Meningococcal resistance to antimicrobial peptides is mediated by bacterial adhesion and host cell RhoA and Cdc42 signalling
2013 (English)In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 11, 1938-1954 p.Article in journal (Refereed) Published
Antimicrobial peptides (AMPs) constitute an essential part of the innate immune defence. Pathogenic bacteria have evolved numerous strategies to withstand AMP-mediated killing. The influence of host epithelia on bacterial AMP resistance is, however, still largely unknown. We found that adhesion to pharyngeal epithelial cells protected Neisseria meningitidis, a leading cause of meningitis and sepsis, from the human cathelicidin LL-37, the cationic model amphipathic peptide (MAP) and the peptaibol alamethicin, but not from polymyxin B. Adhesion to primary airway epithelia resulted in a similar increase in LL-37 resistance. The inhibition of selective host cell signalling mediated by RhoA and Cdc42 was found to abolish the adhesion-induced LL-37 resistance by a mechanism unrelated to the actin cytoskeleton. Moreover, N. meningitidis triggered the formation of cholesterol-rich membrane microdomains in pharyngeal epithelial cells, and host cell cholesterol proved to be essential for adhesion-induced resistance. Our data highlight the importance of Rho GTPase-dependent host cell signalling for meningococcal AMP resistance. These results indicate that N. meningitidis selectively exploits the epithelial microenvironment in order to protect itself from LL-37.
Place, publisher, year, edition, pages
2013. Vol. 15, no 11, 1938-1954 p.
Microbiology Cell and Molecular Biology
Research subject Molecular Biosciences
IdentifiersURN: urn:nbn:se:su:diva-92688DOI: 10.1111/cmi.12163ISI: 000325541700012OAI: oai:DiVA.org:su-92688DiVA: diva2:640888
Swedish Research Council; Swedish Cancer Society; Ragnar Söderbergs Stiftelse; Knut and Alice Wallenbergs Stiftelse; Torsten Söderbergs Stiftelse 2013-08-142013-08-142014-01-15Bibliographically approved