Secondary bacterial pneumonia due to Staphylococcus aureus complicating 2009 influenza A (H1N1) viral infection

ABSTRACTStaphylococcus aureusis a ubiquitous opportunistic human pathogen and a major health concern worldwide, causing a wide variety of diseases from mild skin infections to systemic disease.S. aureusis a major source of severe secondary bacterial pneumonia after influenza A virus infection, which causes widespread morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is well established, the mechanisms behind the transition from asymptomatic colonization to invasive staphylococcal disease following viral infection remains unknown. In this report, we have shown thatS. aureusbiofilms, grown on an upper respiratory epithelial substratum, disperse in response to host physiologic changes related to viral infection, such as febrile range temperatures, exogenous ATP, norepinephrine, and increased glucose. Mice that were colonized withS. aureusand subsequently exposed to these physiologic stimuli or influenza A virus coinfection developed pronounced pneumonia. This study provides novel insight into the transition from colonization to invasive disease, providing a better understanding of the events involved in the pathogenesis of secondary staphylococcal pneumonia.IMPORTANCEIn this study, we have determined that host physiologic changes related to influenza A virus infection causesS. aureusto disperse from a biofilm state. Additionally, we report that these same host physiologic changes promoteS. aureusdissemination from the nasal tissue to the lungs in an animal model. Furthermore, this study identifies important aspects involved in the transition ofS. aureusfrom asymptomatic colonization to pneumonia.

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Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia

Influenza and Other Respiratory Viruses ◽

10.1111/j.1750-2659.2011.00269.x ◽

2011 ◽

Vol 5 (6) ◽

pp. e535-e543 ◽

Cited By ~ 25

Author(s):

Joon Y. Song ◽

Hee J. Cheong ◽

Jung Y. Heo ◽

Ji Y. Noh ◽

Hwan S. Yong ◽

...

Keyword(s):

Pandemic Influenza ◽

Bacterial Pneumonia ◽

Influenza A ◽

Clinical Laboratory ◽

Influenza A H1n1 ◽

Influenza Pneumonia ◽

Secondary Bacterial Pneumonia ◽

H1n1 Pneumonia ◽

Radiologic Characteristics

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Streptococcus pneumoniae Modulates Staphylococcus aureus Biofilm Dispersion and the Transition from Colonization to Invasive Disease

mBio ◽

10.1128/mbio.02089-17 ◽

2018 ◽

Vol 9 (1) ◽

Cited By ~ 12

Author(s):

Ryan M. Reddinger ◽

Nicole R. Luke-Marshall ◽

Shauna L. Sauberan ◽

Anders P. Hakansson ◽

Anthony A. Campagnari

Keyword(s):

Staphylococcus Aureus ◽

Streptococcus Pneumoniae ◽

Influenza A Virus ◽

Bacterial Pneumonia ◽

Influenza A ◽

Bacterial Species ◽

Invasive Disease ◽

Secondary Bacterial Pneumonia

ABSTRACTStreptococcus pneumoniaeandStaphylococcus aureusare ubiquitous upper respiratory opportunistic pathogens. Individually, these Gram-positive microbes are two of the most common causative agents of secondary bacterial pneumonia following influenza A virus infection, and they constitute a significant source of morbidity and mortality. Since the introduction of the pneumococcal conjugate vaccine, rates of cocolonization with both of these bacterial species have increased, despite the traditional view that they are antagonistic and mutually exclusive. The interactions betweenS. pneumoniaeandS. aureusin the context of colonization and the transition to invasive disease have not been characterized. In this report, we show thatS. pneumoniaeandS. aureusform stable dual-species biofilms on epithelial cellsin vitro. When these biofilms are exposed to physiological changes associated with viral infection,S. pneumoniaedisperses from the biofilm, whereasS. aureusdispersal is inhibited. These findings were supported by results of anin vivostudy in which we used a novel mouse cocolonization model. In these experiments, mice cocolonized in the nares with both bacterial species were subsequently infected with influenza A virus. The coinfected mice almost exclusively developed pneumococcal pneumonia. These results indicate that despite our previous report thatS. aureusdisseminates into the lungs of mice stably colonized with these bacteria following influenza A virus infection, cocolonization withS. pneumoniae in vitroandin vivoinhibitsS. aureusdispersal and transition to disease. This study provides novel insight into both the interactions betweenS. pneumoniaeandS. aureusduring carriage and the transition from colonization to secondary bacterial pneumonia.IMPORTANCEIn this study, we demonstrate thatStreptococcus pneumoniaecan modulate the pathogenic potential ofStaphylococcus aureusin a model of secondary bacterial pneumonia. We report that host physiological signals related to viral infection cease to elicit a dispersal response fromS. aureuswhile in a dual-species setting withS. pneumoniae, in direct contrast to results of previous studies with each species individually. This study underscores the importance of studying polymicrobial communities and their implications in disease states.

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Faculty Opinions recommendation of Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1097147.553145 ◽

2007 ◽

Author(s):

Joseph Mizgerd

Keyword(s):

Influenza A Virus ◽

Bacterial Pneumonia ◽

Influenza A ◽

1918 Influenza ◽

Secondary Bacterial Pneumonia

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GP96 drives exacerbation of secondary bacterial pneumonia following influenza A virus infection

10.1101/2020.09.14.297192 ◽

2020 ◽

Author(s):

Tomoko Sumitomo ◽

Masanobu Nakata ◽

Satoshi Nagase ◽

Yuki Takahara ◽

Mariko Honda-Ogawa ◽

...

Keyword(s):

Epithelial Cells ◽

Influenza A Virus ◽

Transcriptional Repression ◽

Bacterial Pneumonia ◽

Influenza A ◽

Surface Expression ◽

Lung Pathology ◽

Direct Binding ◽

Novel Therapeutic Strategies ◽

Secondary Bacterial Pneumonia

AbstractInfluenza A virus (IAV) infection predisposes the host to secondary bacterial pneumonia, known as a major cause of morbidity and mortality during influenza epidemics. Analysis of interactions between IAV-infected human epithelial cells and Streptococcus pneumoniae revealed that infected cells ectopically exhibited the endoplasmic reticulum chaperon GP96 on the surface. Importantly, efficient pneumococcal adherence to epithelial cells was imparted by interactions with extracellular GP96 and integrin αV, with the surface expression mediated by GP96 chaperone activity. Furthermore, abrogation of adherence was gained by chemical inhibition or genetic knockout of GP96, as well as addition of RGD peptide. Direct binding of extracellular GP96 and pneumococci was shown to be mediated by pneumococcal oligopeptide permease components. Additionally, IAV infection induced activation of calpains and Snail1, which are responsible for degradation and transcriptional repression of junctional proteins in the host, respectively, indicating increased bacterial translocation across the epithelial barrier. Notably, treatment of IAV-infected mice with the GP96 inhibitor enhanced pneumococcal clearance from lung tissues and ameliorated lung pathology. Taken together, the present findings indicate a viral-bacterial synergy in relation to disease progression and suggest a paradigm for developing novel therapeutic strategies tailored to inhibit pneumococcal colonization in an IAV-infected respiratory tract.

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