A Commensal Streptococcus Dysregulates the Pseudomonas aeruginosa Nitrosative Stress Response

Baty, Joshua J.; Huffines, Joshua T.; Stoner, Sara N.; Scoffield, Jessica

doi:10.3389/fcimb.2022.817336

Cited by 5 publications

(4 citation statements)

References 76 publications

(108 reference statements)

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“…Prevotella is consistently the core bacteria of the respiratory tract [ 25 , 26 ]. Previous studies have demonstrated that commensal bacteria can interact with airway pathogens, such as Pseudomonas aeruginosa , to improve lung function and clinical stability [ 27 , 28 ]. As a result, we assumed that the specific airway microbiome composed of these commensal bacteria could inhibit MP and maintain lung environmental homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia

Huang,

Luo,

Wang

et al. 2024

Respir Res

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Background This study aimed to investigate the interactions among three core elements of respiratory infection—pathogen, lung microbiome, and host response—and their avocation with the severity and outcomes of Mycoplasma pneumoniae pneumonia (MPP) in children. Methods We prospectively collected bronchoalveolar lavage fluid from a cohort of 41 children with MPP, including general MPP (GMPP) and complicated MPP (CMPP), followed by microbiome and transcriptomic analyses to characterize the association among pathogen, lung microbiome, and host response and correlate it with the clinical features and outcomes. Results The lung microbiome of patients with CMPP had an increased relative abundance of Mycoplasma pneumoniae (MP) and reduced alpha diversity, with 76 differentially expressed species. Host gene analysis revealed a key module associated with neutrophil function and several inflammatory response pathways. Patients with a high relative abundance of MP, manifested by a specific lung microbiome and host response type, were more prone to CMPP and had a long imaging recovery time. Conclusion Patients with CMPP have a more disrupted lung microbiome than those with GMPP. MP, lung microbiome, and host response interacts with each other and are closely related to disease severity and outcomes in children with MPP. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia

Huang,

Luo,

Wang

et al. 2024

Respir Res

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“…One possibility is the antagonism of CF pathogens by streptococci. Our laboratory has previously demonstrated that H 2 O 2 -producing streptococci, such as S. parasanguinis , can inhibit P. aeruginosa through the generation of RNI ( 18 , 20 ). Another possible mechanism is that these streptococci can modulate the host immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Nitrite can also react with H 2 O 2 to form reactive nitrogen intermediates (RNIs) that are antimicrobial. This commensal-generated RNI antagonism has been documented to inhibit oral pathogens as well as the CF pathogen Pseudomonas aeruginosa ( 18 , 35 , 36 ).…”

Section: Introductionmentioning

confidence: 99%

“…Previously, our laboratory has shown that Streptococcus parasanguinis, an oral commensal that is prevalent in clinically stable pwCF, can inhibit P. aeruginosa in a nitrite-dependent manner. This work indicated that P. aeruginosa is sensitive to RNIs in vitro and in a Drosophila melanogaster infection model ( 20 ), that the presence of S. parasanguinis alters the P. aeruginosa denitrification response ( 18 , 45 ), and that CF isolates of P. aeruginosa are particularly sensitive to these RNIs ( 18 ). Thus, antagonism of P. aeruginosa through RNI may be a mechanism that explains why oral commensal streptococci are correlated with improved outcomes in pwCF.…”

Section: Introductionmentioning

confidence: 99%

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An oral commensal attenuates Pseudomonas aeruginosa -induced airway inflammation and modulates nitrite flux in respiratory epithelium

Baty,

Stoner,

McDaniel

et al. 2023

Microbiol Spectr

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Polymicrobial airway infections in persons with cystic fibrosis (pwCF) can positively or negatively impact the course of disease. A major CF pathogen, Pseudomonas aeruginosa, often establishes a chronic infection leading to lung deterioration. Interestingly, the presence of certain oral commensal streptococci is correlated with improved outcomes for pwCF. We previously reported that hydrogen peroxide production by these commensals combined with nitrite generates reactive nitrogen intermediates (RNI), which inhibit P. aeruginosa in vitro . In this study, we utilized a rat co-infection lung model to assess whether oral commensal-generated RNI can restrict the pathogenesis of a CF isolate of P. aeruginosa . We report that the oral commensal Streptococcus parasanguinis and nitrite reduce P. aeruginosa -induced host inflammation in wild-type rats. To better recapitulate CF-specific airway conditions, we used a bronchial epithelial cell culture model to gain a better understanding of how S. parasanguinis and nitrite may influence P. aeruginosa burden during a CF infection. Hence, we co-infected wild-type and cystic fibrosis transconductance regulator (CFTR) channel-deficient bronchial epithelial cells with P. aeruginosa and S. parasanguinis with or without nitrite. Strikingly, S. parasanguinis reduced the bacterial burden of P. aeruginosa without nitrite, promoted epithelial cell viability, and stimulated nitrite production in the wild-type and CFTR-deficient epithelial cells, where nitrite induction was more apparent in the CFTR mutant cells. Taken together, our study demonstrates that the commensal S. parasanguinis may provide protection against P. aeruginosa -induced inflammation and cell death, as well as modulate nitrite flux in airway epithelial cells. IMPORTANCE Respiratory infections are a leading cause of morbidity and mortality in people with cystic fibrosis (CF). These infections are polymicrobial in nature with overt pathogens and other colonizing microbes present. Microbiome data have indicated that the presence of oral commensal bacteria in the lungs is correlated with improved outcomes. We hypothesize that one oral commensal, Streptococcus parasanguinis, inhibits CF pathogens and modulates the host immune response. One major CF pathogen is Pseudomonas aeruginosa , a Gram-negative, opportunistic bacterium with intrinsic drug resistance and an arsenal of virulence factors. We have previously shown that S. parasanguinis inhibits P. aeruginosa in vitro in a nitrite-dependent manner through the production of reactive nitrogen intermediates. In this study, we demonstrate that while this mechanism is evident in a cell culture model of the CF airway, an alternative mechanism by which S. parasanguinis may improve outcomes for people with CF is through immunomodulation.

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Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat

Bollar,

Keith,

Stanford

et al. 2024

The American Journal of Pathology

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A Commensal Streptococcus Dysregulates the Pseudomonas aeruginosa Nitrosative Stress Response

Cited by 5 publications

References 76 publications

Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia

Integrative study of pulmonary microbiome, transcriptome and clinical outcomes in Mycoplasma pneumoniae pneumonia

An oral commensal attenuates Pseudomonas aeruginosa -induced airway inflammation and modulates nitrite flux in respiratory epithelium

Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat

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