Home > Archive>Volume 63, Issue 9, 2023 >3574-3590. DOI:10.13343/j.cnki.wsxb.20230010
PDF HTML XML Export Cite reminder
Acetyltransferase toxin SsGNAT affects adhesion of Streptococcus suis
Author:
  • Article
    • | |
  • Metrics
    • |
  • Reference [50]
    • |
  • Related [20]
    • | | |
  • Comments
    Abstract:

    [Objective] Streptococcus suis is a major zoonotic pathogen. This study aims to characterize the acetyltransferase toxin of the toxin-antitoxin system in Streptococcus suis and analyze the functions of the toxin, which may contribute to exploring the role of the toxin-antitoxin system in the infection of S. suis. [Methods] We first predicted the putative type Ⅱ toxin-antitoxin system in the genome of S. suis serotype 5 strain HN105. We further determined the activity and analyzed the phylogenetic relationship of the toxin-antitoxin system. Western blotting was employed to determine the expression of the toxin in S. suis. We constructed the toxin-deficient strain, antitoxin-deficient strain, and toxin-antitoxin-deficient strain with HN105 as the parental strain to explore the effects of the system on the adhesion, biofilm formation, anti-phagocytosis, and intracellular survival of S. suis. [Results] The Gcn5-related N-acetyltransferase (GNAT) toxin of the toxin-antitoxin system encoded by DF184_RS00980-DF184_RS00985 in the genome of the strain HN105 was predicted and identified, and the system was named SsMarR-SsGNAT based on the conserved domain. SsGNAT toxin exerted toxicity in the periplasmic space of Escherichia coli, and the antitoxin could neutralize the toxicity. SsGNAT toxin showed low amino acid sequence identity and distant genetic relationship with other acetyltransferase toxins. SsGNAT toxin was cleaved in S. suis, and the reduced expression of antitoxin upregulated the expression of SsGNAT toxin. SsGNAT toxin had no effect on the biofilm formation, anti-phagocytosis or intracellular survival of S. suis, while it affected the adhesion of S. suis to human laryngeal cancer epithelial cells (Hep-2) and human brain microvascular endothelial cells (HBMEC) cells. [Conclusion] We discovered and identified the novel type Ⅱ toxin-antitoxin system SsMarR-SsGNAT in S. suis. SsGNAT toxin exerted toxicity in the periplasmic space of E. coli, and its deletion promoted bacterial adhesion to cells. The findings provide a reference for further unraveling the pathogenic mechanism of S. suis.

    Reference
    [1] GOTTSCHALK M, XU JG, CALZAS C, SEGURA M. Streptococcus suis:a new emerging or an old neglected zoonotic pathogen?[J]. Future Microbiology, 2010, 5(3):371-391.
    [2] GOYETTE-DESJARDINS G, AUGER JP, XU JG, SEGURA M, GOTTSCHALK M. Streptococcus suis, an important pig pathogen and emerging zoonotic agent-an update on the worldwide distribution based on serotyping and sequence typing[J]. Emerging Microbes & Infections, 2014, 3(6):e45.
    [3] FENG YJ, ZHANG HM, WU ZW, WANG SH, CAO M, HU D, WANG CJ. Streptococcus suis infection:an emerging/reemerging challenge of bacterial infectious diseases?[J]. Virulence, 2014, 5(4):477-497.
    [4] TANG JQ, WANG CJ, FENG YJ, YANG WZ, SONG HD, CHEN ZH, YU HJ, PAN XZ, ZHOU XJ, WANG HR, WU B, WANG HL, ZHAO HM, LIN Y, YUE JH, WU ZQ, HE XW, GAO F, KHAN AH, WANG J, et al. Streptococcal toxic shock syndrome caused by Streptococcus suis serotype 2[J]. PLoS Medicine, 2006, 3(5):e151.
    [5] FENG YJ, ZHANG HM, MA Y, GAO GF. Uncovering newly emerging variants of Streptococcus suis, an important zoonotic agent[J]. Trends in Microbiology, 2010, 18(3):124-131.
    [6] OKURA M, OSAKI M, NOMOTO R, ARAI S, OSAWA R, SEKIZAKI T, TAKAMATSU D. Current taxonomical situation of Streptococcus suis[J]. Pathogens, 2016, 5(3):45.
    [7] PAN ZH, MA JL, DONG WY, SONG WC, WANG KC, LU CP, YAO HC. Novel variant serotype of Streptococcus suis isolated from piglets with meningitis[J]. Applied and Environmental Microbiology, 2015, 81(3):976-985.
    [8] QIU XT, BAI XM, LAN RT, ZHENG H, XU JG. Novel capsular polysaccharide loci and new diagnostic tools for high-throughput capsular gene typing in Streptococcus suis[J]. Applied and Environmental Microbiology, 2016, 82(24):7102-7112.
    [9] HUANG JH, LIU X, CHEN H, CHEN L, GAO XP, PAN ZH, WANG J, LU CP, YAO HC, WANG LP, WU ZF. Identification of six novel capsular polysaccharide loci (NCL) from Streptococcus suis multidrug resistant non-typeable strains and the pathogenic characteristic of strains carrying new NCLs[J]. Transboundary and Emerging Diseases, 2019, 66(2):995-1003.
    [10] ZHENG H, QIU XT, ROY D, SEGURA M, DU PC, XU JG, GOTTSCHALK M. Genotyping and investigating capsular polysaccharide synthesis gene loci of non-serotypeable Streptococcus suis isolated from diseased pigs in Canada[J]. Veterinary Research, 2017, 48(1):10.
    [11] ZHENG H, JI SB, LIU ZJ, LAN RT, HUANG Y, BAI XM, GOTTSCHALK M, XU JG. Eight novel capsular polysaccharide synthesis gene loci identified in nontypeable Streptococcus suis isolates[J]. Applied and Environmental Microbiology, 2015, 81(12):4111-4119.
    [12] YOSHIDA H, WADA T, TANIYAMA D, TAKAHASHI T. Draft genome sequence of clinical strain TANI1 of Streptococcus suis serotype 5 isolated from a bacteremia patient in Japan[J]. Genome Announcements, 2017, 5(18):e00260-17.
    [13] ZHU YC, ZHANG Y, MA JL, DONG WY, ZHONG XJ, PAN ZH, YAO HC. ICESsuHN105, a novel multiple antibiotic resistant ICE in Streptococcus suis serotype 5 strain HN105[J]. Frontiers in Microbiology, 2019, 10:274.
    [14] YAMAGUCHI Y, PARK JH, INOUYE M. Toxin-antitoxin systems in bacteria and archaea[J]. Annual Review of Genetics, 2011, 45:61-79.
    [15] OGURA T, HIRAGA S. Mini-F plasmid genes that couple host cell division to plasmid proliferation[J]. Proceedings of the National Academy of Sciences of the United States of America, 1983, 80(15):4784-4788.
    [16] LEPLAE R, GEERAERTS D, HALLEZ R, GUGLIELMINI J, DRÈZE P, van MELDEREN L. Diversity of bacterial type II toxin-antitoxin systems:a comprehensive search and functional analysis of novel families[J]. Nucleic Acids Research, 2011, 39(13):5513-5525.
    [17] GU QB, HE PJ, WANG D, MA JL, ZHONG XJ, ZHU YC, ZHANG Y, BAI QK, PAN ZH, YAO HC. An auto-regulating type II toxin-antitoxin system modulates drug resistance and virulence in Streptococcus suis[J]. Frontiers in Microbiology, 2021, 12:671706.
    [18] SALA A, BORDES P, GENEVAUX P. Multiple toxin-antitoxin systems in Mycobacterium tuberculosis[J]. Toxins, 2014, 6(3):1002-1020.
    [19] QI XY, BROTHERS KM, MA DZ, MANDELL JB, DONEGAN NP, CHEUNG AL, RICHARDSON AR, URISH KL. The Staphylococcus aureus toxin-antitoxin system YefM-YoeB is associated with antibiotic tolerance and extracellular dependent biofilm formation[J]. Journal of Bone and Joint Infection, 2021, 6(7):241-253.
    [20] JURĖNAS D, FRAIKIN N, GOORMAGHTIGH F, van MELDEREN L. Biology and evolution of bacterial toxin-antitoxin systems[J]. Nature Reviews Microbiology, 2022, 20(6):335-350.
    [21] FRAIKIN N, GOORMAGHTIGH F, van MELDEREN L. Type II toxin-antitoxin systems:evolution and revolutions[J]. Journal of Bacteriology, 2020, 202(7):e00763-19.
    [22] HARMS A, MAISONNEUVE E, GERDES K. Mechanisms of bacterial persistence during stress and antibiotic exposure[J]. Science, 2016, 354(6318):aaf4268.
    [23] TSILIBARIS V, MAENHAUT-MICHEL G, MINE N, van MELDEREN L. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome?[J]. Journal of Bacteriology, 2007, 189(17):6101-6108.
    [24] HU LI, LIMA BP, WOLFE AJ. Bacterial protein acetylation:the dawning of a new age[J]. Molecular Microbiology, 2010, 77(1):15-21.
    [25] VETTING MW, S de CARVALHO LP, YU M, HEGDE SS, MAGNET S, RODERICK SL, BLANCHARD JS. Structure and functions of the GNAT superfamily of acetyltransferases[J]. Archives of Biochemistry and Biophysics, 2005, 433(1):212-226.
    [26] QIAN HL, YU H, LI PF, ZHU E, YAO QQ, TAI C, DENG ZX, GERDES K, HE XY, GAN JH, OU HY. Toxin-antitoxin operon kacAT of Klebsiella pneumoniae is regulated by conditional cooperativity via a W-shaped KacA-KacT complex[J]. Nucleic Acids Research, 2019, 47(14):7690-7702.
    [27] CHEVERTON AM, GOLLAN B, PRZYDACZ M, WONG CT, MYLONA A, HARE SA, HELAINE S. A Salmonella toxin promotes persister formation through acetylation of tRNA[J]. Molecular Cell, 2016, 63(1):86-96.
    [28] JURĖNAS D, CHATTERJEE S, KONIJNENBERG A, SOBOTT F, DROOGMANS L, GARCIA-PINO A, van MELDEREN L. AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet[J]. Nature Chemical Biology, 2017, 13(6):640-646.
    [29] YU HJ, JING HQ, CHEN ZH, ZHENG H, ZHU XP, WANG H, WANG SW, LIU LG, ZU RQ, LUO LZ, XIANG NJ, LIU HL, LIU XC, SHU YL, LEE SS, CHUANG SK, WANG Y, XU JG, YANG WZ. Human Streptococcus suis outbreak, Sichuan, China[J]. Emerging Infectious Diseases, 2006, 12(6):914-920.
    [30] ZHU YC, DONG WY, MA JL, ZHANG Y, PAN ZH, YAO HC. Utilization of the ComRS system for the rapid markerless deletion of chromosomal genes in Streptococcus suis[J]. Future Microbiology, 2019, 14:207-222.
    [31] ZHONG XJ, MA JL, BAI QK, ZHU YC, ZHANG Y, GU QB, PAN ZH, LIU GJ, WU ZF, YAO HC. Identification of the RNA-binding domain-containing protein RbpA that acts as a global regulator of the pathogenicity of Streptococcus suis serotype 2[J]. Virulence, 2022, 13(1):1304-1314.
    [32] ZHONG XJ, ZHANG Y, ZHU YC, DONG WY, MA JL, PAN ZH, YAO HC. Identification of an autorepressing two-component signaling system that modulates virulence in Streptococcus suis serotype 2[J]. Infection and Immunity, 2019, 87(9):e00377-19.
    [33] JURĖNAS D, GARCIA-PINO A, van MELDEREN L. Novel toxins from type II toxin-antitoxin systems with acetyltransferase activity[J]. Plasmid, 2017, 93:30-35.
    [34] WILCOX B, OSTERMAN I, SEREBRYAKOVA M, LUKYANOV D, KOMAROVA E, GOLLAN B, MOROZOVA N, WOLF YI, MAKAROVA KS, HELAINE S, SERGIEV P, DUBILEY S, BORUKHOV S, SEVERINOV K. Escherichia coli ItaT is a type II toxin that inhibits translation by acetylating isoleucyl-tRNAIle[J]. Nucleic Acids Research, 2018, 46(15):7873-7885.
    [35] QIAN HL, YAO QQ, TAI C, DENG ZX, GAN JH, OU HY. Identification and characterization of acetyltransferase-type toxin-antitoxin locus in Klebsiella pneumoniae[J]. Molecular Microbiology, 2018, 108(4):336-349.
    [36] KOUKI A, PIETERS RJ, NILSSON UJ, LOIMARANTA V, FINNE J, HAATAJA S. Bacterial adhesion of Streptococcus suis to host cells and its inhibition by carbohydrate ligands[J]. Biology, 2013, 2(3):918-935.
    [37] FOSTER TJ, GEOGHEGAN JA, GANESH VK, HÖÖK M. Adhesion, invasion and evasion:the many functions of the surface proteins of Staphylococcus aureus[J]. Nature Reviews Microbiology, 2014, 12(1):49-62.
    [38] MARTINEZ-GIL M, GOH KGK, RACKAITYTE E, SAKAMOTO C, AUDRAIN B, MORIEL DG, TOTSIKA M, GHIGO JM, SCHEMBRI MA, BELOIN C. YeeJ is an inverse autotransporter from Escherichia coli that binds to peptidoglycan and promotes biofilm formation[J]. Scientific Reports, 2017, 7:11326.
    [39] XU B, ZHANG P, LI WY, LIU R, TANG JS, FAN HJ. hsdS, belonging to the type I restriction-modification system, contributes to the Streptococcus suis serotype 2 survival ability in phagocytes[J]. Frontiers in Microbiology, 2017, 8:1524.
    [40] YAO XY, CHEN T, SHEN XD, ZHAO Y, WANG M, RAO XC, YIN SP, WANG J, GONG YL, LU SG, LE S, TAN YL, TANG JQ, FUQUAN H, LI M. The chromosomal SezAT toxin-antitoxin system promotes the maintenance of the SsPI-1 pathogenicity island in epidemic Streptococcus suis[J]. Molecular Microbiology, 2015, 98(2):243-257.
    [41] ZHENG CK, XU JL, REN SJ, LI JQ, XIA MM, CHEN HC, BEI WC. Identification and characterization of the chromosomal yefM-yoeB toxin-antitoxin system of Streptococcus suis[J]. Scientific Reports, 2015, 5:13125.
    [42] YANG QE, WALSH TR. Toxin-antitoxin systems and their role in disseminating and maintaining antimicrobial resistance[J]. FEMS Microbiology Reviews, 2017, 41(3):343-353.
    [43] XU JL, ZHANG N, CAO MM, REN SJ, ZENG T, QIN ML, ZHAO XG, YUAN FY, CHEN HC, BEI WC. Identification of three type II toxin-antitoxin systems in Streptococcus suis serotype 2[J]. Toxins, 2018, 10(11):467.
    [44] WEN W, LIU BH, XUE L, ZHU ZL, NIU LW, SUN BL. Autoregulation and virulence control by the toxin-antitoxin system SavRS in Staphylococcus aureus[J]. Infection and Immunity, 2018, 86(5):e00032-18.
    [45] MUTSCHLER H, GEBHARDT M, SHOEMAN RL, MEINHART A. A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis[J]. PLoS Biology, 2011, 9(3):e1001033.
    [46] KLINE KA, FÄLKER S, DAHLBERG S, NORMARK S, HENRIQUES-NORMARK B. Bacterial adhesins in host-microbe interactions[J]. Cell Host Microbe, 2009, 5(6):580-592.
    [47] PAN ZH, HE PJ, ZHANG Y, GU QB, CHEN SS, YU Y, SHAO J, WANG KC, WU ZF, YAO HC, MA JL. SssP1, a Fimbria-like component of Streptococcus suis, binds to the vimentin of host cells and contributes to bacterial meningitis[J]. PLoS Pathogens, 2022, 18(7):e1010710.
    [48] BURIAN M, RAUTENBERG M, KOHLER T, FRITZ M, KRISMER B, UNGER C, HOFFMANN WH, PESCHEL A, WOLZ C, GOERKE C. Temporal expression of adhesion factors and activity of global regulators during establishment of Staphylococcus aureus nasal colonization[J]. The Journal of Infectious Diseases, 2010, 201(9):1414-1421.
    [49] KREIKEMEYER B, OEHMCKE S, NAKATA M, HOFFROGGE R, PODBIELSKI A. Streptococcus pyogenes fibronectin-binding protein F2:expression profile, binding characteristics, and impact on eukaryotic cell interactions[J]. The Journal of Biological Chemistry, 2004, 279(16):15850-15859.
    [50] BATCHELOR M, PRASANNAN S, DANIELL S, REECE S, CONNERTON I, BLOOMBERG G, DOUGAN G, FRANKEL G, MATTHEWS S. Structural basis for recognition of the translocated intimin receptor (Tir) by intimin from enteropathogenic Escherichia coli[J]. The EMBO Journal, 2000, 19(11):2452-2464.
    Cited by
    Comments
    Comments
    分享到微博
    Submit
Get Citation

ZHU Xiayu, GU Qibing, YANG Xuemei, YAO Huochun, PAN Zihao. Acetyltransferase toxin SsGNAT affects adhesion of Streptococcus suis. [J]. Acta Microbiologica Sinica, 2023, 63(9): 3574-3590

Copy
Share
Article Metrics
  • Abstract:271
  • PDF: 724
  • HTML: 569
  • Cited by: 0
History
  • Received:January 04,2023
  • Revised:April 13,2023
  • Online: August 29,2023
  • Published: September 04,2023
Article QR Code
  • WeChat ID
  • Mobile Terminal

Acta Microbiologica Sinica ® 2025 All Rights Reserved