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Biology subjects

Bastos, P. A. D.

Publications and source records attributed to Bastos, P. A. D..

2 recordsLinked to original sources

Microbiota-induced active translocation of peptidoglycan across the intestinal barrier dictates its within-host dissemination

Peptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.

microbiology↗

Crippling the bacterial cell wall molecular machinery

Lytic transglycosylases (LT) are redundant enzymes that play a critical role in peptidoglycan (PG) recycling and metabolism. LT(s) role in cell wall-modifying complexes and usefulness as antimicrobial drug targets remain elusive. We determined at high-resolution a structure of the membrane-bound homolog of the soluble LT from Neisseria species with a disordered active site helix (alpha helix 30). Alpha helix 30 is crucial for binding PG during catalysis1. Here we show using an alpha helix 30 deletion strain that LT (LtgA) determines the integrity of the cell wall, participates in cell division and separation, and can be manipulated to impair the fitness of the human pathogen Neisseria meningitidis during infection. Characterization of ltgA helix deleted strain interactome identified glycan chain remodeling enzymes whose function appear to be modulated by LTs. Targeting LTs can disrupt the PG machinery, which is fatal for the bacterium, a new approach for antibiotic development.

biochemistry↗