Scott Chimileski, a postdoctoral Research Fellow in MSI co-director Roberto Kolter’s lab, accepted a 2016 Passion in Science Award in Arts and Creativity from New England Biolabs, Inc. Scott was chosen along with 14 other award winners from around the world for his microbe photography and his work to spearhead the Microbial Life exhibition at the Harvard Museum of Natural History, set to open in the fall of 2017. Scott also received a 2016 BioArt Award from the Federation of American Societies for Experimental Biology (FASEB) and was a winner of the 2016 Nikon Small World in Motion competition. Scott studies macroscopic patterns of microbial organizations, writes for the American Society of Microbiology's Microbial Science Blog and specializes in photography and microscopy.
See Scott’s microbe photography: http://www.scottchimileskiphotography.com/
Antibiotic resistance is a major threat to public health; specifically carbapenem-resistant enterobacteriaceae (CRE) are responsible for 11% of device-related noscomial infections. A recent prospective study by multiple institutes, with senior author MSI faculty member William Hanage, examined this phenomenon from coast to coast. Over the course of 16 months, the paper tracked CRE samples from patients in three Boston hospitals as well as from one California hospital. Among the samples, the most common resistant species were Klebisellia pneumoniae, Escherichia coli, and Enterobacter cloacae, with K. pneumoniae the most common species. About 65% of resistant bacteria had the blaKPC gene on transposable element Tn4401 encoding a ß-lactamase enzyme, which hydrolyzes carbapenems. However, many non-susceptible bacteria had unrecognized mechanisms of resistance. Researchers transformed a susceptible strain with the plasmids of resistant bacteria, and this transformation conferred meropenem resistant to the previously susceptible strains. By analyzing geographic data, researchers found that the different resistance mechanisms have degrees of relatedness based on geographic region. Using a pairwise SNP distance matrix, they found that sequence types from Boston were more closely related to each other than they were to sequence types from California. Overall, the study reveals the huge diversity of resistance mechanisms to carpapenems: current strategies of blaKPC gene detection to diagnose CRE may not detect all CREs.
Figure 1: Carbapenem-nonsusceptible Enterobacteriaceae from three Boston-area hospitals. Isolates are shown as squares (BIDMC), circles (BWH), and triangles (MGH). Isolates are stratified based on species and MLST (vertical axis) and with respect to time of collection (horizontal axis). Color indicates the predicted genetic determinant for meropenem nonsusceptibility. Isolates for which no genetic determinant was predicted are outline in red. Each rectangle on December 2012 represents two specimens collected from the same patient.
Prions, self-propagating aggregates of misfolded proteins, have previously been identified in fungus, yeast and other eukaryotes, but had not been found in bacteria. A recent paper by Andy Yuan in the MSI-affiliate Hochschild lab found a bacterial protein that can exist in prion form. Yuan used a hidden Markov model-based algorithm that had been trained by a set of prion forming proteins in yeast to search bacterial genomes for like genes. One of the hits was transcription termination factor Rho in Clostridium botulinum. Specifically, a candidate prion-forming domain (cPrD) was identified within this protein. Truncations of the protein lacking the cPrD were unable to form amyloid aggregates, while truncations with the cPrD showed amyloidogenicity, results that confirmed the 68 residue cPrD. Furthermore, the paper showed that this cPrD could replace that of yeast prion-forming protein Sup35. Cb-Rho-Sup35 chimeras were able to exist as folded proteins or as prions, depending on the presence of chaperone protein. Cb-Rho was also cloned into E. coli and through a reporter gene assay was shown to exist in the soluble and aggregated form. Bacteria with the aggregated prion form showed genome-wide changes in the transcriptome. This study is notable not only in showing that prions likely predated the divergence of bacteria and eukaryotes but also in identifying prions as possible epigenetic effectors that contribute to genetic diversity.
Figure 2: (A) Cartoon of a Rho hexamer engaging RNA polymerase (RNAP) (top) and domain organization of Cb-Rho highlighting its cPrD and NID (bottom), where numbered dots indicate specific residues. (B) E. coli cells exporting the indicated protein domain were spotted on solid medium containing the amyloid-binding dye Congo Red (CR). The PrD of yeast Sup35 (Sup35NM) and its derivative (Sup35M) serve as positive and negative controls, respectively. Plate-derived material visualized by bright-field microscopy and between crossed polarizers reveals “apple-green” birefringence characteristically exhibited by CR-bound amyloid aggregates.