Severe Central Nervous System Co-infection With Streptococcus pneumoniae and Varicella-Zoster Virus Presenting as Meningoencephalitis.

The human gastrointestinal (GI) tract is home to a wide array of microbes, collectively termed the human gut microbiota (HGM). Intense research efforts over the past 2 decades have revealed that this bacteria-dominated community has far-reaching effects on human health. Complex dietary glycans (“fibre”) that cannot be degraded by enzymes of the human digestive tract are thought to be the primary nutrient source for the HGM, and the utilisation of these complex sugars is crucial for the relationship between host and bacteria, leading, for example, to the generation of short-chain fatty acids that provide metabolic energy and systemic health benefits to the host. The colon or large intestine is the most densely populated part of the GI tract, with microbial densities up to 10–10 per gram of luminal content (). Most of the colonic microbiota belongs to two bacterial phyla: the Gram-positive Bacillota and the Gram-negative Bacteroidota. Additional, minor phyla include Actinomycetota and Pseudomonadota (; ; ). Belonging to the Bacteroidota, members of the genus have attracted particular attention for several reasons. First, several species (, ) (; ) are relatively easy to culture in the lab and can be manipulated genetically. Second, the are collectively the most abundant bacterial genus in the gut of western world populations, comprising up to 40% of all bacteria in the large intestine (). As such, play an important role in shaping the HGM, and their study can be expected to yield important discoveries on fundamental aspects of the gut microbial ecosystem. Third, Bacteroides are prolific, primary degraders of many dietary glycans, producing many oligosaccharides that can be used by other members of the HGM, a phenomenon called cross-feeding. The best-studied member of the , VPI-5482 , is considered a glycan “generalist” owing to the ∼18% of its 6.2 Mb genome that is dedicated to the utilisation of glycans (; ). The -transcribed genes involved in the degradation of a particular glycan are organised on the genome in so-called PULs (polysaccharide utilisation loci). According to the PUL database (), has 86 predicted PULs, and for most of these no ligands have been identified experimentally. PUL prediction is based on the presence of at least one SusCD pair, consisting of a SusC (from tarch tilisation ystem or accharide tilisation ystem) TonB-dependent transporter (TBDT) and a tightly associated SusD ligand binding protein. SusDs are surface-exposed lipoproteins (SLPs) that form a mobile cap on the SusC transporter to deliver transport-competent substrates to the SusC via a “pedal-bin” mechanism (; ; ). In addition to SusD proteins, PULs typically include additional SLPs such as surface glycan binding proteins (SGBPs) and glycoside hydrolases (GHs), involved in the initial binding of polymeric glycans and degradation of those glycans into transport-competent oligosaccharides, respectively (; ). It should be noted that approximately a quarter of predicted PULs do not contain proteins with obvious glycan binding or degradation functionalities, suggesting that non-glycan molecules such as peptides () are also taken up by “PULs”.