Streptococcus Pneumoniae Senses a Human-like Sialic Acid Profile Via the Response Regulator CiaR

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2016 Sep 6

PMID 27593514

Citations 30

Authors

Karina Hentrich

Jonas Lofling

Anuj Pathak

Victor Nizet

Ajit Varki

Birgitta Henriques-Normark

Affiliations

Soon will be listed here.

Abstract

Streptococcus pneumoniae is a human-adapted pathogen that encounters terminally sialylated glycoconjugates and free sialic acid (Sia) in the airways. Upon scavenging by the bacterial sialidase NanA, Sias serve as carbon sources for the bacteria. Unlike most animals in which cytidine-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) converts Sia N-acetylneuraminic acid (Neu5Ac) into N-glycolylneuraminic acid (Neu5Gc), humans have an inactive CMAH, causing an absence of Neu5Gc and excess Neu5Ac. We find that pneumococcal challenge in Cmah(-/-) mice leads to heightened bacterial loads, virulence, and NanA expression. In vitro, NanA is upregulated in response to Neu5Ac compared with Neu5Gc, a process controlled by the two-component response regulator CiaR and requiring Sia uptake by the transporter SatABC. Additionally, compared with Neu5Gc, Neu5Ac increases pneumococcal resistance to antimicrobial reactive oxygen species in a CiaR-dependent manner. Thus, S. pneumoniae senses and responds to Neu5Ac, leading to CiaR activation and increased virulence and potentially explaining the greater susceptibility in humans.

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References

Banda K, Gregg C, Chow R, Varki N, Varki A . Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J Biol Chem. 2012; 287(34):28852-64. PMC: 3436511. DOI: 10.1074/jbc.M112.364182. View

Pericone C, Park S, Imlay J, Weiser J . Factors contributing to hydrogen peroxide resistance in Streptococcus pneumoniae include pyruvate oxidase (SpxB) and avoidance of the toxic effects of the fenton reaction. J Bacteriol. 2003; 185(23):6815-25. PMC: 262707. DOI: 10.1128/JB.185.23.6815-6825.2003. View

Springer S, Diaz S, Gagneux P . Parallel evolution of a self-signal: humans and new world monkeys independently lost the cell surface sugar Neu5Gc. Immunogenetics. 2014; 66(11):671-4. PMC: 4198446. DOI: 10.1007/s00251-014-0795-0. View

Ibrahim Y, Kerr A, McCluskey J, Mitchell T . Role of HtrA in the virulence and competence of Streptococcus pneumoniae. Infect Immun. 2004; 72(6):3584-91. PMC: 415679. DOI: 10.1128/IAI.72.6.3584-3591.2004. View

Minami A, Ishibashi S, Ikeda K, Ishitsubo E, Hori T, Tokiwa H . Catalytic preference of Salmonella typhimurium LT2 sialidase for N-acetylneuraminic acid residues over N-glycolylneuraminic acid residues. FEBS Open Bio. 2013; 3:231-6. PMC: 3678298. DOI: 10.1016/j.fob.2013.05.002. View

Trappetti C, Kadioglu A, Carter M, Hayre J, Iannelli F, Pozzi G . Sialic acid: a preventable signal for pneumococcal biofilm formation, colonization, and invasion of the host. J Infect Dis. 2009; 199(10):1497-505. DOI: 10.1086/598483. View

Shaw L, Schauer R . Detection of CMP-N-acetylneuraminic acid hydroxylase activity in fractionated mouse liver. Biochem J. 1989; 263(2):355-63. PMC: 1133437. DOI: 10.1042/bj2630355. View

Vimr E, Kalivoda K, Deszo E, Steenbergen S . Diversity of microbial sialic acid metabolism. Microbiol Mol Biol Rev. 2004; 68(1):132-53. PMC: 362108. DOI: 10.1128/MMBR.68.1.132-153.2004. View

Paixao L, Caldas J, Kloosterman T, Kuipers O, Vinga S, Neves A . Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism. Front Microbiol. 2015; 6:1041. PMC: 4595796. DOI: 10.3389/fmicb.2015.01041. View

10.

Muchmore E, Diaz S, Varki A . A structural difference between the cell surfaces of humans and the great apes. Am J Phys Anthropol. 1998; 107(2):187-98. DOI: 10.1002/(SICI)1096-8644(199810)107:2<187::AID-AJPA5>3.0.CO;2-S. View

11.

Deng L, Song J, Gao X, Wang J, Yu H, Chen X . Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi. Cell. 2014; 159(6):1290-9. PMC: 4258231. DOI: 10.1016/j.cell.2014.10.057. View

12.

Makatsori E, Fermani K, Aletras A, Karamanos N, Tsegenidis T . Screening of N-acylneuraminic acids in serum and tissue specimens of mouse C57BI with Lewis' lung cancer by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1998; 712(1-2):23-9. DOI: 10.1016/s0378-4347(98)00150-9. View

13.

Pettigrew M, Fennie K, York M, Daniels J, Ghaffar F . Variation in the presence of neuraminidase genes among Streptococcus pneumoniae isolates with identical sequence types. Infect Immun. 2006; 74(6):3360-5. PMC: 1479257. DOI: 10.1128/IAI.01442-05. View

14.

Halfmann A, Kovacs M, Hakenbeck R, Bruckner R . Identification of the genes directly controlled by the response regulator CiaR in Streptococcus pneumoniae: five out of 15 promoters drive expression of small non-coding RNAs. Mol Microbiol. 2007; 66(1):110-26. DOI: 10.1111/j.1365-2958.2007.05900.x. View

15.

Mahajan V, Demissie E, Mattoo H, Viswanadham V, Varki A, Morris R . Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain. Cell Rep. 2016; 15(9):1901-9. PMC: 4892502. DOI: 10.1016/j.celrep.2016.04.080. View

16.

Sebert M, Palmer L, Rosenberg M, Weiser J . Microarray-based identification of htrA, a Streptococcus pneumoniae gene that is regulated by the CiaRH two-component system and contributes to nasopharyngeal colonization. Infect Immun. 2002; 70(8):4059-67. PMC: 128155. DOI: 10.1128/IAI.70.8.4059-4067.2002. View

17.

Marra A, Asundi J, Bartilson M, Lawson S, Fang F, Christine J . Differential fluorescence induction analysis of Streptococcus pneumoniae identifies genes involved in pathogenesis. Infect Immun. 2002; 70(3):1422-33. PMC: 127766. DOI: 10.1128/IAI.70.3.1422-1433.2002. View

18.

Gualdi L, Hayre J, Gerlini A, Bidossi A, Colomba L, Trappetti C . Regulation of neuraminidase expression in Streptococcus pneumoniae. BMC Microbiol. 2012; 12:200. PMC: 3509027. DOI: 10.1186/1471-2180-12-200. View

19.

Orihuela C, Gao G, Francis K, Yu J, Tuomanen E . Tissue-specific contributions of pneumococcal virulence factors to pathogenesis. J Infect Dis. 2004; 190(9):1661-9. DOI: 10.1086/424596. View

20.

Afzal M, Shafeeq S, Ahmed H, Kuipers O . Sialic acid-mediated gene expression in Streptococcus pneumoniae and role of NanR as a transcriptional activator of the nan gene cluster. Appl Environ Microbiol. 2015; 81(9):3121-31. PMC: 4393437. DOI: 10.1128/AEM.00499-15. View