<i>Pseudomonas aeruginosa</i> promotes persistence of <i>Stenotrophomonas maltophilia</i> via increased adherence to depolarized respiratory epithelium

McDaniel, Melissa S.; Lindgren, Natalie; Billiot, Caitlin E; Valladeres, Kristina N.; Sumpter, Nicholas A; Swords, W. Edward

doi:10.1101/2022.06.29.498203

Cited by 2 publications

(2 citation statements)

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“…CFBE cells were grown at ALI and infected with an MOI of 10 of each bacterial strain for 6 hours, after which the cells were fixed in ice cold methanol-acetone (1:1) and immunofluorescently stained using a previously published protocol (42,43). Cryosectioned lung tissue sections (5 μm/section) from infected mice were stained using polyclonal anti-Ax rabbit sera and .…”

Section: Immunofluorescent Stainingmentioning

confidence: 99%

Pathogenesis ofAchromobacter xylosoxidansrespiratory infections: colonization and persistence of airway epithelia and differential gene expression in synthetic cystic fibrosis sputum medium

Billiot

McDaniel

Lindgren

et al. 2023

Preprint

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Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long respiratory mucosal infections caused by a diverse array of opportunists, and these infections are a leading cause of morbidity and mortality for pwCF. In recent years, there has been increased appreciation for the range and diversity of microbes in CF-related respiratory infections. Introduction of new therapeutics and improved detection methodology has revealed CF related opportunists such as Achromobacter xylosoxidans (Ax). Ax is a Gram-negative bacterial species that is widely distributed in the environment and has been increasingly observed in sputa and other samples from pwCF; typically Ax infections occur in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of Ax and tested colonization and persistence of Ax in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical Ax isolates showed homologs for factors involved in flagellar synthesis, antibiotic resistance, and toxin secretion systems. Ax isolates adhered to polarized CFBE14o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization. Ax colonized and persisted in mouse lung for up to 72 hours post infection, with inflammatory consequences that include increased neutrophilia, lung damage, cytokine production, and mortality. Transcript profiling reveled differential expression of Ax genes during growth in SCFM2 synthetic CF sputum media. Based on these results, we conclude that Ax is an opportunistic pathogen of significance in CF.

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Section: Immunofluorescent Stainingmentioning

confidence: 99%

Pathogenesis ofAchromobacter xylosoxidansrespiratory infections: colonization and persistence of airway epithelia and differential gene expression in synthetic cystic fibrosis sputum medium

Billiot

McDaniel

Lindgren

et al. 2023

Preprint

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“…aeruginosa contributed to the increased persistence of S. maltophilia [22–24]. These studies were, however, restricted to only a few strains, and given the amount of genetic diversity present in S.…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals genetic diversity which correlates with colonization and persistence in vivo

McDaniel,

Sumpter,

Lindgren

et al. 2023

Microbiology

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Stenotrophomonas maltophilia is a Gram-negative emerging opportunistic pathogen often present in people with respiratory diseases such as cystic fibrosis (CF). People with CF (pwCF) experience lifelong polymicrobial infections of the respiratory mucosa. Our prior work showed that Pseudomonas aeruginosa promotes persistence of S. maltophilia in mouse respiratory infections. As is typical for environmental opportunistic pathogens, S. maltophilia has a large genome and a high degree of genetic diversity. In this study, we evaluated the genomic content of S. maltophilia, combining short and long read sequencing to construct nearly complete genomes of 10 clinical isolates. The genomes of these isolates were then compared with all publicly available S. maltophilia genome assemblies, and each isolate was then evaluated for colonization/persistence in vivo, both alone and in coinfection with P. aeruginosa . We found that while the overall genome size and GC content were fairly consistent between strains, there was considerable variability in both genome structure and gene content. Similarly, there was significant variability in S. maltophilia colonization and persistence in experimental mouse respiratory infections in the presence or absence of P. aeruginosa . Ultimately, this study gives us a greater understanding of the genomic diversity of clinical S. maltophilia isolates, and how this genomic diversity relates to both interactions with other pulmonary pathogens and to host disease progression. Identifying the molecular determinants of infection with S. maltophilia can facilitate development of novel antimicrobial strategies for a highly drug-resistant pathogen.

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Pseudomonas aeruginosa promotes persistence of Stenotrophomonas maltophilia via increased adherence to depolarized respiratory epithelium

Cited by 2 publications

References 50 publications

Pathogenesis ofAchromobacter xylosoxidansrespiratory infections: colonization and persistence of airway epithelia and differential gene expression in synthetic cystic fibrosis sputum medium

Pathogenesis ofAchromobacter xylosoxidansrespiratory infections: colonization and persistence of airway epithelia and differential gene expression in synthetic cystic fibrosis sputum medium

Comparative genomics of clinical Stenotrophomonas maltophilia isolates reveals genetic diversity which correlates with colonization and persistence in vivo

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