ArticlePLoS pathogens2018
Microevolution in response to transient heme-iron restriction enhances intracellular bacterial community development and persistence.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- A 5'-UTR cis-acting RNA element targeted by RNase III is essential for DNA simple sequence repeat-dependent phase variation in Haemophilus influenzae.Nucleic acids research · 2025Article
- Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025Review
- Heme sequestration by hemophilin frommSphere · 2024Article
- Modeling airway persistent infection ofFrontiers in cellular and infection microbiology · 2024Article
- Adaptive immune protection of the middle ears differs from that of the respiratory tract.Frontiers in cellular and infection microbiology · 2023Article
- Commensal Bacteria in the Cystic Fibrosis Airway Microbiome ReduceFrontiers in cellular and infection microbiology · 2022Article
- Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients.Frontiers in cardiovascular medicine · 2021Article
- Learning from -omics strategies applied to uncoverComputational and structural biotechnology journal · 2021Review
- Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection.Cell reports · 2020Article
- Panel 7 - Pathogenesis of otitis media - a review of the literature between 2015 and 2019.International journal of pediatric otorhinolaryngology · 2020Review
- COPD-Related Modification to the Airway Epithelium Permits Intracellular Residence of NontypeableInternational journal of chronic obstructive pulmonary disease · 2020Article
- NOD1/NOD2-mediated recognition of non-typeableInnate immunity · 2019Article
- Heme Uptake and Utilization by Gram-Negative Bacterial Pathogens.Frontiers in cellular and infection microbiology · 2019Review
- Archaea Symbiont ofFrontiers in cellular and infection microbiology · 2018Article
- Reprioritization of biofilm metabolism is associated with nutrient adaptation and long-term survival ofNPJ biofilms and microbiomesArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Bacterial pathogens must sense, respond and adapt to a myriad of dynamic microenvironmental stressors to survive. Adaptation is key for colonization and long-term ability to endure fluctuations in nutrient availability and inflammatory processes. We hypothesize that strains adapted to survive nutrient deprivation are more adept for colonization and establishment of chronic infection. In this study, we detected microevolution in response to transient nutrient limitation through mutation of icc. The mutation results in decreased 3',5'-cyclic adenosine monophosphate phosphodiesterase activity in nontypeable Haemophilus influenzae (NTHI). In a preclinical model of NTHI-induced otitis media (OM), we observed a significant decrease in the recovery of effusion from ears infected with the icc mutant strain. Clinically, resolution of OM coincides with the clearance of middle ear fluid. In contrast to this clinical paradigm, we observed that the icc mutant strain formed significantly more intracellular bacterial communities (IBCs) than the parental strain early during experimental OM. Although the number of IBCs formed by the parental strain was low at early stages of OM, we observed a significant increase at later stages that coincided with absence of recoverable effusion, suggesting the presence of a mucosal reservoir following resolution of clinical disease. These data provide the first insight into NTHI microevolution during nutritional limitation and provide the first demonstration of IBCs in a preclinical model of chronic OM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.