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    LysX2 is a Mycobacterium tuberculosis membrane protein with an extracytoplasmic MprF-like domain.

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    Author
    Boldrin, Francesca
    Cioetto Mazzabò, Laura
    Lanéelle, Marie-Antoinette
    Rindi, Laura
    Segafreddo, Greta
    Lemassu, Anne
    Etienne, Gilles
    Conflitti, Marta
    Daffé, Mamadou
    Garzino Demo, Alfredo
    Manganelli, Riccardo
    Marrakchi, Hedia
    Provvedi, Roberta
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    Date
    2022-04-01
    Journal
    BMC Microbiology
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1186/s12866-022-02493-2
    Abstract
    Background: Aminoacyl-phosphatidylglycerol (aaPG) synthases are bacterial enzymes that usually catalyze transfer of aminoacyl residues to the plasma membrane phospholipid phosphatidylglycerol (PG). The result is introduction of positive charges onto the cytoplasmic membrane, yielding reduced affinity towards cationic antimicrobial peptides, and increased resistance to acidic environments. Therefore, these enzymes represent an important defense mechanism for many pathogens, including Staphylococcus aureus and Mycobacterium tuberculosis (Mtb), which are known to encode for lysyl-(Lys)-PG synthase MprF and LysX, respectively. Here, we used a combination of bioinformatic, genetic and bacteriological methods to characterize a protein encoded by the Mtb genome, Rv1619, carrying a domain with high similarity to MprF-like domains, suggesting that this protein could be a new aaPG synthase family member. However, unlike homologous domains of MprF and LysX that are positioned in the cytoplasm, we predicted that the MprF-like domain in LysX2 is in the extracytoplasmic region. Results: Using genetic fusions to the Escherichia coli proteins PhoA and LacZ of LysX2, we confirmed this unique membrane topology, as well as LysX and MprF as benchmarks. Expression of lysX2 in Mycobacterium smegmatis increased cell resistance to human β-defensin 2 and sodium nitrite, enhanced cell viability and delayed biofilm formation in acidic pH environment. Remarkably, MtLysX2 significantly reduced the negative charge on the bacterial surface upon exposure to an acidic environment. Additionally, we found LysX2 orthologues in major human pathogens and in rapid-growing mycobacteria frequently associated with human infections, but not in environmental and non-pathogenic mycobacteria. Conclusions: Overall, our data suggest that LysX2 is a prototype of a new class within the MprF-like protein family that likely enhances survival of the pathogenic species through its catalytic domain which is exposed to the extracytoplasmic side of the cell membrane and is required to decrease the negative charge on the bacterial surface through a yet uncharacterized mechanism.
    Rights/Terms
    © 2022. The Author(s).
    Keyword
    Acidic pH
    Aminoacyl-phosphatidylglycerol synthase
    Antimicrobial peptides
    Biofilm
    LysX
    MprF
    Mycobacteria
    Tuberculosis
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18452
    ae974a485f413a2113503eed53cd6c53
    10.1186/s12866-022-02493-2
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