"Great to see that Dr. Kelli Ward is running against Flake Jeff Flake, who is WEAK on borders, crime and a non-factor in Senate. He's toxic!" Trump tweeted.
Flake's team shot back in a statement issued later Thursday morning: "You don't serve Arizona by cutting backroom deals in Washington, D.C. That's why Senator Flake will always fight for the people of our state."
Flake's senior Arizona colleague, Sen. John McCain, also came to his defense on Twitter, apparently in response to Trump's tweet:
".@JeffFlake is a principled legislator & always does what's right for the people of #AZ. Our state needs his leadership now more than ever," McCain wrote.
And Colorado Sen. Cory Gardner, who chairs the National Republican Senatorial Committee, also defended Flake, saying the group "unequivocally supports" the Arizona senator.
Ward responded to the President's message, writing back, "Thank you @realDonaldTrump Working hard so you have a conservative from AZ to help #MAGA. Arizonans excited to see you again next week!"
Ward, an osteopathic physician and former Arizona state senator, is challenging Flake in Arizona's 2018 Republican primary after having failed to unseat McCain in the previous primary cycle. Flake, meanwhile, has emerged as a regular Trump antagonist in Congress and one of his party's loudest critical voices of the commander in chief.
Flake recently kicked off his re-election campaign
with the release of a book, "The Conscience of a Conservative," in which Flake unloads on Trump and condemns his party for enabling Trump's rise to power.
In the book, the Arizona Republican details a long-running feud with Trump that dates back to Flake's resistance, early on, to Trump's presidential campaign. He writes critically about Trump's campaign, calling it "free of significant thought" and compares it to a "late-night infomercial." Flake also touches on Trump's own prediction that their differences would cost Flake his seat.
"You've been very critical of me," Trump told him in a summer 2016 meeting recounted in the book.
"In the tweeting life of our president, strategy is difficult to detect. Influencing the news cycles seems to be the principal goal; achieving short-term tactical advantage, you bet. But ultimately, it's all noise and no signal," Flake writes.
Flake had also called on Trump to withdraw from the presidential race after the release of the "Access Hollywood" tape, which showed Trump making lewd comments about women.
Ward told CNN in July that she had talked to White House officials about her run against the incumbent Flake. She also controversially suggested that McCain might need to step down
from his seat after his brain cancer diagnosis last month -- which would have opened the door to her potential appointment to his seat.
Trump, meanwhile, plans to hold a rally in Phoenix, Arizona, next week, where he'll have another chance to wade into the state's turbulent Republican politics.