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The twin brothers allegedly were living the drug trafficker’s dream, operating a lucrative distribution network in Chicago for not one but two Mexican cartels, seemingly well-positioned where tons of cocaine and heroin from south of the border are turned into stacks of cash on the city streets.

But it wouldn’t last.

When the cartels began a blood feud in Mexico last year, both warring factions told distributors including Pedro and Margarito Flores that they had better be loyal — or else.

The brothers, 28, instead began dealing with investigators, according to sources and court records, their cooperation becoming a centerpiece in what federal officials called the most significant drug case of its kind in Chicago history.

In a clear sign that the deadly reach of Mexican drug traffickers extends deep into America’s heartland, federal prosecutors in Washington and Chicago announced indictments against more than three dozen people, including a trio of international kingpins who had put the Flores brothers between a rock and a hard place. Among them was Joaquin “el Chapo” Guzman-Loera, a billionaire with a $5 million price on his head who has threatened violence inside the U.S.

The brothers were a cog in an international network both high-tech and simple, authorities said. Mexican cartel leaders armed with satellite phones used 747s and even a submarine to bring cocaine from South America to Mexico. Once the drugs got to Illinois, the two distributors here allegedly set up stash facilities all over Chicago and the suburbs while transporting their narcotics around the U.S. in vehicles with hidden compartments.

“With hundreds of millions of dollars going in the other direction,” U.S. Atty. Patrick Fitzgerald said as the indictments were announced.

The indictments come as U.S. authorities reinforce warnings that drug-related violence in Mexico, which has already claimed about 4,400 lives this year, threatens to spill over onto American soil as drug cartels fight over lucrative distribution routes and markets. The Obama administration has sent several Cabinet members to Mexico and pledged nearly $500 million to provide technology and training to Mexican law enforcement.

“These cartels are not abstract organizations operating in far-off places. They are multi-billion dollar networks funneling drugs onto our streets,” U.S. Atty. Gen. Eric Holder said at a news conference in Washington. “The audacity of the cartels’ operations is matched only by their sophistication and their reach.”

In all, 43 people were charged in a string of indictments in Chicago and New York, including 16 people in the Flores organization that ran drugs here for the cartels beginning in 2005. The government is seeking forfeiture of more than $5 billion in cash and property.

Other cartel leaders charged were Ismael “el Mayo” Zambada-Garcia, who is Guzman-Loera’s partner in the Sinaloa cartel, as well as Arturo Beltran-Leyva, who allegedly is running the group that split from the original alliance known as “the Federation.”

The indictments in Chicago and New York allege that between 1990 and 2008, the cartels in the case distributed nearly 200 metric tons of cocaine and heroin. And Chicago has remained a key location for the organizations, prosecutors said, alleging in the indictments that the Flores group repackaged cocaine for wholesale customers from Philadelphia to Vancouver

At a news briefing in Chicago, prosecutors declined to comment on any help the Flores brothers may have given investigators. Court documents in related cases suggest the brothers are being protected, but prosecutors declined to provide a date they went into custody.

Stephen Meiners, tactical analyst for Latin America at STRATFOR, a Texas-based global intelligence company, said there is a risk that the arrest of the Flores brothers might lead to a violent battle for control of the Chicago distribution network. Chicago police say they have noticed no uptick in drug-related violence connected with the arrests.

Meiners said Chicago is a natural hub for Mexican traffickers because of its central geography and necessary infrastructure, such as the warehouses and highways that the Flores twins allegedly utilized for distribution. Traffickers like working in areas with high Mexican populations because they then have the ability to exert control over their foot soldiers in the U.S. by threatening relatives back in Mexico, he said.

“I think it’s almost inevitable that we’re going to see escalation on both sides of the border,” Meiners said.