I am using Kayako's help desk - one of the most popular PHP based helpdesks. Installing WP MU in the root directory causes a direct conflict:
The WP MU htaccess file contains the following:
RewriteRule ^(.*/)?files/$ index.php [L]
RewriteCond %{REQUEST_URI} !.*wp-content/plugins.*
RewriteRule ^(.*/)?files/(.*) wp-content/blogs.php?file=$2 [L]
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The problem is that in the Kayako directory there is a directory called "files." In fact, in many scripts there are directories called "files." This htaccess command will cause access problems in all the other subdirectories apparently. Is anyone more familiar with this area that might suggest a better workaround for WP MU?