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Directing the movement of a pathogen
The opportunistic pathogen Pseudomonas aeruginosa is particularly resistant to antibiotic treatment when it forms biofilms on surfaces, such as in lungs or on medical equipment. The formation of P. aeruginosa biofilms requires both random and directed migration, and the bacterial messenger cyclic diguanylate monophosphate (c-di-GMP) is critical for all of these processes. Xu et al. (see also Orr and Lee) found that binding of c-di-GMP to the adaptor protein MapZ suppressed frequent changes in direction (which enables constant adjustment to changing conditions), attachment to surfaces, and biofilm formation by P. aeruginosa. These results suggest that the MapZ-associated chemotaxis pathway could be targeted to prevent the chronic and hard-to-treat infections caused by P. aeruginosa.
The bacterial messenger cyclic diguanylate monophosphate (c-di-GMP) binds to various effectors, the most common of which are single-domain PilZ proteins. These c-di-GMP effectors control various cellular functions and multicellular behaviors at the transcriptional or posttranslational level. We found that MapZ (methyltransferase-associated PilZ; formerly known as PA4608), a single-domain PilZ protein from the opportunistic pathogen Pseudomonas aeruginosa, directly interacted with the methyltransferase CheR1 and that this interaction was enhanced by c-di-GMP. In vitro assays indicated that, in the presence of c-di-GMP, MapZ inhibited CheR1 from methylating the chemoreceptor PctA, which would be expected to increase its affinity for chemoattractants and promote chemotaxis. MapZ localized to the poles of P. aeruginosa cells, where the flagellar motor and other chemotactic proteins, including PctA and CheR1, are also located. P. aeruginosa cells exhibit a random walk behavior by frequently switching the direction of flagellar rotation in a uniform solution. We showed that binding of c-di-GMP to MapZ decreased the frequency of flagellar motor switching and that MapZ was essential for generating the heterogeneous motility typical of P. aeruginosa cell populations and for efficient surface attachment during biofilm formation. Collectively, the studies revealed that c-di-GMP affects flagellar motor output by regulating the methylation of chemoreceptors through a single-domain PilZ adaptor protein.