scholarly journals Staphylococcus aureusBiofilm Growth on Cystic Fibrosis Airway Epithelial Cells Is Enhanced during Respiratory Syncytial Virus Coinfection

mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Megan R. Kiedrowski ◽  
Jordan R. Gaston ◽  
Brian R. Kocak ◽  
Stefanie L. Coburn ◽  
Stella Lee ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Respiratory Syncytial Virus ◽  
Biofilm Formation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Biofilm Growth ◽  
Content Type ◽  
Syncytial Virus ◽  
Polymicrobial Infections

ABSTRACTStaphylococcus aureusis a major cause of chronic respiratory infection in patients with cystic fibrosis (CF). We recently showed thatPseudomonas aeruginosaexhibits enhanced biofilm formation during respiratory syncytial virus (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of respiratory viruses on other bacterial pathogens during polymicrobial infections in CF remains largely unknown. To investigate ifS. aureusbiofilm growth in the CF airways is impacted by virus coinfection, we evaluatedS. aureusgrowth on CF AECs. Initial studies showed an increase inS. aureusgrowth over 24 h, and microscopy revealed biofilm-like clusters of bacteria on CF AECs. Biofilm growth was enhanced when CF AECs were coinfected with RSV, and this observation was confirmed withS. aureusCF clinical isolates. Apical conditioned medium from RSV-infected cells promotedS. aureusbiofilms in the absence of the host epithelium, suggesting that a secreted factor produced during virus infection benefitsS. aureusbiofilms. Exogenous iron addition did not significantly alter biofilm formation, suggesting that it is not likely the secreted factor. We further characterizedS. aureus-RSV coinfection in our model using dual host-pathogen RNA sequencing, allowing us to observe specific contributions ofS. aureusand RSV to the host response during coinfection. Using the dual host-pathogen RNA sequencing approach, we observed increased availability of nutrients from the host and upregulation ofS. aureusgenes involved in growth, protein translation and export, and amino acid metabolism during RSV coinfection.IMPORTANCEThe airways of individuals with cystic fibrosis (CF) are commonly chronically infected, andStaphylococcus aureusis the dominant bacterial respiratory pathogen in CF children. CF patients also experience frequent respiratory virus infections, and it has been hypothesized that virus coinfection increases the severity ofS. aureuslung infections in CF. We investigated the relationship betweenS. aureusand the CF airway epithelium and observed that coinfection with respiratory syncytial virus (RSV) enhancesS. aureusbiofilm growth. However, iron, which was previously found to be a significant factor influencingPseudomonas aeruginosabiofilms during virus coinfection, plays a minor role inS. aureuscoinfections. Transcriptomic analyses provided new insight into how bacterial and viral pathogens alter host defense and suggest potential pathways by which dampening of host responses to one pathogen may favor persistence of another in the CF airways, highlighting complex interactions occurring between bacteria, viruses, and the host during polymicrobial infections.

scholarly journals Tomatidine Inhibits Replication of Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Airway Epithelial Cells

2011 ◽  
Vol 55 (5) ◽  
pp. 1937-1945 ◽  
Author(s):  
Gabriel Mitchell ◽  
Mariza Gattuso ◽  
Gilles Grondin ◽  
Éric Marsault ◽  
Kamal Bouarab ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Electron Transport ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Plant Secondary Metabolite ◽  
Airway Epithelial ◽  
Small Colony Variants ◽  
Content Type ◽  
Small Colony

ABSTRACTSmall-colony variants (SCVs) often are associated with chronicStaphylococcus aureusinfections, such as those encountered by cystic fibrosis (CF) patients. We report here that tomatidine, the aglycon form of the plant secondary metabolite tomatine, has a potent growth inhibitory activity against SCVs (MIC of 0.12 μg/ml), whereas the growth of normalS. aureusstrains was not significantly altered by tomatidine (MIC, >16 μg/ml). The specific action of tomatidine was bacteriostatic for SCVs and was clearly associated with their dysfunctional electron transport system, as the presence of the electron transport inhibitor 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) caused normalS. aureusstrains to become susceptible to tomatidine. Inversely, the complementation of SCVs' respiratory deficiency conferred resistance to tomatidine. Tomatidine provoked a general reduction of macromolecular biosynthesis but more specifically affected the incorporation of radiolabeled leucine in proteins of HQNO-treatedS. aureusat a concentration corresponding to the MIC against SCVs. Furthermore, tomatidine inhibited the intracellular replication of a clinical SCV in polarized CF-like epithelial cells. Our results suggest that tomatidine eventually will find some use in combination therapy with other traditional antibiotics to eliminate persistent forms ofS. aureus.

scholarly journals Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2055
Author(s):  
Andrew R. Connelly ◽  
Brian M. Jeong ◽  
Mackenzie E. Coden ◽  
Jacob Y. Cao ◽  
Tatiana Chirkova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Early Life ◽  
Airway Epithelial Cells ◽  
Metabolic Reprogramming ◽  
Flux Analysis ◽  
Nasal Airway ◽  
Airway Epithelial ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

scholarly journals The Virulence Potential of Livestock-Associated Methicillin-Resistant Staphylococcus aureus Cultured from the Airways of Cystic Fibrosis Patients

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 360
Author(s):  
Janina Treffon ◽  
Sarah Ann Fotiadis ◽  
Sarah van Alen ◽  
Karsten Becker ◽  
Barbara C. Kahl
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Airway Epithelial Cells ◽  
Farm Animals ◽  
Airway Epithelial ◽  
Methicillin Resistant ◽  
Virulence Potential ◽  
Airway Infections ◽  
Severe Infections

Staphylococcus aureus is one of the most common pathogens that infects the airways of patients with cystic fibrosis (CF) and contributes to respiratory failure. Recently, livestock-associated methicillin-resistant S. aureus (LA-MRSA), usually cultured in farm animals, were detected in CF airways. Although some of these strains are able to establish severe infections in humans, there is limited knowledge about the role of LA-MRSA virulence in CF lung disease. To address this issue, we analyzed LA-MRSA, hospital-associated (HA-) MRSA and methicillin-susceptible S. aureus (MSSA) clinical isolates recovered early in the course of airway infection and several years after persistence in this hostile environment from pulmonary specimens of nine CF patients regarding important virulence traits such as their hemolytic activity, biofilm formation, invasion in airway epithelial cells, cytotoxicity, and antibiotic susceptibility. We detected that CF LA-MRSA isolates were resistant to tetracycline, more hemolytic and cytotoxic than HA-MRSA, and more invasive than MSSA. Despite the residence in the animal host, LA-MRSA still represent a serious threat to humans, as such clones possess a virulence potential similar or even higher than that of HA-MRSA. Furthermore, we confirmed that S. aureus individually adapts to the airways of CF patients, which eventually impedes the success of antistaphylococcal therapy of airway infections in CF.

scholarly journals Respiratory Syncytial Virus Up-regulates TLR4 and Sensitizes Airway Epithelial Cells to Endotoxin

2003 ◽  
Vol 278 (52) ◽  
pp. 53035-53044 ◽  
Author(s):  
Martha M. Monick ◽  
Timur O. Yarovinsky ◽  
Linda S. Powers ◽  
Noah S. Butler ◽  
A. Brent Carter ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Syncytial Virus

scholarly journals Protective role of Indoleamine 2,3 dioxygenase in Respiratory Syncytial Virus associated immune response in airway epithelial cells

Virology ◽  
2017 ◽  
Vol 512 ◽  
pp. 144-150 ◽  
Author(s):  
Devi Rajan ◽  
Raghavan Chinnadurai ◽  
Evan L. O'Keefe ◽  
Seyhan Boyoglu-Barnum ◽  
Sean O. Todd ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Protective Role ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Indoleamine 2,3 Dioxygenase ◽  
Syncytial Virus
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