염진기 (서울대학교 의과대학, Yale School of Medicine, Duke-NUS Medical School) | 한빛사논문 > 한빛사

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서울대학교 의과대학, Yale School of Medicine, Duke-NUS Medical School

Proc. Natl. Acad. Sci. USA, First published August 4, 2020 | https://doi.org/10.1073/pnas.2006116117 Small proteins regulate Salmonella survival inside macrophages by controlling degradation of a magnesium transporter

Jinki Yeom^a,b,c, Yi Shao^a, and Eduardo A. Groisman^a,d,1

^aDepartment of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06536; ^bProgram in Emerging Infectious Diseases, Duke-NUS Medical School, 169857 Singapore, Republic of Singapore; ^cDepartment of Microbiology and Immunology, College of Medicine, Seoul National University, 03080 Seoul, Korea; and ^dYale Microbial Sciences Institute, Yale University, West Haven, CT 06516

¹To whom correspondence may be addressed.

Abstract

All cells require Mg2+ to replicate and proliferate. The macrophage protein Slc11a1 is proposed to protect mice from invading microbes by causing Mg2+ starvation in host tissues. However, the Mg2+ transporter MgtB enables the facultative intracellular pathogen Salmonella enterica serovar Typhimurium to cause disease in mice harboring a functional Slc11a1 protein. Here, we report that, unexpectedly, the Salmonella small protein MgtR promotes MgtB degradation by the protease FtsH, which raises the question: How does Salmonella preserve MgtB to promote survival inside macrophages? We establish that the Salmonella small protein MgtU prevents MgtB proteolysis, even when MgtR is absent. Like MgtB, MgtU is necessary for survival in Slc11a1+/+ macrophages, resistance to oxidative stress, and growth under Mg2+ limitation conditions. The Salmonella Mg2+ transporter MgtA is not protected by MgtU despite sharing 50% amino acid identity with MgtB and being degraded in an MgtR- and FtsH-dependent manner. Surprisingly, the mgtB, mgtR, and mgtU genes are part of the same transcript, providing a singular example of transcript-specifying proteins that promote and hinder degradation of the same target. Our findings demonstrate that small proteins can confer pathogen survival inside macrophages by altering the abundance of related transporters, thereby furthering homeostasis.

FtsH, MgtB, MgtR, MgtU, proteolysis

논문정보

형식Research article
게재일2020년 08월 (BRIC 등록일 2020-08-06)
연구진국내+국외 연구진
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