Two codependent routes lead to high-level MRSA

被引：12

作者：

Adedeji-Olulana, Abimbola Feyisara ^{[1
]}

Wacnik, Katarzyna ^{[2
,3
]}

Lafage, Lucia ^{[2
,3
]}

Pasquina-Lemonche, Laia ^{[1
,3
]}

Tinajero-Trejo, Mariana ^{[2
,3
]}

Sutton, Joshua A. F. ^{[2
,3
]}

Bilyk, Bohdan ^{[2
,3
]}

Irving, Sophie E. ^{[2
,3
]}

Ross, Callum J. Portman ^{[2
,3
]}

Meacock, Oliver J. ^{[1
]}

Randerson, Sam A. ^{[1
]}

Beattie, Ewan ^{[1
]}

Owen, David S. ^{[2
,5
]}

Florence, James ^{[2
,3
,6
]}

Durham, William M. ^{[1
]}

Hornby, David P. ^{[2
,3
]}

Corrigan, Rebecca M. ^{[2
,3
,4
]}

Green, Jeffrey ^{[2
,3
]}

Hobbs, Jamie K. ^{[1
]}

Foster, Simon J. ^{[2
,3
]}

机构：

[1] Univ Sheffield, Sch Math & Phys Sci, Sheffield, England

[2] Univ Sheffield, Sch Biosci, Sheffield, England

[3] Univ Sheffield, Florey Inst, Sheffield, England

[4] Univ Coll Dublin, Sch Med, Dublin, Ireland

[5] Sheffield Hallam Univ, Dept Biosci & Chem, Sheffield, England

[6] Entropix Ltd, Runcorn, England

来源：

SCIENCE | 2024年 / 386卷 / 6721期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

BETA-LACTAM-RESISTANCE; CELL-WALL; METHICILLIN RESISTANCE; VIRULENCE; STRAINS; SUSCEPTIBILITY; TRANSMISSION; EXPRESSION; EVOLUTION; DIVISION;

D O I：

10.1126/science.adn1369

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Methicillin-resistant Staphylococcus aureus (MRSA), in which acquisition of mecA [which encodes the cell wall peptidoglycan biosynthesis component penicillin-binding protein 2a (PBP2a)] confers resistance to beta-lactam antibiotics, is of major clinical concern. We show that, in the presence of antibiotics, MRSA adopts an alternative mode of cell division and shows an altered peptidoglycan architecture at the division septum. PBP2a can replace the transpeptidase activity of the endogenous and essential PBP2 but not that of PBP1, which is responsible for the distinctive native septal peptidoglycan architecture. Successful division without PBP1 activity requires the alternative division mode and is enabled by several possible chromosomal potentiator (pot) mutations. MRSA resensitizing agents differentially interfere with the two codependent mechanisms required for high-level antibiotic resistance, which provides opportunities for new interventions.

引用

页码：573 / 580

页数：7

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