A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii
Modification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant Acinetobacter baumannii. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transc...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66988 |
| _version_ | 1811180588260917248 |
|---|---|
| author | Jaeeun Park Misung Kim Bora Shin Mingyeong Kang Jihye Yang Tae Kwon Lee Woojun Park |
| author_facet | Jaeeun Park Misung Kim Bora Shin Mingyeong Kang Jihye Yang Tae Kwon Lee Woojun Park |
| author_sort | Jaeeun Park |
| collection | DOAJ |
| description | Modification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant Acinetobacter baumannii. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transcriptomic, and proteomic analyses revealed that upregulation of the pmr operon and decreased membrane-linkage proteins (OmpA, OmpW, and BamE) are linked to overproduction of OMVs, which also promoted enhanced biofilm formation. The addition of OMVs from PMB-resistant variants into the cultures of PMB-susceptible A. baumannii and the clinical isolates protected these susceptible bacteria from PMB. Taxonomic profiling of in vitro human gut microbiomes under anaerobic conditions demonstrated that OMVs completely protected the microbial community against PMB treatment. A Galleria mellonella-infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting A. baumannii from PMB. Taken together, OMVs released from A. baumannii functioned as decoys against PMB. |
| first_indexed | 2024-04-11T09:05:45Z |
| format | Article |
| id | doaj.art-1574fc4a4fec4cbd9b432919a4ceb69e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:45Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1574fc4a4fec4cbd9b432919a4ceb69e2022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.66988A novel decoy strategy for polymyxin resistance in Acinetobacter baumanniiJaeeun Park0Misung Kim1Bora Shin2Mingyeong Kang3Jihye Yang4Tae Kwon Lee5https://orcid.org/0000-0003-3845-7316Woojun Park6https://orcid.org/0000-0002-3166-1528Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaLaboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaLaboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaLaboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaLaboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaDepartment of Environmental Engineering, Yonsei University, Wonju, Republic of KoreaLaboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of KoreaModification of the outer membrane charge by a polymyxin B (PMB)-induced PmrAB two-component system appears to be a dominant phenomenon in PMB-resistant Acinetobacter baumannii. PMB-resistant variants and many clinical isolates also appeared to produce outer membrane vesicles (OMVs). Genomic, transcriptomic, and proteomic analyses revealed that upregulation of the pmr operon and decreased membrane-linkage proteins (OmpA, OmpW, and BamE) are linked to overproduction of OMVs, which also promoted enhanced biofilm formation. The addition of OMVs from PMB-resistant variants into the cultures of PMB-susceptible A. baumannii and the clinical isolates protected these susceptible bacteria from PMB. Taxonomic profiling of in vitro human gut microbiomes under anaerobic conditions demonstrated that OMVs completely protected the microbial community against PMB treatment. A Galleria mellonella-infection model with PMB treatment showed that OMVs increased the mortality rate of larvae by protecting A. baumannii from PMB. Taken together, OMVs released from A. baumannii functioned as decoys against PMB.https://elifesciences.org/articles/66988acinetobacter baumanniilps modificationsouter membrane vesiclcomponent regulatory systemsexperimental evolutionpolymyxin resistance |
| spellingShingle | Jaeeun Park Misung Kim Bora Shin Mingyeong Kang Jihye Yang Tae Kwon Lee Woojun Park A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii eLife acinetobacter baumannii lps modifications outer membrane vesicl component regulatory systems experimental evolution polymyxin resistance |
| title | A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii |
| title_full | A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii |
| title_fullStr | A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii |
| title_full_unstemmed | A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii |
| title_short | A novel decoy strategy for polymyxin resistance in Acinetobacter baumannii |
| title_sort | novel decoy strategy for polymyxin resistance in acinetobacter baumannii |
| topic | acinetobacter baumannii lps modifications outer membrane vesicl component regulatory systems experimental evolution polymyxin resistance |
| url | https://elifesciences.org/articles/66988 |
| work_keys_str_mv | AT jaeeunpark anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT misungkim anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT borashin anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT mingyeongkang anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT jihyeyang anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT taekwonlee anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT woojunpark anoveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT jaeeunpark noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT misungkim noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT borashin noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT mingyeongkang noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT jihyeyang noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT taekwonlee noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii AT woojunpark noveldecoystrategyforpolymyxinresistanceinacinetobacterbaumannii |