Phospholipase A1 modulates the cell envelope phospholipid content of Brucella melitensis, contributing to polymyxin resistance and pathogenicity.
A subset of bacterial pathogens, including the zoonotic Brucella species, are highly resistant against polymyxin antibiotics. Bacterial polymyxin resistance has been attributed primarily to the modification of lipopolysaccharide; however, it is unknown what additional mechanisms mediate high-level resistance against this class of drugs. This work identified a role for the Brucella melitensis gene bveA (BMEII0681), encoding a predicted esterase, in the resistance of B. melitensis to polymyxin B. Characterization of the enzymatic activity of BveA demonstrated that it is a phospholipase A1 with specificity for phosphatidylethanolamine (PE). Further, lipidomic analysis of B. melitensis revealed an excess of PE lipids in the bacterial membranes isolated from the bveA mutant. These results suggest that by lowering the PE content of the cell envelope, BveA increases the resistance of B. melitensis to polymyxin B. BveA was required for survival and replication of B. melitensis in macrophages and for persistent infection in mice. BveA family esterases are encoded in the genomes of the alphaproteobacterial species that coexist with the polymyxin-producing bacteria in the rhizosphere, suggesting that maintenance of a low PE content in the bacterial cell envelope may be a shared persistence strategy for association with plant and mammalian hosts.
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Tobias
T
Kerrinnes
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Briana M
BM
Young
West Coast Metabolomics Center, University of California, Davis, Davis, California, USA.
Carlos
C
Leon
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Christelle M
CM
Roux
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Lisa
L
Tran
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Vidya L
VL
Atluri
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
Maria G
MG
Winter
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA rmtsolis@ucdavis.edu.
Renée M
RM
Tsolis
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017347:Brucella melitensis / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D010714:Phosphatidylethanolamines / Q000378:metabolism; D054466:Phospholipases A1 / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011113:Polymyxins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011113:Polymyxins; C483858:phosphatidylethanolamine; D054466:Phospholipases A1