000231697 001__ 231697
000231697 005__ 20181203024836.0
000231697 0247_ $$2doi$$a10.1128/Jb.00129-17
000231697 022__ $$a0021-9193
000231697 02470 $$2ISI$$a000408200400004
000231697 037__ $$aARTICLE
000231697 245__ $$aRv3852 (H-NS) of Mycobacterium tuberculosis Is Not Involved in Nucleoid Compaction and Virulence Regulation
000231697 260__ $$bAmer Soc Microbiology$$c2017$$aWashington
000231697 269__ $$a2017
000231697 300__ $$a12
000231697 336__ $$aJournal Articles
000231697 520__ $$aA handful of nucleoid-associated proteins (NAPs) regulate the vast majority of genes in a bacterial cell. H-NS, the histone-like nucleoid-structuring protein, is one of these NAPs and protects Escherichia coli from foreign gene expression. Though lacking any sequence similarity with E. coli H-NS, Rv3852 was annotated as the H-NS ortholog in Mycobacterium tuberculosis, as it resembles human histone H1. The role of Rv3852 was thoroughly investigated by immunoblotting, subcellular localization, construction of an unmarked rv3852 deletion in the M. tuberculosis genome, and subsequent analysis of the resulting Delta rv3852 strain. We found that Rv3852 was predominantly present in the logarithmic growth phase with a decrease in protein abundance in stationary phase. Furthermore, it was strongly associated with the cell membrane and not detected in the cytosolic fraction, nor was it secreted. The Delta rv3852 strain displayed no growth defect or morphological abnormalities. Quantitative measurement of nucleoid localization in the Delta rv3852 mutant strain compared to that in the parental H37Rv strain showed no difference in nucleoid position or spread. Infection of macrophages as well as severe combined immunodeficient (SCID) mice demonstrated that loss of Rv3852 had no detected influence on the virulence of M. tuberculosis. We thus conclude that M. tuberculosis Rv3852 is not involved in pathogenesis and is not a typical NAP. The existence of an as yet undiscovered Rv3852 ortholog cannot be excluded, although this role is likely played by the well-characterized Lsr2 protein. IMPORTANCE Mycobacterium tuberculosis is the causative agent of the lung infection tuberculosis, claiming more than 1.5 million lives each year. To understand the mechanisms of latent infection, where M. tuberculosis can stay dormant inside the human host, we require deeper knowledge of the basic biology and of the regulatory networks. In our work, we show that Rv3852, previously annotated as H-NS, is not a typical nucleoid-associated protein (NAP) as expected from its initial annotation. Rv3852 from M. tuberculosis has neither influence on nucleoid shape or compaction nor a role in virulence. Our findings reduce the repertoire of identified nucleoid-associated proteins in M. tuberculosis to four transcription regulators and underline the importance of genetic studies to assign a function to bacterial genes.
000231697 6531_ $$atuberculosis
000231697 6531_ $$aMycobacterium tuberculosis
000231697 6531_ $$aH-NS
000231697 6531_ $$aNAP
000231697 6531_ $$aglobal regulation
000231697 6531_ $$arv3852
000231697 700__ $$aOdermatt, Nina T.
000231697 700__ $$0244366$$g179660$$aSala, Claudia
000231697 700__ $$0246601$$g229809$$aBenjak, Andrej
000231697 700__ $$aKolly, Gaelle S.
000231697 700__ $$aVocat, Anthony
000231697 700__ $$aLupien, Andreanne
000231697 700__ $$0243892$$g177247$$aCole, Stewart T.
000231697 773__ $$j199$$tJournal Of Bacteriology$$k16$$qUNSP e00129-17
000231697 909C0 $$xU11742$$0252302$$pUPCOL
000231697 909CO $$pSV$$particle$$ooai:infoscience.tind.io:231697
000231697 917Z8 $$x282550
000231697 937__ $$aEPFL-ARTICLE-231697
000231697 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000231697 980__ $$aARTICLE