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Billionaire philanthropist Betsy DeVos' bid to be President Donald Trump's Secretary of Education could be in jeopardy after two Republican senators announced Wednesday that they'll vote against confirming her for the job.

Sen. Susan Collins of Maine and Sen. Lisa Murkowski of Alaska both said they cannot support DeVos, a fierce advocate for charter schools and voucher programs as well a prolific donor to Republican causes.

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Republican leaders have been racing to shore up support for the nominee and soon after Collins and Murkowski's announcements GOP Sen. Dean Heller of Nevada said that he will back her confirmation, calling her "the right choice for this position."

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The next procedural vote on her nomination is now expected on Friday.

The White House expressed confidence Wednesday afternoon that DeVos will ultimately be confirmed, despite the defections.

But it'll be close. Republicans hold a narrow 52-seat majority in the Senate. Without Collins and Murkowski, DeVos' nomination faces a 50-50 deadlocked Senate — confirmation requires a simple majority.

If the current vote count holds, it would set up an unprecedented tie-breaking vote by Vice President Mike Pence. A vice president has never cast a tying vote on a cabinet nomination, according to the Senate Historian's office.

The close vote will also prove to be a slight complication to the confirmation of GOP Sen. Jeff Sessions as attorney general. His confirmation vote will need to be scheduled after DeVos’ since his vote will be needed to approve her.

Related: Betsy DeVos Cites Grizzly Bears During Guns-in-Schools Debate

Democrat Joe Manchin of West Virginia, who has been supportive of several of Trump's other Cabinet picks, announced earlier Wednesday that he will not vote for DeVos.

“Betsy DeVos has never attended or worked in a public school," he said. "The needs facing rural schools in West Virginia are unique, and her lack of exposure to public education is very concerning for me."

While many Democrats were already opposed to her push for voucher programs and charter schools, her bid to lead the education department was further damaged during her confirmation hearing, when DeVos appeared to be unfamiliar with the basics of federal special education law.

DeVos was also ridiculed for responding to a question about guns in schools by referencing the possibility that a grizzly bear could appear at a school building in Wyoming.

"I would imagine there is probably a gun in a school to protect from potential grizzlies," she said.