Colistin Resistance in Acinetobacter baumannii Is Mediated by Complete Loss of Lipopolysaccharide Production

被引：609

作者：

Moffatt, Jennifer H. ^{[1
]}

Harper, Marina ^{[1
,2
]}

Harrison, Paul ^{[3
]}

Hale, John D. F. ^{[4
]}

Vinogradov, Evgeny ^{[5
]}

Seemann, Torsten ^{[3
]}

Henry, Rebekah ^{[1
]}

Crane, Bethany ^{[1
]}

Michael, Frank St. ^{[5
]}

Cox, Andrew D. ^{[5
]}

Adler, Ben ^{[1
,2
,3
]}

Nation, Roger L. ^{[4
]}

Li, Jian ^{[4
]}

Boyce, John D. ^{[1
,2
]}

机构：

[1] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia

[2] Monash Univ, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3800, Australia

[3] Monash Univ, Victorian Bioinformat Consortium, Clayton, Vic 3800, Australia

[4] Monash Univ, Facil Antiinfect Drug Dev & Innovat Drug Delivery, Monash Inst Pharmaceut Sci, Clayton, Vic 3800, Australia

[5] CNR, Inst Biol Sci, Ottawa, ON, Canada

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 12期

基金：

英国医学研究理事会;

关键词：

OUTER-MEMBRANE; POLYMYXIN-B; 1ST STEP; HETERORESISTANCE; EMERGENCE; INSERTION; IDENTIFICATION; ANTIBIOTICS; MENINGITIS; BACTERIUM;

D O I：

10.1128/AAC.00834-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Infections caused by multidrug-resistant (MDR) Gram-negative bacteria represent a major global health problem. Polymyxin antibiotics such as colistin have resurfaced as effective last-resort antimicrobials for use against MDR Gram-negative pathogens, including Acinetobacter baumannii. Here we show that A. baumannii can rapidly develop resistance to polymyxin antibiotics by complete loss of the initial binding target, the lipid A component of lipopolysaccharide (LPS), which has long been considered to be essential for the viability of Gram-negative bacteria. We characterized 13 independent colistin-resistant derivatives of A. baumannii type strain ATCC 19606 and showed that all contained mutations within one of the first three genes of the lipid A biosynthesis pathway: lpxA, lpxC, and lpxD. All of these mutations resulted in the complete loss of LPS production. Furthermore, we showed that loss of LPS occurs in a colistin-resistant clinical isolate of A. baumannii. This is the first report of a spontaneously occurring, lipopolysaccharide-deficient, Gram-negative bacterium.

引用

页码：4971 / 4977

页数：7

共 39 条

[1] Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System [J].

Adams, Mark D. ;

Nickel, Gabrielle C. ;

Bajaksouzian, Saralee ;

Lavender, Heather ;

Murthy, A. Rekha ;

Jacobs, Michael R. ;

Bonomo, Robert A. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (09) :3628-3634

[2]

[Anonymous], 2012, Molecular Cloning: A Laboratory Manual

[3] Identification of Novel Glycosyltransferases Required for Assembly of the Pasteurella multocida A:1 Lipopolysaccharide and Their Involvement in Virulence [J].

Boyce, John D. ;

Harper, Marina ;

Michael, Frank St. ;

John, Marietta ;

Aubry, Annie ;

Parnas, Henrietta ;

Logan, Susan M. ;

Wilkie, Ian W. ;

Ford, Mark ;

Cox, Andrew D. ;

Adler, Ben .

INFECTION AND IMMUNITY, 2009, 77 (04) :1532-1542

[4] Selection of colistin-resistant Acinetobacter baumannii isolates in postneurosurgical meningitis in an intensive care unit with high presence of heteroresistance to colistin [J].

Carlos Hernan, Rodriguez ;

Karina, Bombicino ;

Gabriela, Granados ;

Marcela, Nastro ;

Carlos, Vay ;

Angela, Famiglietti .

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2009, 65 (02) :188-191

[5] Gram-negative outer and inner membrane models: Insertion of cyclic cationic lipopeptides [J].

Clausell, Adria ;

Garcia-Subirats, Maria ;

Pujol, Montserrat ;

Busquets, M. Antonia ;

Rabanal, Francesc ;

Cajal, Yolanda .

JOURNAL OF PHYSICAL CHEMISTRY B, 2007, 111 (03) :551-563

[6]

Clinical and Laboratory Standards Institute, 2008, M100S18 CLIN LAB STA

[7] Genetic and phenotypic analysis of Acinetobacter baumannii insertion derivatives generated with a transposome system [J].

Dorsey, CW ;

Tomaras, AP ;

Actis, LA .

APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2002, 68 (12) :6353-6360

[8] Polymyxin B sulfate and colistin: Old antibiotics for emerging multiresistant gram-negative bacteria [J].

Evans, ME ;

Feola, DJ ;

Rapp, RP .

ANNALS OF PHARMACOTHERAPY, 1999, 33 (09) :960-967

[9] Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004) [J].

Gales, AC ;

Jones, RN ;

Sader, HS .

CLINICAL MICROBIOLOGY AND INFECTION, 2006, 12 (04) :315-321

[10]

GALLOWAY SM, 1990, J BIOL CHEM, V265, P6394

← 1 2 3 4 →