Dr. 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

My 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.

Bacterial responses to microgravity
Physiological changes during spaceflight are well documented for animals and plants, but many people assume bacteria, with their incredibly small size, do not respond to microgravity.  In fact, many bacteria have been shown to have altered characteristics when cultured under microgravity conditions.  Unfortunately, many bacterial microgravity studies are limited in scope.  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.  This method provides a high-throughput, systems-level physiological characterization of the entire genome, and can provide novel insight into gene function.  We have applied this methodology to studies of microgravity by culturing TnSeq libraries of a few organisms aboard the International Space Station.  We hope our work will provide broader, systems-level insight into bacterial responses to microgravity.  We are also working on microgravity responses in plant-friendly bacteria in the hopes of improving plant health when grown aboard spacecraft.”

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

Mascolo, E, S Adhikari, SM Caruso, T deCarvalho, AF Salvador, J Serra-Sagristà, RF Young, I Erill, PD Curtis. 2022.  The transcriptional regulator CtrA controls gene expression in Alphaproteobacteria phages: evidence for a lytic deferment pathway.  Front. Microbiol. 13:918015. DOI: 10.3389/fmicb.2022.918015

Sharma, G and PD Curtis.  2022.  The Impacts of Microgravity on Bacterial Metabolism.  Life 12(6), 774.      PMID: 35743807 PMCID: PMC9225508 DOI: 10.3390/life12060774

Sharma, G and PD Curtis. 2022.  The use of TnSeq to identify essential alphaproteobacterial genes reveals operational variability in conserved developmental and cell cycle systems. Methods Mol Bio. 2377:259-271.  PMID: 34709621 DOI: 10.1007/978-1-0716-1720-5_14

Adhikari, S, I Erill and PD Curtis. 2021.  Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria.  PLoS Genet.  Mar 11;17(3):e1009433.  PMID: 33705385 PMCID: PMC7987155 DOI: 10.1371/journal.pgen.1009433

Sperling, L, MD Mulero Alegria, V Kaever, and PD Curtis. 2019.  Analysis of Brevundimonas subvibrioides developmental signaling systems reveals inconsistencies between phenotypes and c-di-GMP levels.  J Bacteriol. Sep 20;201(20):e00447-19.  PMID: 31383736 PMCID: PMC6755725 DOI: 10.1128/JB.00447-19

Curtis PD. 2019.  Bacterial Development. In: Schmidt, Thomas M. (ed.) Encyclopedia of Microbiology, 4th Edition. vol. 1, pp. 388-397. UK: Elsevier.  DOI: 10.1016/B978-0-12-809633-8.20669-9

Hentchel, KL, LM Reyes Ruiz, PD Curtis, A Fiebig, ML Coleman, and S Crosson. 2019. Genome-scale fitness profile of Caulobacter crescentus grown in natural freshwater.  ISME J. 13(2):523-536.  PMID: 30297849 PMCID: PMC6331620 DOI: 10.1038/s41396-018-0295-6 

Curtis, PD. 2017. Stalk formation of Brevundimonas and how it compares to Caulobacter crescentus.  PLoS One. 12(9):e0184063.  PMID: 28886080 PMCID: PMC5590869 DOI: 10.1371/journal.pone.0184063

Adhikari, S and PD Curtis.  2016.  DNA methyltransferases and epigenetic regulation in bacteria.  FEMS Microbiol Rev.  40(5):575-91.  PMID: 27476077 DOI: 10.1093/femsre/fuw023

Curtis, PD.  2016.  Essential Genes Predicted in the Genome of Rubrivivax gelatinosus.  J Bacteriol.  198(16):2244-50.  PMID: 27274029 PMCID: PMC4966436 DOI: 10.1128/JB.00344-16

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.  PMID: 24975755 PMCID: PMC4132054 DOI: 10.1111/mmi.12686

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.       PMID: 23865946 PMCID: PMC3751295 DOI: 10.1186/1471-2180-13-166

Curtis, PD, EM Quardokus, ML Lawler, X Guo, D Klein, JC Chen, RJ Arnold and YV Brun.  2012.  The scaffolding and signaling functions of a localization factor impact polar development.  Mol Micro.  84:712-35.  PMID: 22512778 PMCID: PMC3345042 DOI: 10.1111/j.1365-2958.2012.08055.x

Curtis, PD and YV Brun.  2010.  Getting in the loop:  regulation of development in Caulobacter crescentus.  Microbiol Mol Biol Rev.  74:13-41.  PMID: 20197497 PMCID: PMC2832345 DOI: 10.1128/MMBR.00040-09

Curtis, PD and YV Brun.  2010.  A novel effector protein modulates response regulator activity without altering phosphorylation.  Mol Cell. 39:319-20.  [Preview article].  PMID: 20705235 DOI: 10.1016/j.molcel.2010.07.034

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.  PMID: 17921303 PMCID: PMC2168639 DOI: 10.1128/JB.01008-07

Curtis, PD, J Atwood 3rd, R Orlando and LJ Shimkets.  2007.  Proteins associated with the Myxococcus xanthus extracellular matrix.  J Bacteriol.  189:7634-42.  PMID: 17766415 PMCID: PMC2168726 DOI: 10.1128/JB.01007-07

Curtis, PD, R Geyer, DC White and LJ Shimkets.  2006.  Novel lipids in Myxococcus xanthusand their role in chemotaxis.  Environ Microbiol.  8:1935-49.  PMID: 17014493 DOI: 10.1111/j.1462-2920.2006.01073.x

Curtis, P, CH Nakatsu and A Konopka.  2002.  Aciduric Proteobacteria isolated from pH 2.9 soil.  Arch Microbiol. 178:65-70.  PMID: 12070771 DOI: 10.1007/s00203-002-0427-1