In my mind, there are two major barriers to any future Class I consolidation: shippers and the rules; however, I don't think these are insurmountable.
One of the many reasons why CP-CSX and CP-NS failed was the near-total lack of shipper support. The combination of poor service under PSR and the slow rise in rates has made shippers weary of any large-scale consolidation. However, as railroads continue to shed PSR and focus more on customer service, I think you'll begin to see the attitude toward large-scale consolidation change. In fact, you've already seen it to a certain degree. Shipper support for smaller consolidations such as CSX-PAR and CP-KCS has been far, far greater than for CP-CSX and CP-NS. Heck, an often-forgotten fact about the whole CN-CP-KCS battle was that CN-KCS actually had more shipper support than CP-KCS!
The current Class I merger rules state that any merger must expand competition and not just keep it as-is. This is a high hurdle to cross, as shown by the CN-KCS merger attempt. (KCS was the only railroad exempt from the rules, but CN foolishly decided to have the merger judged under the new ones.) Any Class I merger would have to include a degree of open access and loads of trackage rights as concessions.
All of this being said, I still think we're 5-10 years off from any Class I merger not facing a large amount of opposition.
Mexcio is interesting. BNSF has not been quiet about their desire to expand south of the border, even trying to gain direct access to Laredo as a concession of CPKC. There are the Isthmus and Maya projects which could go up for grabs once they are completed.
I think in the near term you'll continue to see the remaining independent medium-to-large regional railroads be eaten up by the Class Is. One factor that the CMQ, PAR, MRL, and KCS all had in common is that they were decent-sized railroads that weren't a part of any large holding company like G&W or WATCO. FEC being owned by Grupo Mexico is safe.
I too am curious as to what happened the the "great CSX garage sale" back in 2018.
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