Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance

TY - JOUR

T1 - Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance

AU - Heise, Torben

AU - Langereis, Jeroen D

AU - Rossing, Emiel

AU - de Jonge, Marien I

AU - Adema, Gosse J

AU - Büll, Christian

AU - Boltje, Thomas J

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/10/18

Y1 - 2018/10/18

N2 - Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry. Molecular mimicry of non-typeable Haemophilus influenzae (NTHi) with host sialic acid sugars mediates resistance to serum killing and increases virulence. Heise et al. have developed sialic acid derivatives that allow either visualization or inhibition of host sialic acid transfer to NTHi, the latter enhancing serum-mediated killing.

AB - Pathogens such as non-typeable Haemophilus influenzae (NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in an in vitro model of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry. Molecular mimicry of non-typeable Haemophilus influenzae (NTHi) with host sialic acid sugars mediates resistance to serum killing and increases virulence. Heise et al. have developed sialic acid derivatives that allow either visualization or inhibition of host sialic acid transfer to NTHi, the latter enhancing serum-mediated killing.

U2 - 10.1016/j.chembiol.2018.05.018

DO - 10.1016/j.chembiol.2018.05.018

M3 - Journal article

C2 - 29983272

SN - 2451-9448

VL - 25

SP - 1279

EP - 1285

JO - Cell Chemical Biology

JF - Cell Chemical Biology

IS - 10

ER -