Abstract
The cell surface is the primary recognition site between the bacterium and the host. An operon of three genes, LSEI_0219 (cwaR), LSEI_0220 (cwaS), and LSEI_0221 (ldcA), has been previously identified as required for the establishment of Lactobacillus paracasei in the gut. The genes cwaR and cwaS encode a predicted two-component system (TCS) and ldcA a predicted D-alanyl-D-alanine carboxypeptidase which is a peptidoglycan (PG) biosynthesis enzyme. We explored the functionality and the physiological role of these three genes, particularly their impact on the bacterial cell wall architecture and on the bacterial adaptation to environmental perturbations in the gut. The functionality of CwaS/R proteins as a TCS has been demonstrated by biochemical analysis. It is involved in the transcriptional regulation of several genes of the PG biosynthesis. Analysis of the muropeptides of PG in mutants allowed us to re-annotate LSEI_0221 as a putative L,D-carboxypeptidase (LdcA). The absence of this protein coincided with a decrease of two surface antigens: LSEI_0020, corresponding to p40 or msp2 whose implication in the host epithelial homeostasis has been recently studied, and LSEI_2029 which has never been functionally characterized. The inactivation of each of these three genes induces susceptibility to antimicrobial peptides (hBD1, hBD2, and CCL20), which could be the main cause of the gut establishment deficiency. Thus, this operon is necessary for the presence of two surface antigens and for a suitable cell wall architecture.
Highlights
Advances in metagenomics have highlighted the diversity of functions encoded by the microbiota, the variability of the microbiota composition between individuals, and the link between gut microbiota composition and chronic diseases, cancer, and obesity (Arumugam et al, 2011; Lozupone et al, 2012; The Human Microbiome Project Consortium, 2012; Sonnenburg and Bäckhed, 2016; Zitvogel et al, 2017)
The cwaR gene (LSEI_0219) belongs to the OmpR family and is a predicted response regulator (RR); the cwaS gene (LSEI_0220) is a predicted signal transduction histidine kinase (HK); the ldcA gene (LSEI_0221) is a predicted D-Ala-DAla carboxypeptidase. This family of two-component system (TCS) is widely encountered in the bacterial world
The TCS genes can be followed by a D-Ala-DAla carboxypeptidase as in L. paracasei or by another putative operon composed of murE (UDP-N-acteylmuramoylalanylD-glutamate-2,6-diaminopimelate ligase) and racD
Summary
Advances in metagenomics have highlighted the diversity of functions encoded by the microbiota, the variability of the microbiota composition between individuals, and the link between gut microbiota composition and chronic diseases, cancer, and obesity (Arumugam et al, 2011; Lozupone et al, 2012; The Human Microbiome Project Consortium, 2012; Sonnenburg and Bäckhed, 2016; Zitvogel et al, 2017). As natural inhabitants of fermented food and feed (plants, meat, dairy), as well as the oral cavity, gut, and genital tracts, Lactobacillus species share a good genetic arsenal to fit new and sometimes harsh environments (Makarova et al, 2006; Fiocco et al, 2019) Their high adaptability to environmental perturbations results from an accurate coordination of cellular processes (production of chaperones and DNA repair proteins, induction of metabolic pathways or transport systems, modifications of membrane composition) mediated by networks of regulators and two-component systems (TCSs) (van de Guchte et al, 2002). The cell wall of Lactobacillus is composed of a PG layer decorated with teichoic acids and anchored proteins like PG hydrolases and LPxTG proteins that surround the cytoplasmic membrane
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