Overcoming addition of phosphoethanolamine to lipid A mediated colistin resistance in Acinetobacter baumannii clinical isolates with colistin-sulbactam combination therapy

被引：31

作者：

Srisakul, Sukrit ^{[1
,2
]}

Wannigama, Dhammika Leshan ^{[1
,2
,4
,9
]}

Higgins, Paul G. ^{[5
,6
,7
]}

Hurst, Cameron ^{[8
,23
]}

Abe, Shuichi ^{[9
,23
]}

Hongsing, Parichart ^{[10
,11
,23
]}

Saethang, Thammakorn ^{[12
]}

Luk-in, Sirirat ^{[1
,13
]}

Liao, Tingting ^{[14
,15
]}

Kueakulpattana, Naris ^{[1
,2
]}

Shein, Aye Mya Sithu ^{[1
,2
,3
]}

Gan, Lin ^{[16
]}

Kupwiwat, Rosalyn ^{[17
,23
]}

Tanasatitchai, Chanikan ^{[1
,2
,23
]}

Wapeesittipan, Pattama ^{[18
,23
]}

Phattharapornjaroen, Phatthranit ^{[19
,20
,23
]}

Badavath, Vishnu Nayak ^{[21
,23
]}

Leelahavanichkul, Asada ^{[1
,22
]}

Chatsuwan, Tanittha ^{[1
,2
,23
]}

机构：

[1] Chulalongkorn Univ, King Chulalongkorn Mem Hosp, Dept Microbiol, Fac Med,Thai Red Cross Soc, 1873 Rama 4 Rd, Bangkok 10330, Thailand

[2] Chulalongkorn Univ, Ctr Excellence Antimicrobial Resistance & Steward, Fac Med, Bangkok, Thailand

[3] Chulalongkorn Univ, Grad Sch, Interdisciplinary Program Med Microbiol, Bangkok, Thailand

[4] Univ Western Australia, Sch Med, Fac Hlth & Med Sci, Nedlands, WA, Australia

[5] Univ Cologne, Inst Med Microbiol Immunol & Hyg, Fac Med, Cologne, Germany

[6] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[7] German Ctr Infect Res, Partner Site Bonn Cologne, Cologne, Germany

[8] QIMR Berghofer Med Res Inst, Stat, Brisbane, Qld, Australia

[9] Yamagata Prefectural Cent Hosp, Dept Infect Dis & Infect Control, Yamagata, Japan

[10] Mae Fah Luang Univ Hosp, Dept Brain & Neurol, Chiang Rai, Thailand

[11] Mae Fah Luang Univ, Sch Integrat Med, Chiang Rai, Thailand

[12] Kasetsart Univ, Dept Comp Sci, Fac Sci, Bangkok, Thailand

[13] Mahidol Univ, Fac Med Technol, Dept Clin Microbiol & Appl Technol, Bangkok, Thailand

[14] Chulalongkorn Univ, Dept Physiol, Fac Med, Bangkok, Thailand

[15] Chulalongkorn Univ, Ctr Excellence Microcirculat, Fac Med, Bangkok, Thailand

[16] Fuling Ctr Hosp Chongqing City, Dept Gen Surg, Chongqing, Peoples R China

[17] Thammasat Univ, Chulabhorn Int Coll Med, Bangkok, Thailand

[18] Univ Bergen, Dept Clin Sci, Bergen, Norway

[19] Mahidol Univ, Fac Med Ramathibodi Hosp, Ctr Excellence, Dept Emergency Med, Bangkok, Thailand

[20] Gothenburg Univ, Sahlgrenska Acad, Dept Surg, Inst Clin Sci, S-40530 Gothenburg, Sweden

[21] SVKMs Narsee Monjee Inst Management Studies NMIMS, Sch Pharm & Technol Management, Hyderabad 509301, India

[22] Chulalongkorn Univ, Dept Microbiol, Translat Res Inflammat & Immunol Res Unit TRIRU, Bangkok, Thailand

[23] Yamagata Prefectural Cent Hosp, Dept Infect Dis & Infect Control, Pathogen Hunters Res Collaborat Team, Yamagata, Japan

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

INTENSIVE-CARE-UNIT; ANTIMICROBIAL SUSCEPTIBILITY; MULTIDRUG-RESISTANT; MECHANISMS; LIPOPOLYSACCHARIDE; PMRAB; IDENTIFICATION; CALCOACETICUS; POLYMYXINS;

D O I：

10.1038/s41598-022-15386-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Overcoming colistin-resistant Acinetobacter baumannii (CoR-AB) has become a major concern due to the lack of effective antibiotics. This study aimed to explore the prevalence of CoR-AB clinical isolates in Thailand, their mechanisms of resistance, and test the efficacy of colistin plus sulbactam against CoR-AB isolates. The colistin resistance rate among carbapenem-resistant A. baumannii was 15.14%. The mcr gene or its variants were not detected in CoR-AB isolates by PCR screening. The lipid A mass spectra of CoR-AB isolates showed the additional [M-H](-) ion peak at m/z = 2034 that correlated to the phosphoethanolamine (pEtN) addition to lipid A (N = 27/30). The important amino acid substitutions were found at position S14P, A138T, A227V in PmrB that are associated with overexpression of the pEtN transferase (PmrC) and contributed the pEtN addition. The lipopolysacccharide production genes (lpxACD) were not related to lipid A mass spectra. A colistin plus sulbactam combination exhibited the synergy rate at 86.7% against CoR-AB isolates compare to sulbactam (85.89% resistance) or colistin (15.14% resistance) alone. The excellent synergistic activity of colistin plus sulbactam combination has the potential for the treatment of CoR-AB infections.

引用

页数：13

共 42 条

[1] Resistance to Colistin in Acinetobacter baumannii Associated with Mutations in the PmrAB Two-Component System
Adams, Mark D.
Nickel, Gabrielle C.
Bajaksouzian, Saralee
Lavender, Heather
Murthy, A. Rekha
Jacobs, Michael R.
Bonomo, Robert A.
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (09) : 3628 - 3634
[2] The pmrCAB Operon Mediates Polymyxin Resistance in Acinetobacter baumannii ATCC 17978 and Clinical Isolates through Phosphoethanolamine Modification of Lipid A
Arroyo, Luis A.
Herrera, Carmen M.
Fernandez, Lucia
Hankins, Jessica V.
Trent, M. Stephen
Hancock, Robert E. W.
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2011, 55 (08) : 3743 - 3751
[3] Phosphoethanolamine Modification of Lipid A in Colistin-Resistant Variants of Acinetobacter baumannii Mediated by the pmrAB Two-Component Regulatory System
Beceiro, Alejandro
Llobet, Enrique
Aranda, Jesus
Antonio Bengoechea, Jose
Doumith, Michel
Hornsey, Michael
Dhanji, Hiran
Chart, Henrik
Bou, German
Livermore, David M.
Woodford, Neil
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2011, 55 (07) : 3370 - 3379
[4] Colistin, mechanisms and prevalence of resistance
Bialvaei, Abed Zahedi
Kafil, Hossein Samadi
[J]. CURRENT MEDICAL RESEARCH AND OPINION, 2015, 31 (04) : 707 - 721
[5] Complete Nucleotide Sequences of mcr-4.3-Carrying Plasmids in Acinetobacter baumannii Sequence Type 345 of Human and Food Origin from the Czech Republic, the First Case in Europe
Bitar, Ibrahim
Medvecky, Matej
Gelbicova, Tereza
Jakubu, Vladislav
Hrabak, Jaroslav
Zemlickova, Helena
Karpiskova, Renata
Dolejska, Monika
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2019, 63 (10)
[6] Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp enterica serovar Paratyphi B
Borowiak, Maria
Fischer, Jennie
Hammerl, Jens A.
Hendriksen, Rene S.
Szabo, Istvan
Malorny, Burkhard
[J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2017, 72 (12) : 3317 - 3324
[7] Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies
Cai, Yun
Chai, Dong
Wang, Rui
Liang, Beibei
Bai, Nan
[J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2012, 67 (07) : 1607 - 1615
[8] Clinical and Laboratory Standards Institute (CLSI), 2020, M100S26 CLSI
[9] Acinetobacter baumannii: Evolution of Antimicrobial Resistance-Treatment Options
Doi, Yohei
Murray, Gerald L.
Peleg, Anton Y.
[J]. SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE, 2015, 36 (01) : 85 - 98
[10] Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences
Falagas, Matthew E.
Athanasaki, Florentia
Voulgaris, Georgios L.
Triarides, Nikolaos A.
Vardakas, Konstantinos Z.
[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2019, 53 (01) : 22 - 28

← 1 2 3 4 5 →