Researchers at Umeå University in Sweden, led by Professor Felipe Cava, have identified a new family of enzymes that creates a unique type of cross-linking between the building blocks of bacterial cell walls. This discovery could help develop new antibiotics against infectious diseases.
Bacterial cell walls form mesh-like structures, shielding cells from rupturing under high internal pressure and safeguarding against external threats. The cell wall is comprised of sugar and amino acid molecules interconnected by various types of cross-links. These cross-links play a crucial role in providing strength and stability to the cell wall, while also enabling bacteria to adapt to diverse environments and stressors.
In a groundbreaking study recently published in the esteemed journal Nature Communications, researchers from Umeå University and international institutions have unveiled a novel family of enzymes responsible for generating a unique cross-linkage between L-alanine and meso-diaminopimelic acid. These amino acids are integral components of the peptide chains constituting the cell wall of numerous bacterial species. Termed LD1,3-transpeptidase, this enzyme has been identified across various groups of alpha and beta proteobacteria, including opportunistic pathogens such as Burkholderia and Achromobacter.
The researchers utilized Gluconobacter oxydans, a model organism employed in vinegar production, to identify the novel LD1,3-transpeptidase enzyme and elucidate its three-dimensional structure. They have demonstrated that this enzyme possesses unique characteristics distinguishing it from other known enzymes involved in cell wall cross-linkage. These distinctive properties enable the enzyme to utilize various substrates and execute diverse reactions, critical for maintaining the cell wall's integrity. Specifically, their findings indicate that cells lacking these cross-links exhibit heightened sensitivity to β-lactam antibiotics, underscoring the potential of LD1,3-transpeptidases as promising targets for therapeutic interventions, particularly those aimed at enhancing antibiotic effectiveness.
The principal investigator of the study is Felipe Cava, Professor of Infection Biology at Umeå University and Director of the Umeå Hypoxic Research Facility. With extensive expertise in bacterial cell wall research and its implications in bacterial survival and disease progression, Professor Cava has spearheaded investigations into this field for a significant duration. The bacterial cell wall stands as one of the most remarkable structures, yet much remains to be uncovered about its diversity and dynamics. Through the identification and characterization of novel enzyme families like LD1,3-transpeptidase, we not only expand our understanding of bacterial biology but also discover fresh targets for developing antibiotics to combat infectious diseases."
Felipe Cava
The study was funded by, among others, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Kempe Foundations. Source:
Umeå UniversityJournal reference:
Espaillat, A., et al. (2024). A distinctive family of L,D-transpeptidases catalyzing L-Ala-mDAP crosslinks in Alpha- and Betaproteobacteria. Nature Communications. doi.org/10.1038/s41467-024-45620-5.
LOS ANGELES — Phillip Danault scored his second goal with 42 seconds to play, and the Los Angeles Kings blew a four-goal lead before rallying for a 6-5 victory over the Edmonton Oilers in the opener of the clubs’ fourth consecutive first-round playoff series Monday night.
The Kings led 5-3 in the final minutes before Zach Hyman and Connor McDavid tied it with an extra attacker. Los Angeles improbably responded, with Danault skating up the middle and chunking a fluttering shot home while a leaping Warren Foegele screened goalie Stuart Skinner.
Andrei Kuzmenko had a goal and two assists in his Stanley Cup playoff debut, and Adrian Kempe added another goal and two assists for the second-seeded Kings, who lost those last three series against Edmonton. Los Angeles became the fourth team in Stanley Cup playoffs history to win in regulation despite blowing a four-goal lead.
Los Angeles has home-ice advantage this spring for the first time in its tetralogy with Edmonton, and the Kings surged to a 4-0 lead late in the second period in the arena where they had the NHL’s best home record. That’s when the Oilers woke up and made it a memorable night: Leon Draisaitl, Mattias Janmark and Corey Perry scored before Hyman scored with 2:04 left and McDavid scored an exceptional tying goal with 1:28 remaining.
McDavid had a goal and three assists for the Oilers, who reached Game 7 of the Stanley Cup Final last season. Skinner stopped 24 shots.
Game 2 is Wednesday night in Los Angeles.
Until Edmonton’s late rally, Kuzmenko was the star. Los Angeles went 0 for 12 on the power play against Edmonton last spring, but the 29-year-old Russian — who has energized the Kings since arriving last month — scored during a man advantage just 2:49 in.
LOS ANGELES — Edmonton Oilers forward Jeff Skinner finally made his Stanley Cup playoff debut after 15 seasons and a league-record 1,078 regular-season games.
Skinner was in the lineup for Edmonton’s 6-5 loss in Game 1 of its first-round series against the Los Angeles Kings on Monday night, ending the longest wait for a postseason debut in NHL history.
Skinner, who turns 33 years old next month, has been an NHL regular since he was 18. He has racked up six 30-goal seasons and 699 total points while scoring 373 goals in a standout career.
But Skinner spent his first eight seasons of that career with the Carolina Hurricanes, at the time, a developing club that missed nine consecutive postseasons during the 2010s. From there, he spent the next six seasons with the woebegone Buffalo Sabres, whose current 14-season playoff drought is the league’s longest.
Skinner signed with Edmonton as a free agent last summer but struggled to nail down a consistent role in the Oilers’ lineup in the first half of the season. His game improved markedly in the second half, and he scored 16 goals this season while entering the playoffs as Edmonton’s third-line left wing.
Skinner’s teammates have been thrilled to end his drought this month. Connor McDavid presented Skinner with their player of the game award after the Oilers clinched their sixth straight playoff berth two weeks ago.
The veteran was active against the Kings, as his club mounted a furious rally only to lose in the final minute of regulation. Skinner had an assist and five hits across his 15 shifts. He finished the night with 11:12 time on the ice.
Harvard University is suing Donald Trump’s administration after it rejected a list of demands from the White House and had $2.2bn (£1.6bn) of government funding frozen.
The Ivy League institution, in Cambridge, Massachusetts, is accused of ideological bias and allowing antisemitism during campus protests last year against Israel’s war in Gaza.
The Trump administration, which began a review of $9bn (£6.7bn) in federal grants for Harvard in March, had demanded the university screen international students for those “hostile to the American values” and the end of all diversity, equality and inclusion programmes.
Image: Protesters earlier this month at Harvard called on the university to resist interference by the federal government. Pic: Reuters
Image: Students at a rally last week at Harvard against Donald Trump’s funding policies. Pic: AP
The university’s president Alan Garber has remained defiant and rejected those and other reforms, prompting the US President to question whether the university should lose its tax-exempt status.
Mr Trump accused the institution of pushing what he called “political, ideological, and terrorist inspired/supporting ‘Sickness?'” in a post on Truth Social.
Harvard has seen student-led protests in recent days calling on the institution to resist interference by the federal government.
Harvard’s lawsuit, filed in Boston, described the research funding freeze as “arbitrary and capricious” and violating its First Amendment rights.
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“The government has not – and cannot – identify any rational connection between antisemitism concerns and the medical, scientific, technological, and other research it has frozen that aims to save American lives, foster American success, preserve American security, and maintain America’s position as a global leader in innovation,” the court documents revealed.
Image: Harvard University has rejected a series of demands from the White House. File pic: AP
On Monday, White House spokesperson Harrison Fields issued a defiant response to the lawsuit: “The gravy train of federal assistance to institutions like Harvard, which enrich their grossly overpaid bureaucrats with tax dollars from struggling American families is coming to an end.
“Taxpayer funds are a privilege, and Harvard fails to meet the basic conditions required to access that privilege.”
The Trump administration has also paused some funding for universities including Columbia, Princeton, Cornell, Northwestern and Brown over the campus protests.
But protesters, including some Jewish groups, say their criticism of Israel’s military actions in Gaza is wrongly associated with antisemitism.
Mr Garber said the institution would continue to fight hate and fully comply with anti-discrimination laws.
Image: A small encampment in support of Palestinians at the Harvard campus in April 2024. Pic: Reuters
The American Council on Education, a non-profit organisation with more than 1,600 member colleges and universities, supported the legal action by Harvard.
“It has been clear for weeks that the administration’s actions violated due process and the rule of law. We applaud Harvard for taking this step.”