Haley Echlin
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Resistance, heteroresistance, and fitness costs drive colistin treatment failure during <i>Acinetobacter baumannii</i> pneumonia Open
Acinetobacter baumannii is an Enterococcus , Staphylococcus , Klebsiella , Acinetobacter , Pseudomonas , and Enterobacter species (ESKAPE) pathogen linked to healthcare-associated diseases. Due to evolved resistance, last-resort antibiotic…
Resistance, heteroresistance and fitness costs drive colistin treatment failure during <i>Acinetobacter baumannii</i> pneumonia Open
Acinetobacter baumannii is an ESKAPE pathogen linked to healthcare-associated diseases. Due to evolved resistance, last-resort antibiotics such as the lipooligosaccharide (LOS)-targeting colistin are increasingly used to treat multidrug-re…
A Trivalent Live Vaccine Elicits Cross-Species Protection Against Acute Otitis Media in a Murine Model Open
Background: Acute otitis media (AOM) is a common pediatric infection worldwide and is the primary basis for pediatric primary care visits and antibiotic prescriptions in children. Current licensed vaccines have been incompletely ineffectiv…
<i>Streptococcus pneumoniae</i> favors tolerance via metabolic adaptation over resistance to circumvent fluoroquinolones Open
The increasing prevalence of antibiotic resistant bacteria is a major global health concern. While many species have the potential to develop antibiotic resistance, understanding the barriers to resistance emergence in the clinic remains p…
Airway proteolytic control of pneumococcal competence Open
Streptococcus pneumoniae is an opportunistic pathogen that colonizes the upper respiratory tract asymptomatically and, upon invasion, can lead to severe diseases including otitis media, sinusitis, meningitis, bacteremia, and pneumonia. One…
Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae Open
As opposed to de novo mutation, β-lactam resistance in S. pneumoniae is often conferred via homologous recombination during horizontal gene transfer. We hypothesize that β-lactam resistance in pathogenic streptococci is restricted to natur…
Pneumococcal Evasion of Antibiotics via Metabolic Adaptation During Infection Open
Streptococcus pneumoniae is a major human pathogen of global health concern, causing a range of mild to severe infections, including acute otitis media, pneumonia, sepsis, and meningitis. The rapid emergence of antibiotic resistance among …
View article: Magnetic Bead-Based Separation (MBS) of Pneumococcal Serotypes
Magnetic Bead-Based Separation (MBS) of Pneumococcal Serotypes Open
SUMMARY The separation of pneumococcal serotypes from a complex polymicrobial mixture may be required for different applications. For instance, a minority strain could be present at a low frequency in a clinical sample, making it difficult…
Pneumococcal Colonization and Virulence Factors Identified Via Experimental Evolution in Infection Models Open
Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. We examined adaptation and evolution of pneumococcus, within nasopharynx and lungs, in an experimental system where the…
Identification of colonisation and virulence determinants of <i>Streptococcus pneumoniae</i> via experimental evolution in mouse infection models Open
Streptococcus pneumoniae is a commensal of the human nasopharynx and a major cause of respiratory and invasive disease. Pneumococcus stimulates upper respiratory tract inflammation that promotes shedding from mucosal surfaces and transmiss…
Respiratory Bacteria Stabilize and Promote Airborne Transmission of Influenza A Virus Open
Infection with influenza A virus (IAV), especially when complicated with a secondary bacterial infection, is a leading cause of global mortality and morbidity. Gaining a greater understanding of the transmission dynamics of IAV is importan…
Advancing Genetic Tools in Streptococcus pneumoniae Open
Streptococcus pneumoniae is the causative agent of a multitude of diseases, and further study into its pathogenies is vital. The pneumococcus is genetically malleable, and several tools are available to manipulate this pathogen. In this st…
Respiratory bacteria stabilize and promote airborne transmission of influenza A virus Open
Influenza A virus (IAV) is a major pathogen of the human respiratory tract where the virus co-exists and interacts with bacterial populations comprising the respiratory microbiome. Synergies between IAV and respiratory bacterial pathogens …
Advancing Genetic Tools in <em>Streptococcus Pneumoniae</em> Open
Streptococcus pneumoniae is the causative agent of a multitude of diseases and further study into its pathogenies is vital. The pneumococcus is genetically malleable and several tools are available to manipulate this pathogen. In this stud…
Role of the pyruvate metabolic network on carbohydrate metabolism and virulence in <i>Streptococcus pneumoniae</i> Open
Streptococcus pneumoniae is a major human pathogen that must adapt to unique nutritional environments in several host niches. The pneumococcus can metabolize a range of carbohydrates that feed into glycolysis ending in pyruvate, which is c…
The Transcriptional landscape of Streptococcus pneumoniae TIGR4 reveals a complex operon architecture and abundant riboregulation critical for growth and virulence Open
Efficient and highly organized regulation of transcription is fundamental to an organism's ability to survive, proliferate, and quickly respond to its environment. Therefore, precise mapping of transcriptional units and understanding their…
Model of glucose metabolism in <i>S</i>. <i>pneumoniae</i>. Open
Model of glucose metabolism in S. pneumoniae.
Capsule production is reduced in the TIGR4 <i>spxB</i> mutant. Open
Capsule production was measured in two methods. In the first, cell lysates from wild type and the spxB, lctO, and double spxB/lctO mutants in either TIGR4 (A) or D39 (B) backgrounds and the wild type and spxB mutant of the capsule swapped …
TIGR4 <i>spxB</i> mutant has reduced virulence in an IN mouse model. Open
BALB/c mice were infected IN with 1 x 107 cells. Bacterial presence in the blood in mice infected with TIGR4 strains was determined by detection of colony forming units (CFU/mL) at 24 hours (A) and 48 hours (B) post infection. In the same …
Deletion of <i>spxB</i> in TIGR4, but not in D39, demonstrates resistance to LL-37 killing. Open
The growth of cells in increasing concentration of LL-37 (0, 10, 21, and 42 μg/ mL) was measured. Strains include those in type 4 background—TIGR4 (A) and the spxB (B), lctO (C), and double spxB-lctO (D) mutants—and those in type 2 backgro…
TIGR4 <i>spxB</i> mutant is not lethal in an IP mouse model. Open
BALB/c mice were infected IP with 1 x 103 cells and monitored for disease progression. Mice were infected with TIGR4 and the spxB, lctO, and double spxB-lctO mutants. Bacterial presence in the blood was determined at 24 hours (A) post infe…
Fluorescence against surface capsule is greatly diminished in the TIGR4 <i>spxB</i> mutant. Open
Capsule production was detected using fluorescence microscopy using primary antibodies against type 2 or 4 capsules with a fluorescent secondary (green) and DAPI stain to detect DNA (blue). Three representative images of TIGR4 (A) and the …
Acetyl-CoA steady-state levels were reduced in the TIGR4 <i>spxB</i> mutant. Open
TIGR4 capsule consists of several sugars that are acetylated, unlike the capsule of D39. Capsule units are abbreviated: Pyr (pyruvate); Gal (galactose); ManNAc (N-acetyl-mannosamine); FucNAc (N-acetyl-fucosamine); GalNAc (N-acetyl-galactos…
Capsule on the cell surface is undetectable in the TIGR4 <i>spxB</i> mutant. Open
Cell surface structures of TIGR4 (A) and the spxB (B), lctO (C), and double spxB lctO (D) mutants were imaged using transmission electron microscopy. Scale bars are 600 nm in the image and 200 nm in the inset.
Loss of capsule in <i>spxB</i> mutant is conserved and secondary mutations can reverse this phenotype. Open
Capsule production was measured using capsule blotting method. Strains used include wild type, spxB mutant, and spxB mutant revertant (rev) from four strains with serotype four capsule, including TIGR4, ABCA69, ABCB20, and ABCB54 (A). Caps…
D39 <i>spxB</i> mutant maintains virulence in an IN mouse model. Open
BALB/c mice were infected IN with 1 x 107 cells. Bacterial presence in the blood in mice infected with D39 strains was determined at 24 hours (A) and 48 hours (B) post infection. In the same mice, bacterial carriage in the nasopharynx was …
Pyruvate Oxidase as a Critical Link between Metabolism and Capsule Biosynthesis in Streptococcus pneumoniae Open
The pneumococcus is one of the most prodigious producers of hydrogen peroxide amongst bacterial pathogens. Hydrogen peroxide production by the pneumococcus has been implicated in antibiotic synergism, competition between other bacterial co…