating common co- or secondary-infection with Streptococcus pneumoniae in the respiratory epithelium caused by influenza [ 137 ]. Proximal IAV infection would appear to be stimulated by the neuraminidase-expressing streptococci, which include certain oral mitis group streptococci.…”

Section: Spectrum Of Amp Activity Across Microbial Kingdomsmentioning

confidence: 99%

Antimicrobial peptides: Defending the mucosal epithelial barrier

Johnstone

Herzberg

2022

Front. Oral. Health

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The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of commensals over pathogenic microbes. The canonical AMPs are helictical peptides that form lethal pores in microbial membranes. In higher life forms, this type of AMP is exemplified by the defensin family of AMPs. In epithelial tissues, defensins, and calprotectin (complex of S100A8 and S100A9) have evolved to work cooperatively. The mechanisms of action differ. Unlike defensins, calprotectin sequesters essential trace metals from microbes, which inhibits growth. This review focuses on defensins and calprotectin as AMPs that appear to work cooperatively to fortify the epithelial barrier against infection. The antimicrobial spectrum is broad with overlap between the two AMPs. In mice, experimental models highlight the contribution of both AMPs to candidiasis as a fungal infection and periodontitis resulting from bacterial dysbiosis. These AMPs appear to contribute to innate immunity in humans, protecting the commensal microflora and restricting the emergence of pathobionts and pathogens. A striking example in human innate immunity is that elevated serum calprotectin protects against neonatal sepsis. Calprotectin is also remarkable because of functional differences when localized in epithelial and neutrophil cytoplasm or released into the extracellular environment. In the cytoplasm, calprotectin appears to protect against invasive pathogens. Extracellularly, calprotectin can engage pathogen-recognition receptors to activate innate immune and proinflammatory mechanisms. In inflamed epithelial and other tissue spaces, calprotectin, DNA, and histones are released from degranulated neutrophils to form insoluble antimicrobial barriers termed neutrophil extracellular traps. Hence, calprotectin and other AMPs use several strategies to provide microbial control and stimulate innate immunity.

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Secondary streptococcal infection following influenza

Cited by 16 publications

References 122 publications

Oral mitis group streptococci reduce infectivity of influenza A virus via acidification and H2O2 production

Oral mitis group streptococci reduce infectivity of influenza A virus via acidification and H2O2 production

Synergistic protection against secondary pneumococcal infection by human monoclonal antibodies targeting distinct epitopes

Antimicrobial peptides: Defending the mucosal epithelial barrier

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