The first response of bacteria to a noxious agent such as an antibiotic is the induced over expression of efflux pumps. Once the threat of the noxious agent passes, the level of efflux pump expression returns to its normal baseline.
Material secreted by bacteria such as those involved in quorum sensing (QS) and biofilm take place via the efflux pump system of the bacterium (Varga ZG, Armada A, Cerca P, Amaral L, Mior Ahmad Subki MA, Savka MA, Szegedi E, Kawase M, Motohashi N, Molnár J. Inhibition of quorum sensing and efflux pump system by trifluoromethyl ketone proton pump inhibitors. In Vivo. 2012). Because diffusion of other materials does not take place readily across the plasma membrane or outer membrane of bacteria, the means by which these materials (toxins, inducers, inhibitors, etc) are secreted may represent targets that may be exploited for the therapy of infections whose success lies in the materials secreted.
I would like for the members of RG to present their views on this subject for the purpose of expanding the possibility of new targets to be exploited, especially for the therapy of Gram-negative infections.
Secretion could also be performed by the release of outer membrane vesicles (OMV) allowing discharge of membrane/peptidoglycan components, or protective transportation/secretion of e.g. toxins or other functional proteins
Dear Sir
Efflux pumps are compartments really important in bacterial secretion. But as a microbiologist, I think that it is not all of the story and there are some other ways by which the material can be secreted.
Gram-negative bacteria have numerous secretion systems that are important in pathogenesis. There are types I-VII secretion systems and many Gram-negative pathogens have several of these systems. There are many companies that are currently designing drugs/antibodies that bind to the type III secretion system and render bacteria such as P. aeruginosa avirulent. Blocking bacterial secretion is definitely a viable means to cure many bacterial diseases.
Dear Zachary, The secretory products from Type III secretory system need to escape from the periplasm of the cell and they probably do so via the main RND efflux pump of the Gram-negative bacterium. Although hardly any work in this area has yet to be realized, here are two important references that show the relationship between efflux pump and type III secretion system (Webber MA, Bailey AM, Blair JM, Morgan E, Stevens MP, Hinton JC, Ivens A, Wain J, Piddock LJ. The global consequence of disruption of the AcrAB-TolC efflux pump in Salmonella enterica includes reduced expression of SPI-1 and other attributes required to infect the host. J Bacteriol. 2009 Jul;191(13):4276-85. doi:10.1128/JB.00363-09. Epub 2009 May 1. PubMed PMID: 19411325; PubMed CentralPMCID: PMC2698494:
Brown DG, Swanson JK, Allen C. Two host-induced Ralstonia solanacearum genes,
acrA and dinF, encode multidrug efflux pumps and contribute to bacterial wilt
virulence. Appl Environ Microbiol. 2007 May;73(9):2777-86. Epub 2007 Mar 2.
PubMed PMID: 17337552; PubMed Central PMCID: PMC1892870.).
The secreted compounds are removed via the efflux pump from the periplasm (see Seeger MA, Diederichs K, Eicher T, Brandstätter L, Schiefner A, Verrey F, Pos KM. The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance. Curr Drug Targets. 2008 Sep;9(9):729-49. Review. PubMed PMID: 18781920.).
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