(CNN) The US-led coalition against ISIS waged a series of airstrikes against a military convoy of loyalists to the Syrian regime, CNN has confirmed.

This marks only the second time in the history of the six-year conflict that American warplanes have intentionally targeted Iranian proxies in Syria. The convoy appears to have consisted not of regular Syrian army soldiers but of international Shia militiamen.

According to a US defense official, a convoy of 20 pro-regime vehicles was headed toward al-Tanf, a military base on the Syrian-Jordanian border, on Wednesday night.

Al-Tanf, which Russian warplanes bombed a year ago in two successive airstrikes, is occupied by US and British Special Forces that are advising an anti-ISIS Syrian rebel group known as Maghawir al-Thawra, or the Commandos of the Revolution.

Thirteen of the vehicles apparently breached the "de-confliction zone" around the base, an area that the coalition has communicated to Moscow to stay well clear of.

US warplanes were first scrambled in a "show of force" against the oncoming convoy. But then five vehicles kept approaching, coming within 29 kilometers of the base when they were finally hit by US aircraft.

The coalition confirmed that the convoy posed a direct threat to "US partner forces" -- "despite Russian attempts to dissuade pro-regime movement" toward the base.

The strike marks the first time that the Pentagon has offered aerial protection to its Arab proxies under assault from pro-Syrian militias.

The timing of this American escalation is noteworthy for several reasons.

First, it comes just weeks after US warships in the Mediterranean fired 59 Tomahawk cruise missiles against Assad's Shayrat airbase, which Western intelligence agencies allege was used to launch a deadly chemical weapons attack in northern Syria. That intervention was the first time the US directly attacked the Syrian government.

Second, the al-Tanf skirmish comes just hours after President Donald Trump is scheduled to depart Washington for a tour of the Middle East, his first overseas trip since assuming office. He will travel to Jerusalem and Riyadh, Saudi Arabia where he is expected to reassure Israel and America's Sunni Gulf allies that his administration is committed to containing and deterring Iran, now the principal security underwriter of the Assad regime in Syria.

Third, the US Treasury Department on Wednesday sanctioned two senior Iranian officials, one of whom, the department said in a press statement, "facilitated the sale of explosives and provided other support to Syria." The other was "the director of the organization responsible for Iran's solid-fueled ballistic missile program."

Fourth, the US airstrikes follow on a State Department briefing about the presence of a crematorium for incinerating corpses of political prisoners at the notorious Sednaya jail in Damascus. Allegations about such a facility, reminiscent of the Third Reich's Final Solution, have circulated in international media for months, yet the US government only just confirmed them this week.

Containing Iran

Iran is thought to have expansionist ambitions, and these ambitions have begun to chafe under a slowly increasing US hard power deployment in the region, opposition sources have told CNN.

Tlass Salameh, the commander of the Lions of the East Brigade, said that his men are located 20 kilometers from al-Tanf. The Lions of the East receive support from a covert CIA program designed to train and arm vetted Syrian rebel groups, according to Salameh.

Recruits of that program are allowed to fight the Syrian regime and its allied militias, including those imported from Lebanon and Iraq and beholden to Iran's Revolutionary Guards Corps' Quds Force.

On Monday, Iran's state-run Fars News Agency claimed that Lebanese Hezbollah, a prominent IRGC-QC proxy, had deployed "12 regiments with 1,000 fighters" to southern Syria "to face the US-backed militants in al-Tanf border crossing."

"The regime is bombing us in 25 to 30 raids on a daily basis. Russia hit us once or twice," Salameh told CNN. "We have a post in Mafraq Kabid on the Damascus-Baghdad highway, which is now controlled by the Iranian and [Lebanese] Hezbollah militias."

That transnational highway is crucial to Iranian plans to construct a ground corridor, or land bridge, from Tehran all the way to Mediterranean coast.

Rebel sources confirm a report published this week by Britain's Guardian newspaper to that effect, noting that the original route for this corridor has recently shifted from northern Syria, running through the heartland of Syrian Kurdish territory, to Sunni Arab tribal south of the country. The outlet suggested that the change of latitude owed to a growing presence of US troops and US-run military installations the north, used by various anti-ISIS forces.

Partition of Syria

Concerns over the long-term implications of the US presence, for example, led the regime to oppose an expanded role for the Syrian opposition in the fight against ISIS, especially in Raqqa, the terror group's de facto capital.

Now, sources say, Damascus and Tehran are keen to preempt any such American deterrent in the south, along the new route for a land bridge — even if doing so slows or retards the coalition's war against ISIS.

"The regime is preventing us from fighting ISIS," Salameh said. "Not a single attack waged by them is directed against ISIS, even though ISIS is only 20 kilometers meters away from the regime while we are 80 kilometers away."

Salameh added that Iranian-built militias have lately reconquered terrain liberated from ISIS by the coalition and the Lions of the East.

Muhannad al-Talla, commander of Maghawir al-Thawrah, the Pentagon-backed rebel group embedded with US and British Special Forces at al-Tanf, agreed with this assessment, and with the idea of an Iranian ground corridor.

"The Russians, the Iranians and the regime are harassing us now. After we liberated some areas, they came and took them," al-Talla said. "They're trying to open the highway from Baghdad to Damascus, in other words from Tehran to Beirut. They are advancing toward us and toward eastern Syria. This has been happening for two weeks now."

Some policymakers the US and Syria believe that a deal to create "de-escalation zones," brokered in Astana, Kazakhstan earlier this month by Russia, Iran and Turkey, was designed to preempt any American plan to unilaterally establish safe zones in Syria.

In March, Secretary of State Rex Tillerson said Washington would set up "interim zones of stability" to allow refugees to return to Syria.

Officials in the US State Department have told CNN that the terminology used by Russia in Astana deliberately echoed Tillerson's position. Some Middle East analysts have argued that the long-term consequence of such a policy — establishing externally-enforced zones, if not spheres of influence — amounts to the soft partitioning of Syria.

According to Reuters, citing Western intelligence sources, American and British Special Forces are building out al-Tanf to encompass a larger role in flushing ISIS out of the eastern Syrian province of Deir Ezzor. So a similar enlargement of the US garrison in the south is indeed likely.

At the same time, the Assad regime has also become more publicly critical of Jordan, a key Arab member of the anti-ISIS coalition, owing to reports that the Jordanian army was mobilizing near the Syrian border.

Jordan oversees two large refugee camps inside Syria which host displaced people from areas previously or currently controlled by ISIS, making them a ongoing security concern for the Hashemite kingdom. A safe zone near the Syrian-Jordanian border, backed by Arab and western powers, is clearly viewed as a provocation to Damascus and Tehran.

The tension between the regime and Amman in recent weeks came after unprecedented remarks from Jordanian authorities that Jordan would open its border crossings with Syria if the regime, not the rebels, controlled the borderlands, over fears that al Qaeda and ISIS jihadists will cross into Jordan.

The de-escalation zones are also believed, by US and opposition sources, to free up time and resources for the regime to advance into the American sphere of influence in ISIS areas.

The Syrian regime and Iran probably calculated that the US would not come to the aid of its rebel allies in al-Tanf, as it untraditionally did on Wednesday.

In fact, al-Talla, the commander of Maghawir al-Thawrah, said, a day before the airstrikes he was told by US forces that his men would be relocated from al-Tanf to another position in Syria to avoid open conflict with pro-Assad elements.

That plan may have now changed.