Nontypeable Haemophilus influenzae Has Evolved Preferential Use of N- Acetylneuraminic Acid as a Host Adaptation

• DOI: 10.1128/mbio.00422-19
• Publication Date: 2019-05-06T18:09:19Z
• Authors: Preston S. K. Ng; Christopher J. Day; John M. Atack; Lauren E. Hartley...; Linda E. Winter; Tal Marshanski; Vered Padler-Kara...; Ajit Varki; Stephen J. Barenkamp; Michael A. Apicella; Michael P. Jennings
• Keywords: 0301 basic medicine; 570; Host Microbial Interactions; Cell Membrane; bacterial metabolism; 610; microbial pathogenesis; Medical microbiology; Microbiology; Adaptation, Physiological; Haemophilus influenzae; QR1-502; N-Acetylneuraminic Acid; Substrate Specificity; 3. Good health; 03 medical and health sciences; glycobiology; sialic acid; Biochemistry and cell biology; Sialic Acids; Humans; Research Article; Immune Evasion

Host-adapted bacterial pathogens such as NTHi cannot survive out of their host environment and have evolved host-specific mechanisms to obtain nutrients and evade the immune response. Relatively few of these host adaptations have been characterized at the molecular level. NTHi utilizes sialic acid as a nutrient and also incorporates this sugar into LOS, which is important in biofilm formation and immune evasion. In the present study, we showed that NTHi has evolved to preferentially utilize the Neu5Ac form of sialic acid. This adaptation is due to the substrate preference of the enzyme CMP-Neu5Ac synthetase, which synthesizes the activated form of Neu5Ac for macromolecule biosynthesis. This adaptation allows NTHi to evade killing by a human antibody response against the nonhuman sialic acid Neu5Gc.