Phospholipase A1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity

Tobias Kerrinnes, Briana M. Young, Carlos Leon, Christelle M. Roux, Lisa Tran, Vidya L. Atluri, Maria G. Winter, Renee M Tsolis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 poly-myxin-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.

Original languageEnglish (US)
Pages (from-to)6717-6724
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

Phospholipases A1
Polymyxins
Brucella melitensis
Virulence
Phospholipids
Polymyxin B
Esterases
Brucella
Rhizosphere
Zoonoses
Lipopolysaccharides
Macrophages
Maintenance
Genome
Anti-Bacterial Agents
Bacteria
Lipids
Membranes
phosphatidylethanolamine
Infection

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Phospholipase A1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity. / Kerrinnes, Tobias; Young, Briana M.; Leon, Carlos; Roux, Christelle M.; Tran, Lisa; Atluri, Vidya L.; Winter, Maria G.; Tsolis, Renee M.

In: Antimicrobial Agents and Chemotherapy, Vol. 59, No. 11, 01.11.2015, p. 6717-6724.

Research output: Contribution to journalArticle

Kerrinnes, Tobias ; Young, Briana M. ; Leon, Carlos ; Roux, Christelle M. ; Tran, Lisa ; Atluri, Vidya L. ; Winter, Maria G. ; Tsolis, Renee M. / Phospholipase A1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity. In: Antimicrobial Agents and Chemotherapy. 2015 ; Vol. 59, No. 11. pp. 6717-6724.
@article{2c088b89aa4e42f4ab88532beee20472,
title = "Phospholipase A1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity",
abstract = "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 poly-myxin-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.",
author = "Tobias Kerrinnes and Young, {Briana M.} and Carlos Leon and Roux, {Christelle M.} and Lisa Tran and Atluri, {Vidya L.} and Winter, {Maria G.} and Tsolis, {Renee M}",
year = "2015",
month = "11",
day = "1",
doi = "10.1128/AAC.00792-15",
language = "English (US)",
volume = "59",
pages = "6717--6724",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Phospholipase A1 modulates the cell envelope phospholipid content of brucella melitensis, contributing to polymyxin resistance and pathogenicity

AU - Kerrinnes, Tobias

AU - Young, Briana M.

AU - Leon, Carlos

AU - Roux, Christelle M.

AU - Tran, Lisa

AU - Atluri, Vidya L.

AU - Winter, Maria G.

AU - Tsolis, Renee M

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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 poly-myxin-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.

AB - 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 poly-myxin-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.

UR - http://www.scopus.com/inward/record.url?scp=84946198866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946198866&partnerID=8YFLogxK

U2 - 10.1128/AAC.00792-15

DO - 10.1128/AAC.00792-15

M3 - Article

C2 - 26282427

AN - SCOPUS:84946198866

VL - 59

SP - 6717

EP - 6724

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 11

ER -