The future of Malta’s prime minister, Joseph Muscat, hangs in the balance after his chief of staff and two ministers stepped down in rapid succession amid controversy over the murder of the anti-corruption journalist Daphne Caruana Galizia.

The ministerial departures on Tuesday followed a series of arrests in the hunt for those behind the assassination of Caruana Galizia, a renowned investigative reporter who was killed by a car bomb near her home in October 2017.

The resignations of the chief of staff, Keith Schembri, and the tourism minister, Konrad Mizzi, were immediately followed by an announcement that the economy minister, Chris Cardona, was suspending himself. All three men have denied wrongdoing.

The departures came almost four years after Caruana Galizia used a leak of offshore information, known as the Panama Papers, to reveal that Schembri and Mizzi, who was then energy minister, had become the beneficiaries of secretive Panama shell companies shortly after assuming office.

Quick guide Daphne Caruana Galizia investigation: who's who Show Hide Daphne Caruana Galizia Malta's best-known investigative journalist was killed in a car bomb as she left her home in October 2017. Alfred Degiorgio, George Degiorgio and Vincent Muscat Three men in their fifties arrested in December 2017 and then formally charged in July 2019 with Caruana Galizia’s murder, criminal conspiracy and the criminal use of explosives. Melvin Theuma A taxi driver from Birkirkara and suspected middleman in the Caruana Galizia case, he was arrested on 14 November 2019 in a separate money laundering case. He has offered to provide information he says he has on the journalist's death in exchange for a pardon. Yorgen Fenech A prominent businessman arrested onboard his yacht as a person of interest in the Caruana Galizia investigation on 20 November 2019. One of the journalist's final investigations was a leak of data from his businesses. He has previously denied any wrongdoing. On 28 November his lawyers deposited a letter in court to Malta’s president formally asking for a pardon in return for information relating to the case. On 29 November the request was turned down. Keith Schembri and Konrad Mizzi The Maltese PM's chief of staff and the tourism minister resigned on 25 and 26 November 2019 respectively. Caruana Galizia reported that they had taken control of secretive Panama shell companies soon after entering office. They deny any wrongdoing. Schembri was arrested on 26 November and released on 28 November. Police said that after an 'intensive investigation' they no longer felt the need to hold him. Joseph Muscat Malta’s prime minister who served between 2013 to 2020. He was criticised by opposition politicians for allowing Schembri and Mizzi to stay in their posts. Having said on 29 November 2019 that he would stay in the job until the investigation into the murder was complete, on 1 December in a televised address he instead announced that he would stay on until a new leader of his ruling Labour party was elected in January. The prime minister expressed “deep regret” for Caruana Galizia’s murder and spoke of the need for a “fresh page”. Photograph: Darrin Zammit Lupi/X01097

Evidence later emerged that those companies were due to receive payments from a third shell company belonging to a well-known businessman. All those allegedly involved deny any allegations of impropriety.

The journalist’s revelations triggered a snap general election in 2017. Labour won by a landslide but the victory did not quell Malta’s political unrest. Five months later, Caruana Galizia died after her rental car exploded and spun into a field near her home in the village of Bidnija.

Tuesday’s ministerial departures followed a five-hour cabinet meeting, during which Muscat came under pressure from members of his party, including the deputy prime minister, to cut loose those in his circle associated with the Caruana Galizia story.

Muscat won the unanimous backing of his parliamentary party in a vote on Monday, but the prime minister is now battling for his political survival. He faces pressure not just from within his own party but from politicians and campaigners across Europe. His deputy, Chris Fearne, has described the damage from the scandal as “almost irreparable”.

Mizzi emerged from the prime minister’s office at Auberge de Castille, in Valletta, just after 3pm on Tuesday to announce his resignation.

Facebook Twitter Pinterest Demonstrators hold up an image of Daphne Caruana Galizia protest outside Malta’s parliament, in Valletta, on 26 November. Photograph: Domenic Aquilina/EPA

“In light of the extraordinary circumstances and the general sentiment in the country, I personally feel that the right thing to do at this moment in time is for me to step down,” he said. He denied the corruption allegations against him, saying he had “not done anything wrong from a criminal point of view”.

His departure came as police conducted a search of Schembri’s home in the north of the island. He had spent the morning being questioned at police headquarters. Schembri has headed Muscat’s office since the 2013 general election, which swept the Mediterranean nation’s Labour party to power after two decades in opposition. His lawyer did not respond to a request for comment.

Cardona was questioned by police in connection with Caruana Galizia’s murder on Saturday. In a statement, he said he was suspending himself “following a discussion with the prime minister”. “Dr Cardona declares that he has absolutely no connection with the case, but after police had asked for further clarifications, he feels duty bound to take this step in the national interest,” said the statement.

Muscat left Tuesday’s cabinet meeting without making a statement. The prime minister was bundled into his car by bodyguards as furious protesters shouted, among them Caruana Galizia’s sister Helene Asciak, who ran behind the vehicle before breaking down in tears.

European leaders are urging Muscat to step back and allow the judicial process to take its course away from the political arena. While the chief of police has made no public statements, the prime minister has been giving daily briefings in Maltese and English since a breakthrough in the inquiry last week.

Manfred Weber, the leader of the centre-right European People’s party in the European parliament, said Muscat faced “a lot of additional questions” following the resignation of his chief of staff. “The prime minister has to take over his political responsibility when it is about his cabinet,” Weber said. Describing the situation in Malta as worrying, he called on the Maltese authorities to clarify the situation “in the upcoming hours”.

Facebook Twitter Pinterest The late Maltese investigative journalist Daphne Caruana Galizia outside the Libyan embassy in Malta on 6 April 2011. Photograph: Darrin Zammit Lupi/Reuters

The European council’s special rapporteur on Malta, Pieter Omtzigt, who is monitoring the situation, published a letter in which he urged Muscat to distance himself from proceedings.

“The suspicions of Mr Muscat having a personal and political interest in the investigation are too strong for him to be involved with it,” Omtzigt wrote in a letter to Malta’s justice minister.

A coalition of press freedom organisations, including Reporters Without Borders and Transparency International, issued a joint statement, saying “the whole truth” must emerge.

“We are concerned that the prime minister, by placing himself at the centre of the investigation, raises the spectre of undue executive interference in the investigation. The financial interests of Muscat’s cabinet present the serious possibility of a conflict of interest for the prime minister with regard to the investigation.”

Asked on Tuesday morning whether he would now consider his own position, Muscat said: “I have always said I don’t intend seeking re-election. I don’t intend to serve more than two terms. My role right now is to make sure that we navigate through this turbulent time in the best possible manner. Once this chapter is closed with the arraignment of person or persons on this case I will make my consideration.”

Galizia’s family urged the authorities to act independently.