Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila

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Boamah, DavidDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States (author)

Peptidoglycan deacetylation controls type IV secretion and the intracellular survival of the bacterial pathogen Legionella pneumophila

Article/chapterEnglish2023

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Proceedings of the National Academy of Sciences (PNAS),2023
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LIBRIS-ID:oai:DiVA.org:umu-209548
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-209548URI
https://doi.org/10.1073/pnas.2119658120DOI

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Language:English
Summary in:English

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Peptidoglycan is a critical component of the bacteria cell envelope. Remodeling of the peptidoglycan is required for numerous essential cellular processes and has been linked to bacterial pathogenesis. Peptidoglycan deacetylases that remove the acetyl group of the N-acetylglucosamine (NAG) subunit protect bacterial pathogens from immune recognition and digestive enzymes secreted at the site of infection. However, the full extent of this modification on bacterial physiology and pathogenesis is not known. Here, we identify a polysaccharide deacetylase of the intracellular bacterial pathogen Legionella pneumophila and define a two-tiered role for this enzyme in Legionella pathogenesis. First, NAG deacetylation is important for the proper localization and function of the Type IVb secretion system, linking peptidoglycan editing to the modulation of host cellular processes through the action of secreted virulence factors. As a consequence, the Legionella vacuole mis-traffics along the endocytic pathway to the lysosome, preventing the formation of a replication permissive compartment. Second, within the lysosome, the inability to deacetylate the peptidoglycan renders the bacteria more sensitive to lysozyme-mediated degradation, resulting in increased bacterial death. Thus, the ability to deacetylate NAG is important for bacteria to persist within host cells and in turn, Legionella virulence. Collectively, these results expand the function of peptidoglycan deacetylases in bacteria, linking peptidoglycan editing, Type IV secretion, and the intracellular fate of a bacterial pathogen.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Mikrobiologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Microbiology in the medical area hsv//eng
NATURVETENSKAP Biologi Mikrobiologi hsv//swe
NATURAL SCIENCES Biological Sciences Microbiology hsv//eng
DotK
Legionella
peptidoglycan
polysaccharide deacetylase
type IV secretion system

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Gilmore, Michael C.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)migi0012 (author)
Bourget, SarahDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States (author)
Ghosh, AnushkaDepartment of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States (author)
Hossain, Mohammad J.Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States (author)
Vogel, Joseph P.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States (author)
Cava, FelipeUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)feca0003 (author)
O'Connor, Tamara J.Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United States (author)
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, United StatesMolekylär Infektionsmedicin, Sverige (MIMS) (creator_code:org_t)

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In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences (PNAS)120:230027-84241091-6490

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By the author/editor: Boamah, David; Gilmore, Michael ...; Bourget, Sarah; Ghosh, Anushka; Hossain, Mohamma ...; Vogel, Joseph P.; show more...; Cava, Felipe; O'Connor, Tamara ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Microbiology

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