Single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities

被引：1

作者：

Hira, Jonathan ^{[1
,2
]}

Singh, Bhupender ^{[1
,2
]}

Halder, Tirthankar ^{[1
,2
]}

Mahmutovic, Anel ^{[3
]}

Ajayi, Clement ^{[1
,2
]}

Sekh, Arif Ahmed ^{[4
]}

Hegstad, Kristin ^{[1
,2
,5
]}

Johannessen, Mona ^{[1
,2
]}

Lentz, Christian S. ^{[1
,2
]}

机构：

[1] UiT Arctic Univ Norway, Ctr New Antibacterial Strategies CANS, Tromso, Norway

[2] UiT Arctic Univ Norway, Dept Med Biol, Res Grp Host Microbe Interact, Tromso, Norway

[3] AstraZeneca, Biopharmaceut RD AstraZeneca, Early Biometr & Stat Innovat Data Sci & AI, Molndal, Sweden

[4] XIM Univ, Bhubaneswar, India

[5] Univ Hosp North Norway, Dept Microbiol & Infect Control, Norwegian Natl Advisory Unit Detect Antimicrobial, Tromso, Norway

来源：

COMMUNICATIONS BIOLOGY | 2024年 / 7卷 / 01期

关键词：

VANCOMYCIN RESISTANCE; PERSISTER CELLS; ESCHERICHIA-COLI; STRAINS; WALL; HETEROGENEITY; USA300; GROWTH;

D O I：

10.1038/s42003-024-06894-z

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Isogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversibility of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present <acute accent>Cellular Phenotypic Profiling and backTracing (CPPT)<acute accent>, a fluorescence-activated cell sorting platform that uses fluorescent probes to visualize and quantify cellular traits and connects this phenotypic profile with a cell<acute accent>s experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis. By applying CPPT on Staphylococcus aureus we phenotypically characterized dormant cells, exposed bimodal growth patterns in colony-derived cells and revealed different culturability of single cells on solid compared to liquid media. We demonstrate that a fluorescent vancomycin conjugate marks cellular subpopulations of vancomycin-intermediate S. aureus with increased likelihood to survive antibiotic exposure, showcasing the value of CPPT for discovery of clinically relevant biomarkers.

引用

页数：15

共 80 条

[1] Self-destructive cooperation mediated by phenotypic noise [J].