Biology subjects

Falkowski, N. R.

Publications and source records attributed to Falkowski, N. R..

3 recordsLinked to original sources

bioRxiv2026

Novel Streptococcus mitis subsp. mitis Picklauza buccal isolate from individual with idiopathic pulmonary fibrosis containing functional mobile qacG Gene.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by immune dysregulation, fibrosis, and eventual respiratory failure. While the etiology of IPF remains unclear, accumulating evidence implicates the oral and airway microbiome in disease progression, with elevated Streptococcal burden linked to increased mortality. Whether specific taxa actively contribute to IPF pathophysiology or arise secondarily from the damaged lung environment remains unresolved. Here, we characterize "Picklauza," a streptococcal strain isolated from the buccal mucosa of an individual with IPF. Although its average nucleotide identity to a Streptococcus mitis reference genome was 93.855%, analysis with Streptoquod supported classification as Streptococcus mitis subsp. mitis. Genomic analysis identified a 109-amino-acid qacG homolog predicted to encode a small multidrug resistance (SMR)-family efflux transporter. The locus was located near genes associated with mobile genetic elements, raising the possibility of horizontal acquisition. The predicted QacG protein retained residues conserved in the extensively characterized SMR transporter EmrE, and RT-qPCR detected qacG transcripts under standard culture conditions. Nevertheless, Picklauza did not display increased tolerance to benzalkonium chloride, benzethonium chloride, or ethidium bromide compared with S. mitis NCTC 12261. Picklauza also differed from the reference strain in growth kinetics, carbon utilization, and antimicrobial susceptibility. PCR screening detected qacG homologs in three additional oral isolates from patients with IPF. Together, these findings identify a transcriptionally active, putatively mobile qacG homolog in oral streptococci while revealing a disconnect between gene carriage and QAC susceptibility under the conditions tested. This work highlights the need to validate predicted resistance determinants phenotypically and to investigate the mobility and conditional activity of SMR-family genes across genus boundaries in host-associated microbial communities.

microbiology↗

bioRxiv2025

Alveolar metabolite availability facilitates secondary infection by Pseudomonas aeruginosa in acutely injured lungs

Secondary bacterial pneumonia is a frequent complication of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Prior efforts to explain increased pneumonia risk in ALI/ARDS have focused on impaired immunity and bacterial virulence, but have overlooked the potential contribution of ecological factors within acutely injured lungs. Here, we show that lung injury profoundly alters the alveolar metabolic microenvironment, a change that can be exploited by a common pneumonia pathogen. In mice and humans, we found that growth of Pseudomonas aeruginosa (the most prominent respiratory pathogen in a retrospective cohort of patients with ARDS) is enhanced by increased alveolar concentrations of multiple ALI/ARDS-associated metabolites, which are derived from the blood and cross the compromised alveolar-capillary barrier during alveolar leak. Collectively, this work reveals an ecological mechanism by which pathogens may survive in the injured lung microenvironment and identifies new potential targets for secondary pneumonia prevention and treatment.

microbiology↗

bioRxiv2020

Application of an ecology-based analytic approach to discriminate signal and noise in low-biomass microbiome studies: whole lung tissue is the preferred sampling method for amplicon-based characterization of murine lung microbiota

BackgroundLow-biomass microbiome studies (such as those of the lungs, placenta, and skin) are vulnerable to contamination and sequencing stochasticity, which obscure legitimate microbial signal. Since low-biomass microbiome fields have had variable success in establishing the reality and clinical significance of identified microbiota, we sought to develop and apply an analytical approach to discriminate signal from noise in low-biomass microbiome studies. We used this approach to determine the optimal sampling strategy in murine lung microbiome studies, which will be essential for future mechanistic lung microbiome research. MethodsUsing a novel, ecology-based analytic approach, we compared bacterial DNA from the lungs of healthy adult mice collected via two common sampling approaches: homogenized whole lung tissue and bronchoalveolar lavage (BAL) fluid. We quantified bacterial DNA using droplet digital PCR, characterized bacterial communities using 16S rRNA gene sequencing, and systematically assessed the quantity and identity of bacterial DNA in both specimen types. We compared bacteria detected in lung specimens to each other and to potential source communities: negative (background) control specimens and paired oral samples. FindingsBy all measures, whole lung tissue in mice contained greater bacterial signal and less evidence of contamination than did BAL fluid. Relative to BAL fluid, whole lung tissue exhibited a greater quantity of bacterial DNA, distinct community composition, decreased sample-to-sample variation, and greater biological plausibility when compared to potential source communities. In contrast, bacteria detected in BAL fluid were minimally different from those of procedural, reagent, and sequencing controls. InterpretationAn ecology-based analytical approach discriminates signal from noise in low-biomass microbiome studies and identifies whole lung tissue as the preferred specimen type for murine lung microbiome studies. Sequencing, analysis, and reporting of potential source communities, including negative control specimens and contiguous biological sites, is crucial for biological interpretation of low-biomass microbiome studies, independent of specimen type. FundingNational Institutes of Health

microbiology↗