• Analysis of Bottlenecks in Experimental Models of Infection 

      Abel, Sören; Schulz Zur Wiesch, Pia; Davis, Brigid M.; Waldor, Matthew K. (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-06-11)
    • The bacterial magnesium transporter MgtA reveals highly selective interaction with specific cardiolipin species 

      Weikum, Julia; van Dyck, Jeroen F.; Subramani, Saranya; Klebl, David P.; Storflor, Merete; Muench, Stephen P.; Abel, Sören; Sobott, Frank; Morth, Jens Preben (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-10-23)
      The bacterial magnesium transporter A (MgtA) is a specialized P-type ATPase important for Mg<sup>2+</sup> import into the cytoplasm; disrupted magnesium homeostasis is linked to intrinsic ribosome instability and antibacterial resistance in Salmonella strains. Here, we show that MgtA has functional specificity for cardiolipin 18:1. Still, it reaches maximum activity only in combination with ...
    • Deciphering the landscape of host barriers to Listeria monocytogenes infection 

      Zhang, Ting; Abel, Sören; Abel zur Wiesch, Pia; Sasabe, Jumpei; Davis, Brigid M.; Higgins, Darren E. (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-30)
      <i>Listeria monocytogenes</i> is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate <i>L. monocytogenes</i> population dynamics during infection. We created a genetically barcoded library of murinized <i>L. monocytogenes</i> and then used deep sequencing to track ...
    • Drug-target binding quantitatively predicts optimal antibiotic dose levels in quinolones 

      Clarelli, Fabrizio; Palmer, Adam; Singh, Bhupender; Storflor, Merete; Lauksund, Silje; Cohen, Ted; Abel, Sören; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-08-14)
      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 of new antibiotics. Here, we describe a computational model (COMBAT-COmputational Model of Bacterial Antibiotic Target-binding) that can quantitatively predict antibiotic dose-response relationships. Our goal is dual: We address a ...
    • The Infectious Dose Shapes Vibrio Cholerae Within-Host Dynamics 

      Gillman, Aaron Nicholas; Mahmutovic, Anel; Abel zur Wiesch, Pia; Abel, Sören (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-07)
      During infection, the rates of pathogen replication, death, and migration affect disease progression, dissemination, transmission, and resistance evolution. Here, we follow the population dynamics of Vibrio cholerae in a mouse model by labeling individual bacteria with one of >500 unique, fitness-neutral genomic tags. Using the changes in tag frequencies and CFU numbers, we inform a mathematical ...
    • Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations 

      Hemez, Colin; Clarelli, Fabrizio; Palmer, Adam C.; Bleis, Christina; Abel, Sören; Chindelevitch, Leonid; Cohen, Theodore; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-08-24)
      Antibiotic-resistant pathogens are a major public health threat. A deeper understanding of how an antibiotic’s mechanism of action influences the emergence of resistance would aid in the design of new drugs and help to preserve the effectiveness of existing ones. To this end, we developed a model that links bacterial population dynamics with antibiotic-target binding kinetics. Our approach allows ...
    • Reaction Kinetic Models of Antibiotic Heteroresistance 

      Martinecz, Antal; Clarelli, Fabrizio; Abel, Sören; Abel zur Wiesch, Pia (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-15)
      Bacterial heteroresistance (i.e., the co-existence of several subpopulations with different antibiotic susceptibilities) can delay the clearance of bacteria even with long antibiotic exposure. Some proposed mechanisms have been successfully described with mathematical models of drug-target binding where the mechanism’s downstream of drug-target binding are not explicitly modeled and subsumed in ...
    • RESTAMP – Rate estimates by sequence-tag analysis of microbial populations 

      Mahmutovic, Anel; Gillman, Aaron Nicholas; Lauksund, Silje; Robson Moe, Natasha-Anne; Manzi, Aimé; Storflor, Merete; Abel-Zur Wiesch Genannt Hülsho, Pia Karoline; Abel, Sören (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-01-19)
      Microbial division rates determine the speed of mutation accumulation and thus the emergence of antimicrobial resistance. Microbial death rates are affected by antibiotic action and the immune system. Therefore, measuring these rates has advanced our understanding of host-pathogen interactions and antibiotic action. Several methods based on marker-loss or few inheritable neutral markers exist that ...
    • Selection or drift: The population biology underlying transposon insertion sequencing experiments 

      Mahmutovic, Anel; Abel zur Wiesch, Pia; Abel, Sören (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-03-25)
      <p>Transposon insertion sequencing methods such as Tn-seq revolutionized microbiology by allowing the identification of genomic loci that are critical for viability in a specific environment on a genome-wide scale. While powerful, transposon insertion sequencing suffers from limited reproducibility when different analysis methods are compared. From the perspective of population biology, this may be ...
    • Transposon-insertion sequencing screens unveil requirements for EHEC growth and intestinal colonization 

      Warr, Alyson R; Hubbard, Troy P; Munera, Diana; Blondel, Carlos J; Abel zur Wiesch, Pia; Abel, Sören; Wang, Xiaoxue; Davis, Brigid M.; Waldor, Matthew K. (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-08-12)
      Enterohemorrhagic <i>Escherichia coli</i> 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 <i>E. coli</i> K-12 growth <i>in vitro</i> and for EHEC growth <i>in vivo</i> in the infant rabbit colon. Surprisingly, many conserved loci contribute to EHEC’s but not to K-12’s growth <i>in ...