Editing Salmonella (section)

=== Mechanisms of entry ===
Nontyphoidal serotypes preferentially enter [[Microfold cell|M cells]] on the intestinal wall by bacterial-mediated [[endocytosis]], a process associated with intestinal inflammation and diarrhoea. They are also able to disrupt [[tight junction]]s between the cells of the intestinal wall, impairing the cells' ability to stop the flow of [[ions]], water, and immune cells into and out of the intestine. The combination of the inflammation caused by bacterial-mediated endocytosis and the disruption of tight junctions is thought to contribute significantly to the induction of diarrhoea.<ref name=Haraga>{{cite journal | vauthors = Haraga A, Ohlson MB, Miller SI | title = Salmonellae interplay with host cells | journal = Nature Reviews. Microbiology | volume = 6 | issue = 1 | pages = 53–66 | date = January 2008 | pmid = 18026123 | doi = 10.1038/nrmicro1788 | s2cid = 2365666 }}</ref>

Salmonellae are also able to breach the intestinal barrier via [[phagocytosis]] and trafficking by [[CD18]]-positive immune cells, which may be a mechanism key to typhoidal ''Salmonella'' infection. This is thought to be a more stealthy way of passing the intestinal barrier, and may, therefore, contribute to the fact that lower numbers of typhoidal ''Salmonella'' are required for infection than nontyphoidal ''Salmonella''.<ref name=Haraga /> ''Salmonella'' cells are able to enter [[macrophage]]s via [[Macropinosome|macropinocytosis]].<ref>{{cite journal | vauthors = Kerr MC, Wang JT, Castro NA, Hamilton NA, Town L, Brown DL, Meunier FA, Brown NF, Stow JL, Teasdale RD | title = Inhibition of the PtdIns(5) kinase PIKfyve disrupts intracellular replication of Salmonella | journal = The EMBO Journal | volume = 29 | issue = 8 | pages = 1331–1347 | date = April 2010 | pmid = 20300065 | pmc = 2868569 | doi = 10.1038/emboj.2010.28 }}</ref> Typhoidal serotypes can use this to achieve dissemination throughout the body via the [[mononuclear phagocyte system]], a network of connective tissue that contains immune cells, and surrounds tissue associated with the immune system throughout the body.<ref name=Haraga />

Much of the success of ''Salmonella'' in causing infection is attributed to two [[type III secretion system]]s (T3SS) which are expressed at different times during the infection. The T3SS-1 enables the injection of bacterial effectors within the host cytosol. These T3SS-1 effectors stimulate the formation of membrane ruffles allowing the uptake of ''Salmonella'' by [[phagocytic cell|nonphagocytic cells]]. ''Salmonella'' further resides within a membrane-bound compartment called the ''Salmonella''-Containing Vacuole (SCV). The acidification of the SCV leads to the expression of the T3SS-2. The secretion of T3SS-2 effectors by ''Salmonella'' is required for its efficient survival in the host cytosol and establishment of systemic disease.<ref name=Haraga /> In addition, both T3SS are involved in the colonization of the intestine, induction of intestinal inflammatory responses and diarrhea. These systems contain many genes which must work cooperatively to achieve infection.{{citation needed|date=July 2020}}

The AvrA toxin injected by the SPI1 type III secretion system of ''S.'' Typhimurium works to inhibit the [[innate immune system]] by virtue of its [[serine]]/[[threonine]] [[acetyltransferase]] activity, and requires binding to [[Eukaryotic cell|eukaryotic]] target cell [[phytic acid]] (IP6).<ref name="PMID20430892">{{cite journal | vauthors = Mittal R, Peak-Chew SY, Sade RS, Vallis Y, McMahon HT | title = The acetyltransferase activity of the bacterial toxin YopJ of Yersinia is activated by eukaryotic host cell inositol hexakisphosphate | journal = The Journal of Biological Chemistry | volume = 285 | issue = 26 | pages = 19927–19934 | date = June 2010 | pmid = 20430892 | pmc = 2888404 | doi = 10.1074/jbc.M110.126581 | doi-access = free }}</ref> This leaves the host more susceptible to infection.{{citation needed|date=May 2021}}