Editing Periplasm (section)

== Clinical significance ==
As bacteria are the responsible pathogen for many infections and illnesses, the biochemical and structural components that distinguish disease causing bacterial cells from native eukaryotic cells are of great interest from a clinical perspective.<ref>{{cite journal | vauthors = Prestinaci F, Pezzotti P, Pantosti A | title = Antimicrobial resistance: a global multifaceted phenomenon | journal = Pathogens and Global Health | volume = 109 | issue = 7 | pages = 309–318 | date = 2015-10-03 | pmid = 26343252 | pmc = 4768623 | doi = 10.1179/2047773215Y.0000000030 }}</ref> Gram-negative bacteria tend to be more [[Antimicrobial resistance|antimicrobial resistant]] than gram-positive bacteria, and also possess a much more significant periplasmic space between their two membrane bilayers. Since [[Eukaryote|eukaryotes]] do not possess a periplasmic space, structures and enzymes found in the gram-negative periplasm are attractive targets for antimicrobial drug therapies.<ref>{{cite journal | vauthors = Pandeya A, Ojo I, Alegun O, Wei Y | title = Periplasmic Targets for the Development of Effective Antimicrobials against Gram-Negative Bacteria | journal = ACS Infectious Diseases | volume = 6 | issue = 9 | pages = 2337–2354 | date = September 2020 | pmid = 32786281 | pmc = 8187054 | doi = 10.1021/acsinfecdis.0c00384 }}</ref> Additionally, vital functions such as facilitation of protein folding, protein transport, cell signaling, structural integrity, and nutrient uptake are performed by periplasm components,<ref name="Miller_2018" /> making it rich in potential drug targets. Aside from [[Enzyme|enzymes]] and structural components that are vital to cell function and survival, the periplasm also contains virulence-associated proteins such as DsbA that can be targeted by antimicrobial therapies.<ref>{{cite journal | vauthors = Ha UH, Wang Y, Jin S | title = DsbA of Pseudomonas aeruginosa is essential for multiple virulence factors | journal = Infection and Immunity | volume = 71 | issue = 3 | pages = 1590–1595 | date = March 2003 | pmid = 12595484 | pmc = 148828 | doi = 10.1128/IAI.71.3.1590-1595.2003 }}</ref> Due to their role in catalyzing disulfide bond formation for a variety of virulence factors, the DsbA/DsbB system has been of particular interest as a target for anti-virulence drugs.<ref>{{cite journal | vauthors = Smith RP, Paxman JJ, Scanlon MJ, Heras B | title = Targeting Bacterial Dsb Proteins for the Development of Anti-Virulence Agents | journal = Molecules | volume = 21 | issue = 7 | pages = 811 | date = July 2016 | pmid = 27438817 | pmc = 6273893 | doi = 10.3390/molecules21070811 | doi-access = free }}</ref>

The periplasmic space is deeply interconnected with the pathogenesis of disease in the setting of microbial infection. Many of the [[Virulence factor|virulence factors]] associated with bacterial pathogenicity are secretion proteins, which are often subject to post-translational modification including disulfide bond formation.<ref name="Łasica_2007">{{cite journal | vauthors = Łasica AM, Jagusztyn-Krynicka EK | title = The role of Dsb proteins of Gram-negative bacteria in the process of pathogenesis | journal = FEMS Microbiology Reviews | volume = 31 | issue = 5 | pages = 626–636 | date = September 2007 | pmid = 17696887 | doi = 10.1111/j.1574-6976.2007.00081.x | doi-access = free }}</ref> The oxidative environment of the periplasm contains Dsb (disulfide bond formation) proteins that catalyze such post-translational modifications, and therefore play an important role in establishing virulence factor tertiary and quaternary structure essential for proper protein function.<ref name="Łasica_2007" /> In addition to Dsb proteins found in the periplasm, motility organelles such as the flagellum are also essential for host infection. The flagellum is rooted in the periplasm and is stabilized by interaction with periplasmic structural components,<ref name="Miller_2018" /><ref name="Łasica_2007" /> and is therefore another pathogenesis-related target for antimicrobial agents. During infection of a host, the cell of a bacterium is subject to many turbulent environmental conditions, which highlights the importance of the structural integrity afforded by the periplasm. In particular, peptidoglycan synthesis is vital to cell wall production, and inhibitors of peptidoglycan synthesis have been of clinical interest for targeting bacteria for many decades.<ref>{{cite journal | vauthors = Puls JS, Brajtenbach D, Schneider T, Kubitscheck U, Grein F | title = Inhibition of peptidoglycan synthesis is sufficient for total arrest of staphylococcal cell division | journal = Science Advances | volume = 9 | issue = 12 | pages = eade9023 | date = March 2023 | pmid = 36947615 | pmc = 10032595 | doi = 10.1126/sciadv.ade9023 | bibcode = 2023SciA....9E9023P }}</ref><ref>{{cite journal | vauthors = Linnett PE, Strominger JL | title = Additional antibiotic inhibitors of peptidoglycan synthesis | journal = Antimicrobial Agents and Chemotherapy | volume = 4 | issue = 3 | pages = 231–236 | date = September 1973 | pmid = 4202341 | pmc = 444534 | doi = 10.1128/AAC.4.3.231 }}</ref> Furthermore, the periplasm is also relevant to clinical developments by way of its role in mediating the uptake of [[Transformation (genetics)|transforming DNA]].<ref name="Hahn_2021" />