Unified Theory of Bacterial Sialometabolism: How and Why Bacteria Metabolize Host Sialic Acids

Abstract

Sialic acids are structurally diverse nine-carbon ketosugars found mostly in humans and other animals as the terminal units on carbohydrate chains linked to proteins or lipids. The sialic acids function in cell-cell and cell-molecule interactions necessary for organismic development and homeostasis. They not only pose a barrier to microorganisms inhabiting or invading an animal mucosal surface, but also present a source of potential carbon, nitrogen, and cell wall metabolites necessary for bacterial colonization, persistence, growth, and, occasionally, disease. The explosion of microbial genomic sequencing projects reveals remarkable diversity in bacterial sialic acid metabolic potential. How bacteria exploit host sialic acids includes a surprisingly complex array of metabolic and regulatory capabilities that is just now entering a mature research stage. This paper attempts to describe the variety of bacterial sialometabolic systems by focusing on recent advances at the molecular and host-microbe-interaction levels. The hope is that this focus will provide a framework for further research that holds promise for better understanding of the metabolic interplay between bacterial growth and the host environment. An ability to modify or block this interplay has already yielded important new insights into potentially new therapeutic approaches for modifying or blocking bacterial colonization or infection.

Unexpected Diversity of Escherichia coli Sialate O -Acetyl Esterase NanS

“…express nanS with resulting O-acetylesterase activity. The combined results support the hypothesis that sialometabolism of sialic acids other than Neu5Ac might be important to a wide range of host-bacterium interactions (8).…”

“…We previously documented the wide variety of nan gene organizations in different bacterial commensals and pathogens (8). Most of these species, though not all, include one or more copies of nanS.…”

“…Therefore, blocking bacterial access to host sialic acids could have therapeutic benefit (9,10). However, all studies to date have been focused on the metabolism of Neu5Ac, the most common sialic acid, despite evidence that it is just one of several chemically distinct forms of sialic acid attached to host glycoconjugates (8). A recent study from this laboratory showed that Escherichia coli uses O-acetylated sialic acid as a sole source of carbon (11), and that this metabolic capability is dependent on a sialate, O-acetyl esterase (NanS), which is coordinately regulated by the NanR transcription repressor controlling expression of the sialoregulon (5,12).…”

Aeromonas salmonicida Growth in Response to Atlantic Salmon Mucins Differs between Epithelial Sites, Is Governed by Sialylated and N -Acetylhexosamine-Containing O -Glycans, and Is Affected by Ca 2+

“…We previously demonstrated that Neu5Ac is an important part of the epitope to which A. salmonicida adheres (22), and we have demonstrated here that Neu5Ac shields mucins from promoting growth of this pathogen. Numerous bacteria are able to use sialic acids as a carbon and energy source (40). The literature provides no evidence that A. salmonicida possesses any genes for sialidase enzymes, and the results showing that A. salmonicida growth increased after removal of sialic acids from the mucins, as well as A. salmonicida's inability to cleave 4MU-Neu5Ac, support that A. salmonicida lacks the ability to cleave and subsequently utilize mucinlinked Neu5Ac.…”

Transcription of Sialic Acid Catabolism Genes in Corynebacterium glutamicum Is Subject to Catabolite Repression and Control by the Transcriptional Repressor NanR

“…Besides serving as attachment and recognition point for various pathogens, Neu5Ac is also an important source of carbon and energy available in various host niches such as the oral cavity and the respiratory, intestinal, and urogenital tracts (29)(30)(31)(32). Therefore, Neu5Ac metabolism and its control have been studied in detail for various, often pathogenic, bacteria such as Escherichia coli, Vibrio vulnificus, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Clostridium perfringens, and the probiotic Bifidobacterium breve (33)(34)(35)(36)(37)(38).…”