Secretary of State for Northern Ireland Brandon Lewis resigns

Mr Lewis told Boris Johnson the Government requires “honesty, integrity and mutual respect” and it is “now past the point of no return”,

His resignation early on Thursday came just hours after former Johnson ally Suella Braverman, the Attorney General, also publicly urged the Prime Minister to go.

Mr Johnson rejected calls to quit on Wednesday and dramatically sacked Cabinet rival Michael Gove.

He was later hit with the departure of a third Cabinet minister – Welsh Secretary Simon Hart.

Mr Johnson met ministers in No 10 on Wednesday, where he was told he has lost the confidence of the Conservative Party and should not continue in office – but refused to listen.

Mr Gove is thought to have told the Prime Minister on Wednesday morning that it is time for him to quit.

That was followed by a delegation of Cabinet ministers going to Downing Street to tell Mr Johnson he should stand down after losing the trust of his MPs.

They included Home Secretary Priti Patel, Business Secretary Kwasi Kwarteng, Transport Secretary Grant Shapps, Northern Ireland Secretary Mr Lewis and Welsh Secretary Mr Hart.

Allies including Culture Secretary Nadine Dorries and Brexit Opportunities Minister Jacob Rees-Mogg remained supportive of the Prime Minister.

Helen Whately, MP for Faversham and Mid Kent, also quit the Government early on Thursday.

Pensions minister and Hexam MP Guy Opperman has also resigned - he wrote on Twitter: “I resign with great regret, given there are serious ongoing issues that need addressing ranging from cost of living support, to legislation, & parliamentary debates.

“It should not take the resignation of 50 colleagues, but sadly the PM has left us no choice. He needs to resign.”

In his letter to the PM, he added: “I have given you ample opportunity to show real change. Sadly, recent events have shown clearly that the Government simply cannot function with you in charge. In good faith and for the good of the country, I must ask you to stand down. No one individual, however successful in the past, is bigger than the party, or this great country.”

George Freeman confirmed he had resigned from his post as science minister.

Science minister George Freeman said he no longer had confidence in Boris Johnson, saying “enough is enough”.

In a letter, he said: “It is with huge regret that I am writing to let you know that I no longer have confidence in your leadership of our country, Government or party, and am writing formally to Sir Graham Brady to register my support for a change of Conservative Party leadership.

“I do this with a very heavy heart. Our country is facing a series of crises and needs strong leadership, and needs ministers focused on delivering strong and effective government to deliver the priorities for which we won a massive majority only 30 months ago.

“I backed you then and since because of your commitment to make Brexit an inspiring moment of national renewal – of our economy, Parliamentary sovereignty and our place in the world – in the One Nation Conservative tradition on which you stood.”

The letter, which he signed “Minister for Science, Research and Innovation”, went on: “But I’m afraid the culmination of your lack of transparency and candour with Parliament (and willingness to ask your ministers to mislead Parliament), your removal of key pillars of the Ministerial code, your handling of your appointment of a deputy chief whip who it turns out you knew had a history of sexual abuse allegations, is too much. This is seriously damaging public trust and respect for government, democracy and the law, and this great party’s long tradition as the party of standards, character, conduct, integrity and duty to office and country before partisan self-interest.

“Your leadership, the chaos in No10, breakdown of Cabinet collective responsibility and collapse of public confidence in government represents a constitutional crisis. It is also now seriously undermining our authority in key negotiations on the world stage at a time of urgent international crises.”

Mr Freeman is understood to have cancelled a planned visit to Liverpool on Thursday linked to an announcement on funding for flu pandemic research.

And former Brexit negotiator Lord Frost has said that Boris Johnson cannot remain in Downing Street “because the business of government cannot continue”.

Lord Frost suggested he should not even be allowed to remain as a caretaker Prime Minister, if and when he steps down.

As the Prime Minister was hit by further resignations on Thursday morning, Lord Frost tweeted: “The Prime Minister cannot continue because the business of government cannot continue & because it is clear that he is not supported by his party in Parliament.

“I hoped he might have reflected overnight and come to realise that.

“If the PM insists on fighting this out then he will cause serious damage to the party and Government, and destroy his place in history.

“If he insists on waiting until another vote of MPs then the 1922 Exec should meet and facilitate one more quickly than planned.”

Urging Cabinet ministers to quit, he said: “He cannot now credibly be a caretaker Prime Minister while a leadership election is taking place. We have a Deputy PM who can straightforwardly fulfil that role and he should.”