Porphyromonas gingivalis resistance to polymyxin B is determined by the lipid A 4'-phosphatase, PGN_0524.

International Journal of Oral Science
Stephen R CoatsRichard P Darveau

Abstract

To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis (P. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin B. A genetic screen of P. gingivalis clones generated by a Tn4400'-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B (PMB, 50 microg x mL(-1)). P. gingivalis (ATCC 33277) is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations (200 microg x mL(-1)). Approximately 2,700 independent Tn4400'-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 microg x mL(-1)). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400' transposon was integrated into the gene encoding the lipid A 4'-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400', was highly sensitive to PMB killing relative to wild-t...Continue Reading

Citations

Aug 28, 2010·Biochemistry·Brian O IngramChristian R H Raetz
May 1, 2015·Antibiotics·Victor I Band, David S Weiss
Dec 1, 2009·Journal of Zhejiang University. Science. B·Mei-ying ShaoTao Hu
Jun 12, 2013·Nature Reviews. Microbiology·Brittany D Needham, M Stephen Trent
Apr 8, 2020·Infection and Immunity·Nicole P GiordanoZachary D Dalebroux
Jul 13, 2021·Genomics, Proteomics & Bioinformatics·Zhenwei LiuXiaobing Wang

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