A5091699409- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Evolution and Genetic Dynamics
- Tuberculosis Research and Epidemiology
- Vibrio bacteria research studies
- Antibiotic Use and Resistance
- Pneumocystis jirovecii pneumonia detection and treatment
- Escherichia coli research studies
- Cancer therapeutics and mechanisms
- Bacterial Genetics and Biotechnology
- Bacterial Identification and Susceptibility Testing
- Diagnosis and treatment of tuberculosis
- Urinary Tract Infections Management
- Salmonella and Campylobacter epidemiology
- Drug Transport and Resistance Mechanisms
- Bacteriophages and microbial interactions
- Clostridium difficile and Clostridium perfringens research
- Infectious Diseases and Tuberculosis
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Aquaculture disease management and microbiota
- Protein purification and stability
- SARS-CoV-2 and COVID-19 Research
- Bacterial biofilms and quorum sensing
- Plant Virus Research Studies
UiT The Arctic University of Norway
2015-2024
Pennsylvania State University
2020-2024
Norwegian Institute of Public Health
2020-2024
University of Siegen
2024
Center for Disease Dynamics, Economics & Policy
2020-2022
Brigham and Women's Hospital
2013-2019
Harvard University
2013-2019
Yale University
2015-2019
Harvard Global Health Institute
2015
ETH Zurich
2011-2014
Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion use combination requires knowledge how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal are most potent with actively dividing cells, then inhibition growth induced by a bacteriostatic drug should result an overall reduction efficacy when drug. Our goal here investigate this hypothesis systematically. We first constructed...
Many bacteria mediate important life-style decisions by varying levels of the second messenger c-di-GMP. Behavioral transitions result from coordination complex cellular processes such as motility, surface adherence or production virulence factors and toxins. While regulatory mechanisms responsible for these have been elucidated in some cases, global pleiotropic effects c-di-GMP are poorly understood, primarily because networks inherently most bacteria. Moreover, quantitative relationships...
Significance We conducted a genome-wide screen to identify bacterial factors required for Vibrio parahaemolyticus , an important cause of seafood-borne gastroenteritis, survive in vitro and colonize the mammalian intestine. Our analysis revealed uncharacterized components horizontally acquired type III secretion system linked virulence (T3SS2) hundreds genes that likely contribute colonization independent T3SS2. work toxR conserved gene vibrios governs expression cholerae was critical Thus,...
The evolution of resistance to antimicrobial chemotherapy is a major and growing cause human mortality morbidity. Comparatively little attention has been paid how different patient treatment strategies shape the resistance. In particular, it not clear whether treating individual patients aggressively with high drug dosages long durations, or moderately low short durations can better prevent spread Here, we summarize very limited available empirical evidence across pathogens provide...
Chemical reaction kinetics explain three different effects of drug-mediated bacterial killing.
Significance Deep sequencing of bar-coded Listeria monocytogenes enabled determination the pathogen’s dissemination routes and founding population sizes. The gallbladder, which is seeded by very few L. cells, becomes source for pathogen shedding in feces. low complexity shed populations suggests that genetic drift may be a powerful force evolution. Innate immune factors microbiota differentially regulate establishment proliferation at distal sites. Sequence tag-based analysis microbial...
Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an important food-borne pathogen that colonizes the colon. Transposon-insertion sequencing (TIS) was used to identify genes required for EHEC and E. K-12 growth in vitro vivo infant rabbit Surprisingly, many conserved loci contribute EHEC’s but not K-12’s vitro. There a restrictive bottleneck colonization of colon, which complicated identification facilitating vivo. Both refined version existing analytic framework as well PCA-based...
Antibiotic resistant nosocomial infections are an important cause of mortality and morbidity in hospitals. cycling has been proposed to contain this spread by a coordinated use different antibiotics. Theoretical work, however, suggests that often the random deployment drugs ("mixing") might be better strategy. We epidemiological model for single hospital ward order assess performance strategies which take into account frequency antibiotic resistance ward. assume information on frequencies...
The evolution of drug resistant bacteria is a severe public health problem, both in hospitals and the community. Currently, some countries aim at concentrating highly specialized services large order to improve patient outcomes. Emergent strains often originate care facilities, but it unknown what extent hospital size affects resistance resulting spillover hospital-associated pathogens We used two published datasets from US Ireland investigate effects controlled for several confounders such...
BackgroundThe projected long-term prevalence of multidrug-resistant (MDR) tuberculosis depends upon the relative fitness MDR Mycobacterium strains, compared with non-MDR strains. While many experimental models have tested in vitro or vivo costs various drug resistance mutations, fewer epidemiologic studies attempted to validate these findings.
Treatment failure after therapy of pulmonary tuberculosis (TB) infections is an important challenge, especially when it coincides with de novo emergence multi-drug-resistant TB (MDR-TB). We seek to explore possible causes why MDR-TB has been found occur much more often in patients a history previous treatment. develop mathematical model the replication Mycobacterium within patient reflecting compartments macrophages, granulomas, and open cavities as well parameterizing effects drugs on...
Identifying optimal dosing of antibiotics has proven challenging—some are most effective when they administered periodically at high doses, while others work best minimizing concentration fluctuations. Mechanistic explanations for why differ in their lacking, limiting our ability to predict therapy and leading long costly experiments. We use mathematical models that describe both bacterial growth intracellular antibiotic-target binding investigate the effects fluctuating antibiotic...
Antibiotic resistance is rising and we urgently need to gain a better quantitative understanding of how antibiotics act, which in turn would also speed up the development new antibiotics. Here, describe computational model (COMBAT-COmputational Model Bacterial Target-binding) that can quantitatively predict antibiotic dose-response relationships. Our goal dual: We address fundamental biological question investigate drug-target binding shapes action. create tool efficacy priori. COMBAT...
During infection, the rates of pathogen replication, death, and migration affect disease progression, dissemination, transmission, resistance evolution. Here, we follow population dynamics Vibrio cholerae in a mouse model by labeling individual bacteria with one >500 unique, fitness-neutral genomic tags. Using changes tag frequencies CFU numbers, inform mathematical that describes within-host spatiotemporal bacterial dynamics. This allows us to disentangle growth, forward, retrograde...
To understand how antibiotic use affects the risk of a resistant infection, we present computational model population dynamics gut microbiota including resistance-conferring plasmids. We then describe this is parameterized based on published data. Finally, investigate treatment history prevalence resistance among opportunistic enterobacterial pathogens. simulate histories and identify which properties prior exposure are most influential in determining resistance. find that can be predicted...
Treatment of infectious diseases is often long and requires patients to take drugs even after they have seemingly recovered. This because a phenomenon called persistence, which allows small fractions the bacterial population survive treatment despite being genetically susceptible. The surviving subpopulation below detection limit therefore empirically inaccessible but can cause failure when terminated prematurely. Mathematical models could aid in predicting survival thereby determine...