针对一种保守表面多糖的抗体能够对产β-1,6-聚-<i>N</i>-乙酰葡萄糖胺（PNAG）的多种微生物病原体具有保护作用

Xi Lu; Guoqing Li; Jing Pang; Xinyi Yang; Colette Cywes-Bentley; Xuefu You; Gerald B. Pier

doi:10.1016/j.eng.2023.09.012

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工程（英文） ›› 2024, Vol. 38 ›› Issue (7) : 69-76. DOI: 10.1016/j.eng.2023.09.012

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针对一种保守表面多糖的抗体能够对产β-1,6-聚-N-乙酰葡萄糖胺（PNAG）的多种微生物病原体具有保护作用

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Antibodies Targeting a Conserved Surface Polysaccharide Are Protective Against a Wide Range of Microbial Pathogens Producing β-1-6-Linked Poly-N-Acetylglucosamine (PNAG)

Xi Lu ^a^,^# ,
Guoqing Li ^a^,^# ,
Jing Pang ^a^,^# ,
Xinyi Yang ^a ,
Colette Cywes-Bentley ^b ,
Xuefu You ^a ,
Gerald B. Pier ^b^,^*

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Abstract

Theβ-1-6 -linked poly- N -acetylglucosamine (PNAG) polymer is a conserved surface polysaccharide produced by many bacteria, fungi, and protozoan (and even filarial) parasites. This wide-ranging expression makes PNAG an attractive target for vaccine development, as it potentially encompasses a broad range of microorganisms. Significant progress has been made in discovering important properties of the biology of PNAG expression in recent years. The molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many bacteria. In addition, the physiological function of PNAG has been further elucidated. PNAG-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical research. Furthermore, clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals, and the results are promising. Although it is not destined to be a smooth road, we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

Keywords

Poly- N-acetylglucosamine / Conjugate vaccine / Monoclonal antibody

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Xi Lu, Guoqing Li, Jing Pang. 靶向保守表面多糖的抗体对产生多聚β-1-6-N-乙酰氨基葡萄糖胺的各种微生物病原体具有保护作用. Engineering. 2024, 38(7): 69-76 https://doi.org/10.1016/j.eng.2023.09.012

参考文献

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[1]	C. Cywes-Bentley, D. Skurnik, T. Zaidi, D. Roux, R.B. Deoliveira, W.S. Garrett, et al. Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens. Proc Natl Acad Sci USA, 110 (24) (2013), pp. E2209-E2218
[2]	A.T. Kocer, B. Inan, S.K. Usul, D. Özçimen, M.T. Yilmaz, I. Işıldak. EPSs from microalgae: production, characterization, optimization and techno-economic assessment. Braz J Microbiol, 52 (4) (2021), pp. 1779-1790
[3]	A.K. Abdalla, M.M. Ayyash, A.N. Olaimat, T.M. Osaili, A.A. Al-Nabulsi, N.P. Shah, et al. EPSs as antimicrobial agents: mechanism and spectrum of activity. Front Microbiol, 12 (2021), Article 664395
[4]	L. Tounsi, F. Hentati, H.B. Hlima, M. Barkallah, S. Smaoui, I. Fendri, et al. Microalgae as feedstock for bioactive polysaccharides. Int J Biol Macromol, 221 (2022), pp. 1238-1250
[5]	I. Jawad, H.B. Tawseen, M. Irfan, W. Ahmad, M. Hassan, F. Sattar, et al. Dietary supplementation of microbial dextran and inulin exerts hypocholesterolemic effects and modulates gut microbiota in BALB/c mice models. Int J Mol Sci, 24 (6) (2023), p. 5314
[6]	M.M. Nadzir, R.W. Nurhayati, F.N. Idris, M.H. Nguyen. Biomedical applications of bacterial EPSs: a review. Polymers, 13 (4) (2021), p. 530
[7]	G.B. Whitfield, L.S. Marmont, P.L. Howell. Enzymatic modifications of EPSs enhance bacterial persistence. Front Microbiol, 6 (2015), p. 471
[8]	D. Skurnik, C. Cywes-Bentley, G.B. Pier. The exceptionally broad-based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG. Expert Rev Vaccines, 15 (8) (2016), pp. 1041-1053
[9]	P. Yoong, C. Cywes-Bentley, G.B. Pier. Poly-N-acetylglucosamine expression by wild-type Yersinia pestis is maximal at mammalian, not flea, temperatures. mBio, 3 (4) (2012), pp. e00217-12
[10]	D. Skurnik, M.R. Jr, Davis Jr, D. Benedetti, K.L. Moravec, C. Cywes-Bentley, D. Roux, et al. Targeting pan-resistant bacteria with antibodies to a broadly conserved surface polysaccharide expressed during infection. J Infect Dis, 205 (11) (2012), pp. 1709-1718
[11]	C. Cywes-Bentley, J.N. Rocha, A.I. Bordin, M. Vinacur, S. Rehman, T.S. Zaidi, et al. Antibody to poly-N-acetyl glucosamine provides protection against intracellular pathogens: mechanism of action and validation in horse foals challenged with Rhodococcus equi. PLoS Pathog, 14 (7) (2018), Article e1007160
[12]	M. Shanmugam, A.O. Oyeniyi, C. Parthiban, S.K. Gujjarlapudi, G.B. Pier, N. Ramasubbu. Role of de-N-acetylase PgaB from Aggregatibacter actinomycetemcomitans in exopolysaccharide export in biofilm mode of growth. Mol Oral Microbiol, 32 (6) (2017), pp. 500-510
[13]	N.S. Taus, C. Cywes-Bentley, W.C. Johnson, G.B. Pier, L.M. Fry, M.R. Mousel, et al. Immunization against a conserved surface polysaccharide stimulates bovine antibodies with opsonic killing activity but does not protect against Babesia bovis challenge. Pathogens, 10 (12) (2021), p. 1598
[14]	Y. Ramos, J. Rocha, A.L. Hael, J. van Gestel, H. Vlamakis, C. Cywes-Bentley, et al. PolyGlcNAc-containing exopolymers enable surface penetration by non-motile Enterococcus faecalis. PLoS Pathog, 15 (2) (2019), Article e1007571
[15]	D. Van Dissel, J. Willemse, B. Zacchetti, D. Claessen, G.B. Pier, G.P. van Wezel. Production of poly-β-1,6-N-acetylglucosamine by MatAB is required for hyphal aggregation and hydrophilic surface adhesion by Streptomyces. Microb Cell, 5 (6) (2018), pp. 269-279
[16]	T.C. Stevenson, C. Cywes-Bentley, T.D. Moeller, K.B. Weyant, D. Putnam, Y.F. Chang, et al. Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies. Proc Natl Acad Sci USA, 115 (14) (2018), pp. E3106-E3115
[17]	G. Zhao, T.S. Zaidi, C. Bozkurt-Guzel, T.H. Zaidi, J.A. Lederer, G.P. Priebe, et al. Efficacy of antibody to PNAG against keratitis caused by fungal pathogens. Invest Ophthalmol Visual Sci, 57 (15) (2016), pp. 6797-6804
[18]	D. Roux, C. Cywes-Bentley, Y.F. Zhang, S. Pons, M. Konkol, D.B. Kearns, et al. Identification of poly-N-acetylglucosamine as a major polysaccharide component of the Bacillus subtilis biofilm matrix. J Biol Chem, 290 (31) (2015), pp. 19261-19272
[19]	D.H. Kwan, S.G. Withers. Periplasmic de-acylase helps bacteria don their biofilm coat. Proc Natl Acad Sci USA, 111 (30) (2014), pp. 10904-10905
[20]	D.J. Little, G. Li, C. Ing, B.R. DiFrancesco, N.C. Bamford, H. Robinson, et al. Modification and periplasmic translocation of the biofilm exopolysaccharide poly-β-1,6-N-acetyl-D-glucosamine. Proc Natl Acad Sci USA, 111 (30) (2014), pp. 11013-11018
[21]	S. Steiner, C. Lori, A. Boehm, U. Jenal. Allosteric activation of exopolysaccharide synthesis through cyclic di-GMP-stimulated protein-protein interaction. EMBO J, 32 (3) (2013), pp. 354-368
[22]	D.J. Little, R. Pfoh, F. Le Mauff, N.C. Bamford, C. Notte, P. Baker, et al. PgaB orthologues contain a glycoside hydrolase domain that cleaves deacetylated poly-β(1,6)-N-acetylglucosamine and can disrupt bacterial biofilms. PLoS Pathog, 14 (4) (2018), Article e1006998
[23]	E. Balducci, F. Papi, E. Capialbi, L. Del Bino. Polysaccharides’ structures and functions in biofilm architecture of antimicrobial-resistant (AMR) pathogens. Int J Mol Sci, 24 (4) (2023), p. 4030
[24]	I.R. De los Mozos, M. Vergara-Irigaray, V. Segura, M. Villanueva, N. Bitarte, M. Saramago, et al. Base pairing interaction between 5′- and 3′-UTRs controls icaR mRNA translation in Staphylococcus aureus. PLoS Genet, 9 (12) (2013), Article e1004001
[25]	M. Echeverz, B. Garcia, A. Sabalza, J. Valle, T. Gabaldon, C. Solano, et al. Lack of the PGA exopolysaccharide in Salmonella as an adaptive trait for survival in the host. PLoS Genet, 13 (5) (2017), Article e1006816
[26]	H.T.T. Nguyen, T.H. Nguyen, M. Otto. The staphylococcal exopolysaccharide PIA—biosynthesis and role in biofilm formation, colonization, and infection. Comput Struct Biotechnol J, 18 (2020), pp. 3324-3334
[27]	A.R. Fullen, J.L. Gutierrez-Ferman, K.S. Yount, C.F. Love, H.G. Choi, M.A. Vargas, et al. BPS polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen. PLoS Pathog, 18 (8) (2022), Article e1010764
[28]	C.R. Arciola, L. Baldassarri, L. Montanaro. In catheter infections by Staphylococcus epidermidis the intercellular adhesion (ica) locus is a molecular marker of the virulent slime-producing strains. J Biomed Mater Res, 59 (3) (2002), pp. 557-562
[29]	T. Maira-Litrán, A. Kropec, D.A. Goldmann, G.B. Pier.Comparative opsonic and protective activities of Staphylococcus aureus conjugate vaccines containing native or deacetylated staphylococcal poly-N-acetyl-β-(1-6) -glucosamine. Infect Immun, 73 (10) (2005), pp. 6752-6762
[30]	S. Pons, E. Frapy, Y. Sereme, C. Gaultier, F. Lebreton, A. Kropec, et al. A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates. EBioMedicine, 88 (2023), Article 104439
[31]	C. Pozzi, K. Wilk, J.C. Lee, M. Gening, N. Nifantiev, G.B. Pier. Opsonic and protective properties of antibodies raised to conjugate vaccines targeting six Staphylococcus aureus antigens. PLoS One, 7 (10) (2012), Article e46648
[32]	D. Skurnik, M. Merighi, M. Grout, M. Gadjeva, T. Maira-Litran, M. Ericsson, et al. Animal and human antibodies to distinct Staphylococcus aureus antigens mutually neutralize opsonic killing and protection in mice. J Clin Invest, 120 (9) (2010), pp. 3220-3233
[33]	M.L. Gening, T. Maira-Litrán, A. Kropec, D. Skurnik, M. Grout, Y.E. Tsvetkov, et al. Synthetic β-(1→6)-linked N-acetylated and nonacetylated oligoglucosamines used to produce conjugate vaccines for bacterial pathogens. Infect Immun, 78 (2) (2010), pp. 764-772
[34]	T. Zaidi, T. Zaidi, P. Yoong, G.B. Pier. Staphylococcus aureus corneal infections: effect of the Panton-Valentine leukocidin (PVL) and antibody to PVL on virulence and pathology. Invest Ophthalmol Visual Sci, 54 (7) (2013), pp. 4430-4438
[35]	T.S. Zaidi, T. Zaidi, G.B. Pier. Antibodies to conserved surface polysaccharides protect mice against bacterial conjunctivitis. Invest Ophthalmol Visual Sci, 59 (6) (2018), pp. 2512-2519
[36]	T. Maira-Litrán, L.V. Bentancor, C. Bozkurt-Guzel, J.M. O’Malley, C. Cywes-Bentley, G.B. Pier. Synthesis and evaluation of a conjugate vaccine composed of Staphylococcus aureus poly-N-acetyl-glucosamine and clumping factor A.PLoS One, 7 (9) (2012), p. e43813
[37]	N.H. Søe, N.V. Jensen, A.L. Jensen, J. Koch, S.S. Poulsen, G.B. Pier, et al. Active and passive immunization against Staphylococcus aureus periprosthetic osteomyelitis in rats. In Vivo, 31 (1) (2017), pp. 45-50
[38]	S.K. Kahn, C. Cywes-Bentley, G.P. Blodgett, N.M. Canaday, C.E. Turner-Garcia, M. Vinacur, et al. Antibody activities in hyperimmune plasma against the Rhodococcus equi virulence-associated protein A or poly-N-acetyl glucosamine are associated with protection of foals against rhodococcal pneumonia. PLoS One, 16 (8) (2021), Article e0250133
[39]	S.K. Kahn, C. Cywes-Bentley, G.P. Blodgett, N.M. Canaday, C.E. Turner-Garcia, P. Flores-Ahlschwede, et al. Randomized, controlled trial comparing Rhodococcus equi and poly-N-acetyl glucosamine hyperimmune plasma to prevent R equi pneumonia in foals. J Vet Intern Med, 35 (6) (2021), pp. 2912-2919
[40]	N.D. Cohen, S.K. Kahn, C. Cywes-Bentley, S. Ramirez-Cortez, A.E. Schuckert, M. Vinacur, et al. Serum antibody activity against poly-N-acetyl glucosamine (PNAG), but not PNAG vaccination status, is associated with protecting newborn foals against intrabronchial infection with Rhodococcus equi. Microbiol Spectrum, 9 (1) (2021), Article e00638-21
[41]	J.N. Rocha, L.J. Dangott, W. Mwangi, R.C. Alaniz, A.I. Bordin, C. Cywes-Bentley, et al. PNAG-specific equine IgG1 mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG4/7. Vaccine, 37 (9) (2019), pp. 1142-1150
[42]	D. Skurnik, D. Roux, S. Pons, T. Guillard, X. Lu, C. Cywes-Bentley, et al.Extended-spectrum antibodies protective against carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother, 71 (4) (2016), pp. 927-935
[43]	N. Cerca, T. Maira-Litrán, K.K. Jefferson, M. Grout, D.A. Goldmann, G.B. Pier. Protection against Escherichia coli infection by antibody to the Staphylococcus aureus poly-N-acetylglucosamine surface polysaccharide. Proc Natl Acad Sci USA, 104 (18) (2007), pp. 7528-7533
[44]	M. Mellata, N.M. Mitchell, F. Schödel, R. Curtiss 3rd, G.B. Pier.Novel vaccine antigen combinations elicit protective immune responses against Escherichia coli sepsis. Vaccine, 34 (5) (2016), pp. 656-662
[45]	Lu X, Skurnik D, Pozzi C, Roux D, Cywes-Bentley C, Ritchie JM, et al. A poly-N-acetylglucosamine-Shiga toxin broad-spectrum conjugate vaccine for Shiga toxin-producing Escherichia coli. mBio 2014: 5(2):e00974-14.
[46]	L.V. Bentancor, J.M. O’Malley, C. Bozkurt-Guzel, G.B. Pier, T. Maira-Litrán. Poly-N-acetyl-β-(1-6)-glucosamine is a target for protective immunity against Acinetobacter baumannii infections. Infect Immun, 80 (2) (2012), pp. 651-666
[47]	J. Hülsdünker, O.S. Thomas, E. Haring, S. Unger, N.G. Núñez, S. Tugues, et al. Immunization against poly-N-acetylglucosamine reduces neutrophil activation and GVHD while sparing microbial diversity. Proc Natl Acad Sci USA, 116 (41) (2019), pp. 20700-20706
[48]	A. Kulp, M.J. Kuehn. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol, 64 (2010), pp. 163-184
[49]	A.R. Gorringe, R. Pajón. Bexsero: a multicomponent vaccine for prevention of meningococcal disease. Hum Vaccines Immunother, 8 (2) (2012), pp. 174-183
[50]	alopexx.com [Internet]. Cambridge: Alopexx incorporation; [cited 2023 Oct 10]. Available from: https://www.alopexx.com/pipeline/vaccine-av0328.
[51]	ClinicalTrials.gov [Internet]. Bethesda: National Library of Medicine; [cited 2023 Oct 10]. Available from: https://clinicaltrials.gov/study/NCT02853617.
[52]	C. Soliman, A.K. Walduck, E. Yuriev, J.S. Richards, C. Cywes-Bentley, G.B. Pier, et al. Structural basis for antibody targeting of the broadly expressed microbial polysaccharide poly-N-acetylglucosamine. J Biol Chem, 293 (14) (2018), pp. 5079-5089