The U.S. Chamber of Commerce is threatening to run primary challenges against incumbent conservative members of the House of Representatives.

The Chamber has had it with conservatives mucking up their agenda on issues like immigration reform, the Export-Import Bank reauthorization, and highway spending, as Politico reported. The group is ready to start picking off troublemakers.

But the move is likely to backfire against corporate America’s voice in Washington, D.C., by inflaming grassroots conservatives. As much as the Republican base loathes big government, it despises big business profiting from the favors of big government almost as much. To many conservatives, that is exactly what the U.S. Chamber of Commerce represents.

The Republican brand will suffer as the bedrock of the party comes under assault from the Washington establishment.

Conservative leaders already are saying they will fight. David Bozell, president of ForAmerica, told the Heritage Foundation’s Daily Signal that “preserving” conservative lawmakers will be a priority for both his organization and the broader conservative community.

“If the Chamber of Commerce wants to pick a fight, the conservative movement is going to have to be ready, and I’m sure we will be,” Bozell said.

“If the Chamber of Commerce wants to pick a fight, then the conservative movement is going to have to be ready, and I’m sure we will be,” he said.

Dan Holler, communications director for Heritage Action, said, “If the Chamber of Commerce wants politicians in Washington that increase spending, shill for corporate welfare and enact sweeping amnesty, they should support Democrats.”

The sight of the Chamber pouring cash into GOP primary races in early 2016 is likely to galvanize conservatives just as they are being urged to the polls to choose a nominee for president.

The Chamber’s entrance into Republican internecine warfare would hurt the candidates viewed as closest to the trade group — most notably, former Florida Gov. Jeb Bush.

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In December, conservative columnist Michelle Malkin wrote a piece entitled, “Jeb Bush: The U.S. Chamber of Commerce’s Waterboy.” Columnist Marc Ambinder of The Atlantic and The Week described Bush as “a Chamber of Commerce conservative.” Last October, he cut political ads for the Chamber in Spanish.

No doubt Bush will be cringing during the primaries as some of the more conservative and populist candidates mercilessly tie him to an organization busy trying to rob the GOP base of representatives in Congress.

No doubt Bush will be cringing during the primaries as some of the more conservative and populist candidates mercilessly tie him to an organization busy trying to rob the GOP base of its representatives in Congress.

Sen. Ted Cruz of Texas, the candidate the Chamber can least stand the sight of, will be perfectly positioned to use the Chamber’s fratricidal push as part of his strategy of running against Washington.

Cruz indirectly derided the Chamber just last Friday during his appearance on the Senate floor, castigating Senate Republicans for listening “to one and only one voice: That is the voice of the Washington cartel, of the lobbyists on K Street, of the big money and big corporations.”

The feeling is mutual. In October 2013, after Cruz helped shut down the government over Obamacare, Chamber of Commerce President Tom Donahue was asked if having Cruz “sit down and shut up” is something he might want to arrange.

“Well, that might be one thing we could work on,” Donohue quipped.

Having the Chamber to kick around might be enticing to other populists in the race, as well as low single-digit candidates who need an issue, or even Donald Trump, who seems willing to fire away at any moving object.

By recklessly declaring war on the GOP’s most motivated voters, the Chamber threatens to demoralize and alienate the one faction of the party that is indispensable for achieving Republican victories in 2016.