Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa

被引：28

作者：

Romano, Keith P. ^{[1
,2
,3
]}

Warrier, Thulasi ^{[1
,2
]}

Poulsen, Bradley E. ^{[1
,2
,4
]}

Nguyen, Phuong H. ^{[1
,2
,4
]}

Loftis, Alexander R. ^{[5
]}

Saebi, Azin ^{[5
]}

Pentelute, Bradley L. ^{[5
]}

Hung, Deborah T. ^{[1
,2
,4
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Massachusetts Gen Hosp, Dept Mol Biol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[3] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA

[4] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[5] MIT, Dept Chem, Cambridge, MA 02139 USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2019年 / 63卷 / 09期

关键词：

murepavadin; POL7001; POL7080; Pseudomonas; antibiotic resistance; colistin; multidrug resistance; pmrB; polymyxins; CATIONIC ANTIMICROBIAL PEPTIDES; 2-COMPONENT REGULATORY SYSTEM; OUTER-MEMBRANE; POLYMYXIN RESISTANCE; ANTIBIOTICS; PENETRATION; BACTERIA;

D O I：

10.1128/AAC.00511-19

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene pmrB. Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding.

引用

页数：6

共 2 条

[1] PmrB Mutations Promote Polymyxin Resistance of Pseudomonas aeruginosa Isolated from Colistin-Treated Cystic Fibrosis Patients
Moskowitz, Samuel M.
Brannon, Mark K.
Dasgupta, Nandini
Pier, Miyuki
Sgambati, Nicole
Miller, Amanda K.
Selgrade, Sara E.
Miller, Samuel I.
Denton, Miles
Conway, Steven P.
Johansen, Helle K.
Hoiby, Niels
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2012, 56 (02) : 1019 - 1030
[2] In vivo divergent evolution of cross-resistance to new β-lactam/β-lactamase inhibitor combinations in Pseudomonas aeruginosa following ceftazidime/avibactam treatment
Cai, Heng
Chen, Minhua
Li, Yue
Wang, Nanfei
Ni, Hanming
Zhang, Piaopiao
Hua, Xiaoting
Yu, Yunsong
INFECTION, 2024, : 635 - 647

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