This is a known issue with various flavours of El Capitan. It seems that 10.11 introduced some new USB stack, and as a result, people have been finding out that some of their USB devices just aren't being detected by the system at all in assorted versions of it. I don't use Calibre myself, but I've been unable to access my PlayBook and 3TB external drives via the Finder or the Terminal ever since the 10.11.4 upgrade while my other e-readers/drives worked just fine, and found out that this was apparently why when I tried to troubleshoot things.
Suggestions I came across which may or may not help you include
resetting the NVRAM and/or
the SMC on one's Mac. (I think resetting the NVRAM let one of my external drives show up for long enough for me to transfer some stuff on to it from 10.11.4, but then after I tried ejecting and reconnecting it, the problem came back.)
But the only thing that seems to consistently work seems to be to revert to whichever version of OS X was last working for you with regards to the affected devices.
Hope this helps, and welcome to MobileRead!