Editing Treponema pallidum (section)

==== Outer membrane ====
The outer membrane (OM) of ''T. pallidum'' has several features that have made it historically difficult to research. These include details such as its low protein content, its fragility, and that it contains fewer gene sequences related to other gram negative outer membranes.<ref name="Radolf-2018">{{Cite book |last1=Radolf |first1=Justin D. |last2=Kumar |first2=Sanjiv |title=Spirochete Biology: The Post Genomic Era |chapter=The ''Treponema pallidum'' Outer Membrane |series=Current Topics in Microbiology and Immunology |date=2018 |volume=415 |pages=1–38 |doi=10.1007/82_2017_44 |issn=0070-217X |pmc=5924592 |pmid=28849315|isbn=978-3-319-89637-3 }}</ref> Progress has been made using genomic sequencing and advanced computational models. The treponemal outer membrane proteins are key factors for the bacterium's pathogenesis, persistence, and immune evasion strategies. The relatively low protein content prevents antigen recognition by the immune system and the proteins that do exist protrude out of the OM, enabling its interaction with the host.<ref name="Radolf-2018" /> ''Treponema's'' reputation as a "stealth pathogen" is primarily due to this unique OM structure, which serves to evade immune detection.<ref name="Radolf-2018"/>

=====TP0126=====

The TP0126 protein has been linked to the outer membrane protein family (OMP). This protein will sit in the outer membrane like a [[Porin (protein)|porin]], which is supported by [[circular dichroism]] recombinant TP0126, and will increase the virulence factor.<ref name=":2">{{Cite journal |last1=Giacani |first1=Lorenzo |last2=Brandt |first2=Stephanie L. |last3=Ke |first3=Wujian |last4=Reid |first4=Tara B. |last5=Molini |first5=Barbara J. |last6=Iverson-Cabral |first6=Stefanie |last7=Ciccarese |first7=Giulia |last8=Drago |first8=Francesco |last9=Lukehart |first9=Sheila A. |last10=Centurion-Lara |first10=Arturo |date=June 2015 |title=Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat |journal=Infection and Immunity |volume=83 |issue=6 |pages=2275–2289 |doi=10.1128/IAI.00360-15 |issn=1098-5522 |pmc=4432754 |pmid=25802057}}</ref> Researchers have classified the TP0126 protein in this class due to the homology between the protein and the porins of the OMPs.<ref name=":3">{{Cite journal |last1=Haynes |first1=Austin M. |last2=Godornes |first2=Charmie |last3=Ke |first3=Wujian |last4=Giacani |first4=Lorenzo |date=August 2019 |title=Evaluation of the Protective Ability of the Treponema pallidum subsp. pallidum Tp0126 OmpW Homolog in the Rabbit Model of Syphilis |journal=Infection and Immunity |volume=87 |issue=8 |pages=e00323–19 |doi=10.1128/IAI.00323-19 |issn=1098-5522 |pmc=6652746 |pmid=31182617}}</ref><ref name=":2" /> This protein is encoded by the tp0126 gene, which is conserved over all strains of ''T. pallidum.'' <ref name=":3" />

===== TP0326 =====
TP0326 is an [[Sequence homology|ortholog]] of the β-barrel assembly machine [[Bam A]]. BamA apparatus  inserts newly synthetized and exported outer membrane proteins into the outer membrane.<ref name="Hawley-2021">{{Cite journal |last1=Hawley |first1=Kelly L. |last2=Montezuma-Rusca |first2=Jairo M. |last3=Delgado |first3=Kristina N. |last4=Singh |first4=Navreeta |last5=Uversky |first5=Vladimir N. |last6=Caimano |first6=Melissa J. |last7=Radolf |first7=Justin D. |last8=Luthra |first8=Amit |date=8 July 2021 |editor-last=Galperin |editor-first=Michael Y. |title=Structural Modeling of the ''Treponema pallidum'' Outer Membrane Protein Repertoire: a Road Map for Deconvolution of Syphilis Pathogenesis and Development of a Syphilis Vaccine |journal=Journal of Bacteriology |language=en |volume=203 |issue=15 |pages=e0008221 |doi=10.1128/JB.00082-21  |pmc=8407342 |pmid=33972353}}</ref>

===== TP0453 =====
TP0453 is a 287 amino acid protein associated with the inner membrane of the microbe's outer membrane.<ref name="Chen22">{{Cite journal |last1=Chen |first1=Jinlin |last2=Huang |first2=Jielite |last3=Liu |first3=Zhuoran |last4=Xie |first4=Yafeng |date=27 September 2022 |title=''Treponema pallidum'' outer membrane proteins: current status and prospects |journal=Pathogens and Disease |language=en |volume=80 |issue=1 |doi=10.1093/femspd/ftac023 |pmid=35869970 |doi-access=free}}</ref> This protein lacks the extensive [[beta sheet]] structure that is characteristic of other membrane proteins, and does not traverse the outer membrane.<ref>{{Cite journal |last1=Hazlett |first1=Karsten R. O. |last2=Cox |first2=David L. |last3=Decaffmeyer |first3=Marc |last4=Bennett |first4=Michael P. |last5=Desrosiers |first5=Daniel C. |last6=La Vake |first6=Carson J. |last7=La Vake |first7=Morgan E. |last8=Bourell |first8=Kenneth W. |last9=Robinson |first9=Esther J. |last10=Brasseur |first10=Robert |last11=Radolf |first11=Justin D. |date=September 2005 |title=TP0453, a concealed outer membrane protein of ''Treponema pallidum'', enhances membrane permeability |journal=Journal of Bacteriology |volume=187 |issue=18 |pages=6499–6508 |doi=10.1128/JB.187.18.6499-6508.2005  |pmc=1236642 |pmid=16159783}}</ref> This protein's function has been hypothesized to be involved with control of nutrient uptake.<ref>{{Cite journal |last1=Luthra |first1=Amit |last2=Zhu |first2=Guangyu |last3=Desrosiers |first3=Daniel C. |last4=Eggers |first4=Christian H. |last5=Mulay |first5=Vishwaroop |last6=Anand |first6=Arvind |last7=McArthur |first7=Fiona A. |last8=Romano |first8=Fabian B. |last9=Caimano |first9=Melissa J. |last10=Heuck |first10=Alejandro P. |last11=Malkowski |first11=Michael G. |last12=Radolf |first12=Justin D. |date=2 December 2011 |title=The transition from closed to open conformation of ''Treponema pallidum'' outer membrane-associated lipoprotein TP0453 involves membrane sensing and integration by two amphipathic helices |journal=The Journal of Biological Chemistry |volume=286 |issue=48 |pages=41656–68 |doi=10.1074/jbc.M111.305284 |issn=1083-351X |pmc=3308875 |pmid=21965687 |doi-access=free }}</ref>

===== TP0624 =====
Outer Membrane Protein A (OmpA) domain-containing proteins are necessary for maintaining structural integrity in gram-negative bacteria. These domains contain peptidoglycan binding sites which creates a "structural bridge between the peptidoglycan layer and the outer memebrane."<ref name="Parker-2016">{{Cite journal |last1=Parker |first1=Michelle L. |last2=Houston |first2=Simon |last3=Wetherell |first3=Charmaine |last4=Cameron |first4=Caroline E. |last5=Boulanger |first5=Martin J. |date=10 November 2016 |title=The Structure of ''Treponema pallidum'' Tp0624 Reveals a Modular Assembly of Divergently Functionalized and Previously Uncharacterized Domains |journal=PLOS ONE |language=en |volume=11 |issue=11 |pages=e0166274 |doi=10.1371/journal.pone.0166274  |pmc=5104382 |pmid=27832149 |bibcode=2016PLoSO..1166274P |doi-access=free }}</ref> The protein TP0624 found in ''T.'' ''pallidum'' has been proposed to facilitate this structural link, as well as interactions between outer membrane proteins and corresponding domains on the thin [[peptidoglycan layer]].<ref name="Parker-2016" />

=====TP0751=====

The TP0751 protein is a protein that is unique to ''T. pallidum'', and it is thought to aid in attachment to the host's extra cellular membrane.<ref name=":02">{{Cite journal |last1=Parker |first1=Michelle L. |last2=Houston |first2=Simon |last3=Pětrošová |first3=Helena |last4=Lithgow |first4=Karen V. |last5=Hof |first5=Rebecca |last6=Wetherell |first6=Charmaine |last7=Kao |first7=Wei-Chien |last8=Lin |first8=Yi-Pin |last9=Moriarty |first9=Tara J. |last10=Ebady |first10=Rhodaba |last11=Cameron |first11=Caroline E. |last12=Boulanger |first12=Martin J. |date=September 2016 |title=The Structure of Treponema pallidum Tp0751 (Pallilysin) Reveals a Non-canonical Lipocalin Fold That Mediates Adhesion to Extracellular Matrix Components and Interactions with Host Cells |journal=PLOS Pathogens |volume=12 |issue=9 |pages=e1005919 |doi=10.1371/journal.ppat.1005919 |doi-access=free |issn=1553-7374 |pmc=5040251 |pmid=27683203}}</ref> Since this protein aids in the attachment to the host, it sits on the surface of the cells, and in 2005, it was discovered that the TP0751 protein will attach to the [[laminin]] component in the host's [[extracellular matrix]].<ref name=":12">{{Cite journal |last1=Cameron |first1=Caroline E. |last2=Brouwer |first2=Nathan L. |last3=Tisch |first3=Lisa M. |last4=Kuroiwa |first4=Janelle M. Y. |date=November 2005 |title=Defining the interaction of the Treponema pallidum adhesin Tp0751 with laminin |journal=Infection and Immunity |volume=73 |issue=11 |pages=7485–7494 |doi=10.1128/IAI.73.11.7485-7494.2005 |issn=0019-9567 |pmc=1273862 |pmid=16239550}}</ref> With that, it is thought that the TP0751 protein plays a key role in dissemination with the host.<ref name=":12" /><ref name=":02" />

===== TP0965 =====
TP0965 is a protein that is critical for membrane fusion in ''T. pallidum'', and is located in the [[periplasm]].<ref name="Chen22" /> TP0965 causes endothelial barrier dysfunction, a hallmark of late-stage pathogenesis of [[syphilis]].<ref>{{Cite journal |last1=McKevitt |first1=Matthew |last2=Brinkman |first2=Mary Beth |last3=McLoughlin |first3=Melanie |last4=Perez |first4=Carla |last5=Howell |first5=Jerrilyn K. |last6=Weinstock |first6=George M. |last7=Norris |first7=Steven J. |last8=Palzkill |first8=Timothy |date=July 2005 |title=Genome Scale Identification of ''Treponema pallidum'' Antigens |journal=Infection and Immunity |volume=73 |issue=7 |pages=4445–50 |doi=10.1128/iai.73.7.4445-4450.2005 |pmc=1168556 |pmid=15972547}}</ref> It does this by reducing the expression of tight junction proteins, which in turn increases the expression of adhesion molecules and endothelial cell permeability, which eventually leads to disruption of the [[Endothelium|endothelial]] layer.<ref>{{Cite journal |last1=Zhang |first1=Rui-Li |last2=Zhang |first2=Jing-Ping |last3=Wang |first3=Qian-Qiu |date=16 December 2014 |title=Recombinant ''Treponema pallidum'' Protein Tp0965 Activates Endothelial Cells and Increases the Permeability of Endothelial Cell Monolayer |journal=PLOS ONE |volume=9 |issue=12 |pages=e115134 |bibcode=2014PLoSO...9k5134Z |doi=10.1371/journal.pone.0115134 |pmc=4267829 |pmid=25514584 |doi-access=free}}</ref>