Dataset Information

Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant Staphylococcus aureus Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.

ABSTRACT: Staphylococcus aureus is a major opportunistic pathogen, infecting animals, and human beings. The bacterial cell wall plays a crucial role in antimicrobial resistance and its infection to host cells. Peptidoglycans (PGs) are a major component of the cell wall in S. aureus, which is heavily decorated with wall teichoic acids (WTAs) and capsular polysaccharides (CPs). The ligation of WTAs and CPs to PGs is catalyzed by LytR-CpsA-Psr (LCP) family proteins, including LcpA, LcpB, and LcpC. However, the involvement of LcpC in antimicrobial resistance of S. aureus and its infection to host cells remains unknown. By creating the LcpC-knockout strains, we showed that the deficiency in LcpC decreased the antimicrobial resistance to ?-lactams and glycopeptides and impeded the binding to various epithelial cells. These changes were accompanied by the morphological changes in bacterial cell wall. More importantly, the knockout of LcpC significantly reduced the pathogenicity of methicillin-resistant S. aureus (MRSA) in mice. Our results suggest that LcpC might be an appealing target for developing a therapeutic approach against MRSA infections.

SUBMITTER: Li F

PROVIDER: S-EPMC7212477 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant Staphylococcus aureus Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.

Li Fan F Zhai Dongsheng D Wu Zhaowei Z Zhao Yan Y Qiao Dandan D Zhao Xin X

Frontiers in microbiology 20200416

Staphylococcus aureus is a major opportunistic pathogen, infecting animals, and human beings. The bacterial cell wall plays a crucial role in antimicrobial resistance and its infection to host cells. Peptidoglycans (PGs) are a major component of the cell wall in S. aureus, which is heavily decorated with wall teichoic acids (WTAs) and capsular polysaccharides (CPs). The ligation of WTAs and CPs to PGs is catalyzed by LytR-CpsA-Psr (LCP) family proteins, including LcpA, LcpB, and Lc ...[more]

PMID: 32425893

Similar Datasets

Project description:Proteins of the LCP (LytR, CpsA, Psr) family have been shown to inherit important roles in bacterial cell wall biosynthesis. However, their exact function in the formation of the complex cell wall structures of the Corynebacteriales, including the prominent pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae, remains unclear. Here, we analyzed the role of the LCP proteins LcpA and LcpB of Corynebacterium glutamicum, both of which localize at regions of nascent cell wall biosynthesis. A strain lacking lcpB did not show any growth-related or morphological phenotype under the tested conditions. In contrast, conditional silencing of the essential lcpA gene resulted in severe growth defects and drastic morphological changes. Compared to the wild-type cell wall, the cell wall of this mutant contained significantly less mycolic acids and a reduced amount of arabinogalactan. In particular, rhamnose, a specific sugar component of the linker that connects arabinogalactan and peptidoglycan, was decreased. Complementation studies of the lcpA-silencing strain with several mutated and truncated LcpA variants suggested that both periplasmic domains are essential for function whereas the cytoplasmic N-terminal part is dispensable. Successful complementation experiments with proteins of M. tuberculosis and C. diphtheriae revealed a conserved function of LCP proteins in these species. Finally, pyrophosphatase activity of LcpA was shown in an in vitro assay. Taken together, our results suggest that LCP proteins are responsible for the transfer of arabinogalactan onto peptidoglycan in actinobacterial species and support a crucial function of a so-far-uncharacterized C-terminal domain (LytR_C domain) which is frequently found at the C terminus of the LCP domain in this prokaryotic phylum.ImportanceAbout one-third of the world's population is infected with Mycobacterium tuberculosis, and multiple-antibiotic resistance provokes the demand for novel antibiotics. The special cell wall architecture of Corynebacteriales is critical for treatments because it is either a direct target or a barrier that the drug has to cross. Here, we present the analysis of LcpA and LcpB of the closely related Corynebacterium glutamicum, the first of which is an essential protein involved in cell wall biogenesis. Our work provides a comprehensive characterization of the impact of LCP proteins on cell wall biogenesis in this medically and biotechnologically important class of bacteria. Special focus is set on the two periplasmic LcpA domains and their contributions to physiological function.

Dataset Information

Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant Staphylococcus aureus Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.

Publications

Impairment of the Cell Wall Ligase, LytR-CpsA-Psr Protein (LcpC), in Methicillin Resistant <i>Staphylococcus aureus</i> Reduces Its Resistance to Antibiotics and Infection in a Mouse Model of Sepsis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets