University of Louisville
Adaptations for an Obligate Intracellular Lifestyle: Molecular Evolution of Legionella pneumophila Ankyrin-Repeat Proteins
Institution
University of Louisville
Faculty Advisor/ Mentor
Awdhesh Kalia
Abstract
Legionella pneumophila serogroup 1 (Lpn sg1) isolates are responsible for most human Lpn infections. In silico analyses show that Lpn genomes harbour an expanded family of proteins containing a variable number of ankyrin-repeats, which themselves were acquired from eukaryotes. We showed that three of the Ank proteins, AnkB, AnkH, and AnkJ, contribute importantly to Lpn virulence. Here, we elucidated the molecular evolutionary dynamics of Ank proteins, in the context of Lpn’s population genetic structure in order to develop better insights into the emergence of Lpn sg1 isolates as the predominant cause of human infections. We implemented the Sequence-Based Typing (SBT) scheme established by the European Working Group on Legionella Infections, whereby nucleotide sequences of seven genes were determined from environmental (N=29) and clinical (N-20) origin. Three of these genes (asd, proA, and neuA) perform housekeeping functions, while (pilE, proA, mip, and mompS) are virulence associated. Analyses of mip and asd alleles revealed that environmental and clinical isolates are not phylogeneticaly distinct. In contrast, preliminary analyses of ankJ, ankH, and ankB revealed striking differences among environmental and clinical isolates. For example, we discovered an ankB variant, from mostly environmental Lpn isolates that contained a frameshift mutation causing deletion of the C-terminal signal sequence required for translocation via the Dot/Icm Type IV secretion system. Further population genetic and phylogenetic analyses of the completed allelic profiles is likely to provide greater insights in to the evolutionary origins of Lpn sg1 isolates and elucidate factors involved in adaptation to the human host.
Adaptations for an Obligate Intracellular Lifestyle: Molecular Evolution of Legionella pneumophila Ankyrin-Repeat Proteins
Legionella pneumophila serogroup 1 (Lpn sg1) isolates are responsible for most human Lpn infections. In silico analyses show that Lpn genomes harbour an expanded family of proteins containing a variable number of ankyrin-repeats, which themselves were acquired from eukaryotes. We showed that three of the Ank proteins, AnkB, AnkH, and AnkJ, contribute importantly to Lpn virulence. Here, we elucidated the molecular evolutionary dynamics of Ank proteins, in the context of Lpn’s population genetic structure in order to develop better insights into the emergence of Lpn sg1 isolates as the predominant cause of human infections. We implemented the Sequence-Based Typing (SBT) scheme established by the European Working Group on Legionella Infections, whereby nucleotide sequences of seven genes were determined from environmental (N=29) and clinical (N-20) origin. Three of these genes (asd, proA, and neuA) perform housekeeping functions, while (pilE, proA, mip, and mompS) are virulence associated. Analyses of mip and asd alleles revealed that environmental and clinical isolates are not phylogeneticaly distinct. In contrast, preliminary analyses of ankJ, ankH, and ankB revealed striking differences among environmental and clinical isolates. For example, we discovered an ankB variant, from mostly environmental Lpn isolates that contained a frameshift mutation causing deletion of the C-terminal signal sequence required for translocation via the Dot/Icm Type IV secretion system. Further population genetic and phylogenetic analyses of the completed allelic profiles is likely to provide greater insights in to the evolutionary origins of Lpn sg1 isolates and elucidate factors involved in adaptation to the human host.