Human MAIT cell cytolytic effector proteins synergize to overcome carbapenem resistance in Escherichia coli

• DOI: 10.1371/journal.pbio.3000644
• Publication Date: 2020-06-08T17:33:48Z
• Authors: Caroline Boulouis; Wan Rong Sia; Muhammad Yaaseen ...; Jocelyn Qi Min Teo; Yi Tian Png; Thanh Kha Phan; Jeffrey Y. W. Mak; David P. Fairlie; Ivan K. H. Poon; Tse Hsien Koh; Peter Bergman; Chwee Ming Lim; Lin-Fa Wang; Andrea Lay Hoon Kwa; Johan K. Sandberg; Edwin Leeansyah
• Keywords: Granulysin; Granzyme

Mucosa-associated invariant T (MAIT) cells are abundant antimicrobial in humans and recognize antigens derived from the microbial riboflavin biosynthetic pathway presented by MHC-Ib-related protein (MR1). However, mechanisms responsible for MAIT cell activity not fully understood, efficacy of these against antibiotic resistant bacteria has been explored. Here, we show that mediate MR1-restricted Escherichia coli clinical strains a manner dependent on cytolytic proteins but independent production pro-inflammatory cytokines or induction apoptosis infected cells. The combined action pore-forming granulysin serine protease granzyme B released response to receptor (TCR)-mediated recognition MR1-presented antigen is essential control both cell-associated free-living, extracellular forms E. coli. Furthermore, cell-mediated bacterial extends multidrug-resistant primary isolates additionally carbapenems, class last resort antibiotics. Notably, high levels secretomes directly damage increasing their permeability, rendering initially susceptible bactericidal carbapenems. These findings define role effector indicate synergize restore carbapenem overcome resistance