AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home mLife Article
PDF (2.7 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Original Research | Open Access

Insertion sequence transposition activates antimycobacteriophage immunity through an lsr2‐silenced lipid metabolism gene island

Yakun Li,, Yuyun Wei, Xiao Guo, Xiaohui Li, Lining Lu, Lihua Hu, Zheng‐Guo He ( )
State Key Laboratory for Conservation and Utilization of Subtropical Agro‐Bioresources, Guangxi Research Center for Microbial and Enzyme Engineering Technology, College of Life Science and Technology, Guangxi University, Nanning, China

Editor: Hua Xiang, Institute of Microbiology, Chinese Academy of Sciences, China

Show Author Information

Abstract

Insertion sequences (ISs) exist widely in bacterial genomes, but their roles in the evolution of bacterial antiphage defense remain to be clarified. Here, we report that, under the pressure of phage infection, the IS1096 transposition of Mycobacterium smegmatis into the lsr2 gene can occur at high frequencies, which endows the mutant mycobacterium with a broad‐spectrum antiphage ability. Lsr2 functions as a negative regulator and directly silences expression of a gene island composed of 11 lipid metabolism‐related genes. The complete or partial loss of the gene island leads to a significant decrease of bacteriophage adsorption to the mycobacterium, thus defending against phage infection. Strikingly, a phage that has evolved mutations in two tail‐filament genes can re‐escape from the lsr2 inactivation‐triggered host defense. This study uncovered a new signaling pathway for activating antimycobacteriophage immunity by IS transposition and provided insight into the natural evolution of bacterial antiphage defense.

Keywords

bacteriophageantiphage defensegene islandinsertion sequencemycobacteria

References

1

Siguier P, Gourbeyre E, Chandler M. Bacterial insertion sequences: their genomic impact and diversity. FEMS Microbiol Rev. 2014;38:865–91.
Crossref Google Scholar
2

Siguier P, Filée J, Chandler M. Insertion sequences in prokaryotic genomes. Curr Opin Microbiol. 2006;9:526–31.
Crossref Google Scholar
3

Sheng Y, Wang H, Ou Y, Wu Y, Ding W, Tao M, et al. Insertion sequence transposition inactivates CRISPR‐Cas immunity. Nat Commun. 2023;14:4366.
Crossref Google Scholar
4

Abedon ST. Phage evolution and ecology. Adv Appl Microbiol. 2009;67:1–45.
Crossref Google Scholar
5

Twort FW. An investigation on the nature of ultra‐microscopic viruses. Lancet. 1915;186:1241–3.
Crossref Google Scholar
6

D'Herelle F. On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Herelle, presented by Mr. Roux. 1917. Res Microbiol. 2007;158:553–4.
Crossref Google Scholar
7

Chatterjee A, Johnson CN, Luong P, Hullahalli K, McBride SW, Schubert AM, et al. Bacteriophage resistance alters antibiotic‐mediated intestinal expansion of enterococci. Infect Immun. 2019;87:e00085–19.
Crossref Google Scholar
8

Olszak T, Latka A, Roszniowski B, Valvano MA, DrulisKawa Z. Phage life cycles behind bacterial biodiversity. Curr Med Chem. 2017;24:3987–4001.
Crossref Google Scholar
9

Davison S, Couture‐Tosi E, Candela T, Mock M, Fouet A. Identification of the Bacillus anthracis γ phage receptor. J Bacteriol. 2005;187:6742–9.
Crossref Google Scholar
10

McDonnell B, Hanemaaijer L, Bottacini F, Kelleher P, Lavelle K, Sadovskaya I, et al. A cell wall‐associated polysaccharide is required for bacteriophage adsorption to the Streptococcus thermophilus cell surface. Mol Microbiol. 2020;114:31–45.
Crossref Google Scholar
11

Gonzalez F, Helm RF, Broadway KM, Scharf BE. More than rotating flagella: lipopolysaccharide as a secondary receptor for flagellotropic phage 7‐7‐1. J Bacteriol. 2018;200:e00363–18.
Crossref Google Scholar
12

Raimondo LM, Lundh NP, Martinez RJ. Primary adsorption site of phage PBS1: the flagellum of Bacillus subtilis. J Virol. 1968;2:256–64.
Crossref Google Scholar
13

Labrie SJ, Samson JE, Moineau S. Bacteriophage resistance mechanisms. Nat Rev Microbiol. 2010;8:317–27.
Crossref Google Scholar
14

Xiong X, Wu G, Wei Y, Liu L, Zhang Y, Su R, et al. SspABCD‐SspE is a phosphorothioation‐sensing bacterial defence system with broad antiphage activities. Nat Microbiol. 2020;5:917–28.
Crossref Google Scholar
15

Ofir G, Melamed S, Sberro H, Mukamel Z, Silverman S, Yaakov G, et al. DISARM is a widespread bacterial defence system with broad antiphage activities. Nat Microbiol. 2018;3:90–8.
Crossref Google Scholar
16

Marraffini LA. CRISPR‐Cas immunity in prokaryotes. Nature. 2015;526:55–61.
Crossref Google Scholar
17

Garb J, Lopatina A, Bernheim A, Zaremba M, Siksnys V, Melamed S, et al. Multiple phage resistance systems inhibit infection via SIR2‐dependent NAD+ depletion. Nat Microbiol. 2022;7:1849–56.
Crossref Google Scholar
18

Tal N, Millman A, Stokar‐Avihail A, Fedorenko T, Leavitt A, Melamed S, et al. Bacteria deplete deoxynucleotides to defend against bacteriophage infection. Nat Microbiol. 2022;7:1200–9.
Crossref Google Scholar
19

Rousset F, Yirmiya E, Nesher S, Brandis A, Mehlman T, Itkin M, et al. A conserved family of immune effectors cleaves cellular ATP upon viral infection. Cell. 2023;186:3619–31.
Crossref Google Scholar
20

Bondy‐Denomy J, Pawluk A, Maxwell KL, Davidson AR. Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system. Nature. 2013;493:429–32.
Crossref Google Scholar
21

Hobbs SJ, Wein T, Lu A, Morehouse BR, Schnabel J, Leavitt A, et al. Phage anti‐CBASS and anti‐Pycsar nucleases subvert bacterial immunity. Nature. 2022;605:522–6.
Crossref Google Scholar
22

Huiting E, Cao X, Ren J, Athukoralage JS, Luo Z, Silas S, et al. Bacteriophages inhibit and evade cGAS‐like immune function in bacteria. Cell. 2023;186:864–76.
Crossref Google Scholar
23

Li W, He ZG. LtmA, a novel cyclic di‐GMP‐responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis. Nucleic Acids Res. 2012;40:11292–307.
Crossref Google Scholar
24

Bifani PJ, Mathema B, Liu Z, Moghazeh SL, Shopsin B, Tempalski B, et al. Identification of a W variant outbreak of Mycobacterium tuberculosis via population‐based molecular epidemiology. JAMA. 1999;282:2321–7.
Crossref Google Scholar
25

Antoine R, Gaudin C, Hartkoorn RC. Intragenic distribution of IS6110 in clinical Mycobacterium tuberculosis strains: bioinformatic evidence for gene disruption leading to underdiagnosed antibiotic resistance. Microbiol Spectr. 2021;9:e0001921.
Crossref Google Scholar
26

Cirillo JD, Barletta RG, Bloom BR, Jacobs Jr. WR. A novel transposon trap for mycobacteria: isolation and characterization of IS1096. J Bacteriol. 1991;173:7772–80.
Crossref Google Scholar
27

Wang XM, Galamba A, Warner DF, Soetaert K, Merkel JS, Kalai M, et al. IS1096‐mediated DNA rearrangements play a key role in genome evolution of Mycobacterium smegmatis. Tuberculosis. 2008;88:399–409.
Crossref Google Scholar
28

Wei W, Zhang S, Fleming J, Chen Y, Li Z, Fan S, et al. Mycobacterium tuberculosis type Ⅲ‐A CRISPR/Cas system crRNA and its maturation have atypical features. FASEB J. 2019;33:1496–509.
Crossref Google Scholar
29

Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998;393:537–44.
Crossref Google Scholar
30

Li X, Long X, Chen L, Guo X, Lu L, Hu L, et al. Mycobacterial phage TM4 requires a eukaryotic‐like Ser/Thr protein kinase to silence and escape antiphage immunity. Cell Host Microbe. 2023;31:1469–80.
Crossref Google Scholar
31

Gordon BRG, Imperial R, Wang L, Navarre WW, Liu J. Lsr2 of Mycobacterium represents a novel class of H‐NS‐like proteins. J Bacteriol. 2008;190:7052–9.
Crossref Google Scholar
32

Chen JM, Ren H, Shaw JE, Wang YJ, Li M, Leung AS, et al. Lsr2 of Mycobacterium tuberculosis is a DNA‐bridging protein. Nucleic Acids Res. 2008;36:2123–35.
Crossref Google Scholar
33

Summers EL, Meindl K, Usón I, Mitra AK, Radjainia M, Colangeli R, et al. The structure of the oligomerization domain of Lsr2 from Mycobacterium tuberculosis reveals a mechanism for chromosome organization and protection. PLoS One. 2012;7:e38542.
Crossref Google Scholar
34

Báez‐Ramírez E, Querales L, Aranaga CA, López G, Guerrero E, Kremer L, et al. Elimination of PknL and MSMEG_4242 in Mycobacterium smegmatis alters the character of the outer cell envelope and selects for mutations in Lsr2. Cell Surf. 2021;7:100060.
Crossref Google Scholar
35

Colangeli R, Haq A, Arcus VL, Summers E, Magliozzo RS, McBride A, et al. The multifunctional histone‐like protein Lsr2 protects mycobacteria against reactive oxygen intermediates. Proc Natl Acad Sci USA. 2009;106:4414–8.
Crossref Google Scholar
36

Bartek IL, Woolhiser LK, Baughn AD, Basaraba RJ, Jacobs Jr. WR, Lenaerts AJ, et al. Mycobacterium tuberculosis Lsr2 is a global transcriptional regulator required for adaptation to changing oxygen levels and virulence. mBio. 2014;5:e01106–14.
Crossref Google Scholar
37

Kołodziej M, Łebkowski T, Płociński P, Hołówka J, Paściak M, Wojtaś B, et al. Lsr2 and its novel paralogue mediate the adjustment of Mycobacterium smegmatis to unfavorable environmental conditions. mSphere. 2021;6:e00290–21.
Crossref Google Scholar
38

Dulberger CL, Guerrero‐Bustamante CA, Owen SV, Wilson S, Wuo MG, Garlena RA, et al. Mycobacterial nucleoid‐associated protein Lsr2 is required for productive mycobacteriophage infection. Nat Microbiol. 2023;8:695–710.
Crossref Google Scholar
39

Etienne G, Malaga W, Laval F, Lemassu A, Guilhot C, Daffé M. Identification of the polyketide synthase involved in the biosynthesis of the surface‐exposed lipooligosaccharides in mycobacteria. J Bacteriol. 2009;191:2613–21.
Crossref Google Scholar
40

Li Y, Li W, Xie Z, Xu H, He ZG. MpbR, an essential transcriptional factor for Mycobacterium tuberculosis survival in the host, modulates PIM biosynthesis and reduces innate immune responses. J Genet Genomics. 2019;46:575–89.
Crossref Google Scholar
41

Furuchi A, Tokunaga T. Nature of the receptor substance of Mycobacterium smegmatis for D4 bacteriophage adsorption. J Bacteriol. 1972;111:404–11.
Crossref Google Scholar
42

Chen J, Kriakov J, Singh A, Jacobs WR, Besra GS, Bhatt A. Defects in glycopeptidolipid biosynthesis confer phage I3 resistance in Mycobacterium smegmatis. Microbiology. 2009;155:4050–7.
Crossref Google Scholar
43

Wetzel KS, Illouz M, Abad L, Aull HG, Russell DA, Garlena RA, et al. Therapeutically useful mycobacteriophages BPs and Muddy require trehalose polyphleates. Nat Microbiol. 2023;8:1717–31.
Crossref Google Scholar
44

Imaeda T, Blas FS. Adsorption of mycobacteriophage on cell‐wall components. J Gen Virol. 1969;5:493–8.
Crossref Google Scholar
45
Tokunaga T, Sellers MI, Furuchi A. Phage receptor of Mycobacterium smegmatis. In: Juhasz E, Plummer G, editors. Host‐virus relationships in Mycobacterium, Nocardia and Actinomyces. Charles C Thomas; 1970. p. 119–33.
46

Sørensen MCH, van Alphen LB, Harboe A, Li J, Christensen BB, Szymanski CM, et al. Bacteriophage F336 recognizes the capsular phosphoramidate modification of Campylobacter jejuni NCTC11168. J Bacteriol. 2011;193:6742–9.
Crossref Google Scholar
47

Snapper SB, Melton RE, Mustafa S, Kieser T, Jacobs Jr. WR. Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol. 1990;4:1911–9.
Crossref Google Scholar
48

Yang M, Gao C, Cui T, An J, He ZG. A TetR‐like regulator broadly affects the expressions of diverse genes in Mycobacterium smegmatis. Nucleic Acids Res. 2012;40:1009–20.
Crossref Google Scholar
49

Li W, Li M, Hu L, Zhu J, Xie Z, Chen J, et al. HpoR, a novel c‐di‐GMP effective transcription factor, links the second messenger's regulatory function to the mycobacterial antioxidant defense. Nucleic Acids Res. 2018;46:3595–611.
Crossref Google Scholar
50

Rock JM, Hopkins FF, Chavez A, Diallo M, Chase MR, Gerrick ER, et al. Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform. Nat Microbiol. 2017;2:16274.
Crossref Google Scholar
51

Hu Q, Zhang J, Chen Y, Hu L, Li W, He ZG. Cyclic di‐GMP co‐activates the two‐component transcriptional regulator DevR in Mycobacterium smegmatis in response to oxidative stress. J Biol Chem. 2019;294:12729–42.
Crossref Google Scholar
52

Li X, Chen L, Liao J, Hui J, Li W, He ZG. A novel stress‐inducible CmtR‐ESX3‐Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress. J Biol Chem. 2020;295:17083–99.
Crossref Google Scholar
53
Mohammed HT, Mageeney CM, Ware VC. Identification of a new antiphage system in Mycobacterium phage butters. bioRxiv. 2023; https://doi.org/10.1101/2023.01.03.522681
Crossref
mLife
Volume 3 Issue 1,
March 2024
Pages 87-100
DOI: 10.1002/mlf2.12106
Cite this article:
Li Y, Wei Y, Guo X, et al. Insertion sequence transposition activates antimycobacteriophage immunity through an lsr2‐silenced lipid metabolism gene island. mLife, 2024, 3(1): 87-100. https://doi.org/10.1002/mlf2.12106

121

Views

16

Downloads

0

Crossref

0

Web of Science

0

Scopus

0

CSCD

Altmetrics
Received: 19 December 2023
Accepted: 26 January 2024
Published: 26 March 2024
© 2024 The Authors. mLife published by John Wiley & Sons Australia, Ltd on behalf of Institute of Microbiology, Chinese Academy of Sciences.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Return