Dr. Patrick Curtis

Patrick_Curtis

Associate Professor
Department of Biology
The University of Mississippi

Contact:

Office: 402 Shoemaker Hall
Email: pdcurtis@olemiss.edu
Telephone: 662-915-1911

Research

index_clip_image002_0000My lab is interested in how bacteria adapt, repurpose and integrate signaling pathways to create complex cellular systems, particularly those of prokaryotic development. The model developmental bacterium Caulobacter crescentus has a dimorphic life cycle where after division the two resulting daughter cells have differing life styles. One cell has a thin cellular extension called the stalk; this cell can immediately re-enter the replication cycle. The other cell has a flagellum and is motile (swarmer cell), but cannot replicate. The swarmer cell must differentiate into a stalked cell before it can initiate replication. C. crescentus utilizes multiple regulatory systems (including global, temporally-controlled, and spatially-regulated systems) to create morphological and intracellular signaling asymmetry during cell division, but the extent and function of these systems are not well understood. My lab aims to understand the mechanisms by which these systems function.

Projects

Brevundimonas subvibrioides as a model organism
A close relative of C. crescentus, Brevundimonas subvibrioides, has the same developmental life cycle and the same developmental signaling system components. However, our research has shown that even if the signaling components are conserved between the organisms, their operation can show dramatic differences. The protein GcrA functions with a DNA methyltransferase CcrM to epigenetically regulate dozens of genes during the C. crescentus life cycle. We have found that GcrA/CcrM regulon in B. subvibrioides has remarkably little overlap with the C. crescentus regulon, with only a handful of common regulatory targets. In another example, disruption of the essential developmental signaling gene divK in C. crescentus leads to pleiotropic defects in polar development, including motility, adhesion and pilus formation. The B. subvibrioides divK gene encodes a protein 80% identical to the C. crescentus counterpart, but the B. subvibrioides gene is non-essential, and disruption leads to opposite phenotypes in nearly all processes. We are exploring these systems to find how and why systems that are so similar in composition diverge so greatly in consequence.

Caulobacter crescentus pilus biogenesis
C. crescentus produces several polar pili during the swarmer cell which are important for surface colonization. These pili are from the specific flp family of Type IV pili; the function, composition, and synthesis of this family is comparatively less well-known than other Type IV pili. We are using C. crescentus as a model to study this pilus system. The pilA gene, which encodes for the pilin monomer, is a regulatory target of the C. crescentus master regulator CtrA, a global regulator that influences the expression of over 100 genes. Interestingly, the pilA gene is expressed later in the cell cycle than other CtrA-dependent genes, which likely is important for specific timing of pilus biogenesis during the cell cycle. We are currently exploring the mechanism of pilA expression to determine just how differential timing of expression is achieved, and why that might be important for the organism. Additionally, the pili are localized the same pole as the flagellum, but the mechanism of polar localization is not understood even though it appears to be a common feature of flp pili. We are researching potential polar localization mechanisms for the pilus structure.

Genome-level analysis of essential genes
Bacterial genomes typically contain thousands of genes, but only a fraction of those genes have any predicted function. Finding functions for unknown genes is difficult as mutagenesis and physiological characterization of individual genes is a time- and effort-intensive process. We were among the pioneers of the TnSeq method, where a target organism is extensively mutagenized with a transposon, and then insertion sites are mapped by high-throughput sequencing. By identifying which genes can tolerate transposon insertions and which genes cannot, we can identify which genes are essential under a given condition. Performing this analysis under multiple conditions can reveal which genes are always essential, and which are important for survival under a more specific condition. This method provides a high-throughput, systems-level physiological characterization of the entire genome, and can provide novel insight into gene function. We have published the essential genomes of B. subvibrioides, Agrobacterium tumefaciens, and Rubrivivax gelatinosus. We have also collaborated on a project which performed TnSeq in C. crescentus grown in natural lakewater, and are pursuing other TnSeq projects as well.

Teaching

BISC 333 – General Microbiology
BISC 438 – Bacterial Physiology
BISC 637 – Prokaryotic Development

Education

1997-2001 B.Sc., Purdue University – Microbiology, Genetics
2001-2007 Ph.D., University of Georgia – Microbiology
2007-2012 Postdoc, Indiana University – Dr. Yves V. Brun

Publications

Curtis, PD. Bacterial Development. In Encyclopedia of Microbiology (4e). Elsevier. In press.

Hentchel, KL, LM Reyes Ruiz, PD Curtis, A Fiebig, ML Coleman, Crosson S. 2019. Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater.  ISME J.  2019 Feb;13(2):523-536.

Curtis, PD. 2017. Stalk formation of Brevundimonas and how it compares to Caulobacter crescentus. PLoS One. 12(9):e0184063.

Adhikari, S and PD Curtis. 2016. DNA methyltransferases and epigenetic regulation in bacteria. FEMS Microbiol Rev. 40(5):575-91.

Curtis, PD. 2016. Essential Genes Predicted in the Genome of Rubrivivax gelatinosus. J Bacteriol. 198(16):2244-50.

Curtis, PD and YV Brun. 2014. Identification of essential Alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems. Mol Microbiol. 93(4):713-35.

Curtis, PD, D Klein and YV Brun. 2013. Effect of a ctrA promoter mutation causing a reduction in CtrA abundance on the cell cycle and development of Caulobacter crescentus. BMC Microbiol. 13:166:1-12.

Curtis PD, Quardokus EM, Lawler ML, Guo X, Klein D, Chen JC, Arnold RJ, Brun YV. 2012. The scaffolding and signaling functions of a localization factor impact polar development. Mol Microbiol. 84:712-35.

Curtis, PD and YV Brun. 2010. Getting in the loop: regulation of development in Caulobacter crescentus. Microbiol Mol Biol Rev. 74:13-41.

Curtis, PD and YV Brun. 2010. A novel effector protein modulates response regulator activity without altering phosphorylation. Mol Cell. 39:319-20. [Preview article]

Curtis, PD and LJ Shimkets. 2008. Metabolic pathways relevant to predation, signaling, and development. p. 241-258. In DE Whitworth (ed), Myxobacteria III. ASM Press, Washington D.C.

Curtis, PD, RG Taylor, RE Welch and LJ Shimkets. 2007. Spatial organization of Myxococcus xanthus during fruiting body formation. J Bacteriol. 189:9126-30.

Curtis, PD, J Atwood 3rd, R Orlando and LJ Shimkets. 2007. Proteins associated with the Myxococcus xanthus extracellular matrix. J Bacteriol. 189:7634-42.

Curtis, PD, R Geyer, DC White and LJ Shimkets. 2006. Novel lipids in Myxococcus xanthus and their role in chemotaxis. Environ Microbiol. 8:1935-49.

Curtis, P, CH Nakatsu and A Konopka. 2002. Aciduric Proteobacteria isolated from pH 2.9 soil. Arch Microbiol. 178:65-70.